ProVee System for BPH

{0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Stent, Urethral, Prostatic, Permanent or Semi-Permanent Device Trade Name: ProVee System for BPH Device Procode: MER Applicant’s Name and Address: ProVerum Limited 2nd Floor Astor Hall, 4-8 Eden Quay, Dublin 1, D01 N5W8, Ireland Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P250011 Date of FDA Notice of Approval: December 9, 2025 II. INDICATIONS FOR USE The ProVee System for BPH is indicated for the treatment of obstructive lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH), in men with prostatic urethral lengths greater than or equal to 3.75 cm and prostatic volumes between 30 cc and 80 cc. III. CONTRAINDICATIONS Do not use the ProVee System for BPH in patients that have: - Urinary incontinence due to an incompetent external sphincter - Urethral pathologies that may prevent insertion of delivery system - An active symptomatic urinary tract infection - Current gross hematuria - Microscopic hematuria of unknown cause - Patients with known allergy to nickel or titanium - Presence of an existing stent in the urethral tract IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the ProVee System for BPH labeling. PMA P250011: FDA Summary of Safety and Effectiveness Data 1 of 48 {1} # V. DEVICE DESCRIPTION The ProVee System for BPH consists of the ProVee Expander (Figure 1) and Generation II Delivery System (Figure 2). The ProVee Expander is a nitinol implant that is preloaded in the Generation II Delivery System. The Generation II Delivery System is 16 Fr and has an irrigation feature to support visualization by allowing the user to clear debris from the field of view through the delivery of saline or deionized water. Both the ProVee Expander and Generation II Delivery System are single use sterile devices.  Figure 1: ProVee Expander  Figure 2: Generation II Delivery System The ProVee System for BPH is used alongside the ProVee Video Processing Unit (VPU) cleared under 510(k) K251734. The ProVee VPU (Figure 3) displays imaging from the Generation II Delivery System to allow the expander to be deployed under direct visualization. PMA P250011: FDA Summary of Safety and Effectiveness Data 2 of 48 {2}  Figure 3: ProVee VPU ## The ProVee Expander The ProVee Expander is intended to be permanently implanted. It has three apices intended to correspond with the three dominant lobes of the prostate. The ProVee Expander applies radial expansion force to the dominant lobes (two lateral lobes and the median lobe) of the prostate that grow with BPH. After the ProVee Expander is deployed, the gap between the wire struts prevents the obstruction of the verumontanum. The ProVee Expander is available in one size. ## Generation II Delivery System The Generation II Delivery System facilitates the targeted deployment of the ProVee Expander. The Generation II Delivery System is 16 Fr and consists of the delivery sheath, luer connector, delivery handle and external cable. The delivery sheath is the only direct patient contacting portion of the Generation II Delivery System. It is comprised of three sheaths: outer sheath, steering sheath, and camera sheath. The camera sheath consists of the camera tip with a CMOS imaging sensor, LEDs, and an irrigation channel. The Generation II Delivery System allows for staged, targeted deployment using control features that allow users to visualize the partially deployed ProVee Expander relative to the anatomical landmarks prior to full deployment. The Generation II Delivery System uses a transurethral approach. It also has a flexible steerable system, which allows the patient to be positioned in either supine or lithotomy position during the procedure. The Generation II Delivery System also has an irrigation feature to clear debris from the field of view to support visualization. ## ProVee Video Processing Unit (VPU) The VPU is a reusable accessory that is necessary for the use of the ProVee System for BPH. The ProVee VPU is intended to display live imaging data from the Generation II Delivery System. The ProVee VPU is a class II video processor cleared under 510(k) K251734. This device is not part of this PMA submission. PMA P250011: FDA Summary of Safety and Effectiveness Data 3 of 48 {3} The specifications of the ProVee System for BPH are provided in Table 1: | Table 1: Specifications for the ProVee System for BPH | | | --- | --- | | Item | Specification | | ProVee Expander dimensions | Length: 20.7 ± 0.5mm Internal Diameter: 18.62 ± 0.7mm | | Generation II Delivery System dimensions | Length of delivery sheath: 320 ± 2 mm Tip Outer Diameter: < 16 Fr | | Implant material | Medical grade Nitinol | ## VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the treatment of lower urinary tract symptoms attributed to BPH. According to the American Urological Association’s (AUA) guidelines (1), these alternatives include: ### Medical Therapy Medical therapy is typically the first treatment approach for BPH. Drug classes used to treat BPH include alpha blockers, 5-alpha reductase inhibitors, or a combination thereof, and phosphodiesterase-5 inhibitors. ### Surgical Therapy Surgical interventions for BPH include transurethral resection of the prostate (TURP), prostatectomy, transurethral incision of the prostate (TUIP), transurethral vaporization of the prostate (TUVP), photoselective vaporization of the prostate (PVP), prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), laser enucleation, robotic waterjet treatment (RWT), prostate artery embolization (PAE), and temporary and permanently implanted prostatic devices (TIPD). Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with their physician to select the method that best meets expectations and lifestyle. ## VII. MARKETING HISTORY The ProVee System for BPH has not been marketed in the United States or any foreign country. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device. - Dysuria - Hematuria - Micturition urgency PMA P250011: FDA Summary of Safety and Effectiveness Data 4 of 48 {4} - Urge incontinence - Pollakiuria - Penile pain - Bladder spasm - Nocturia - Painful ejaculation - Urethral pain - Urinary incontinence - Retrograde ejaculation - Constipation - Cystitis - Diarrhea - Hematospermia - Hypertonic bladder - Pelvic discomfort - Pelvic pain - Penile discomfort - Stress urinary incontinence - Testicular pain - Urinary tract infection (UTI) - Perineal pain - Muscle Spasms - Genital discomfort - Device dislocation (movement) For the specific adverse events that occurred in the clinical studies, please see Section X below. ## IX. SUMMARY OF NON-CLINICAL STUDIES ## A. Laboratory Studies ### 1. Bench Testing As described in Table 2, the applicant conducted the bench testing to evaluate the safety and performance of the ProVee System for BPH. The test results demonstrate that the ProVee System met all acceptance criteria. | Table 2: Summary of Bench Testing Performed on the ProVee System for BPH | | | | | --- | --- | --- | --- | | Test | Test Purpose | Acceptance Criteria | Results | | Implant Dimensional Verification | To verify dimensional specifications of the Expander wire, length, and diameter. | The Expander dimensions should meet dimensional specifications. | Pass | PMA P250011: FDA Summary of Safety and Effectiveness Data 5 of 48 {5} Table 2: Summary of Bench Testing Performed on the ProVee System for BPH | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Implant Af-Temperature Verification | To evaluate the Austenite finish temperature (Af) of the Expander per FDA recognized standard ASTM F2082/F2082M-16. | The Expander must have an Af temperature within the specified range. | Pass | | Implant Corrosion Testing | To evaluate the susceptibility of the Expander to corrosion per FDA recognized standard ASTM F2129-19a. | Testing shall indicate that the Expander is not susceptible to corrosion. Note: Per the FDA guidance document, Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol, issued in July 2021, if the corrosion study meets the specified acceptance criteria, and the surface finish approach is established, then a nickel ion release test is not warranted. | Pass | | Implant Durability | To assess the durability performance of the Expander per FDA recognized standard F3067-14. | Visual inspection of Expander patency under 10X magnification after 1 year of simulated use. The Exander must be patent with no implant fractures. | Pass | | Implant Strain Analysis/Fatigue Strain Limit and Factor of Safety | To evaluate the durability and integrity of the Expander using Finite Element Analysis (FEA) in simulated physiological conditions to calculate a fatigue factor of safety for the Expander per ASTM E739 and FDA recognized standard ASTM F3211. | Fatigue Safety Factor > 1 | Pass | | Implant Migration | To assess the migration potential of the Expander in a prostate model after 1 year of simulated use per FDA recognized standard F3067-14. | The Expander shall not migrate from the deployed position with no part of the implant in the bladder neck or external sphincter of the prostate model after 1-year simulated use under worst case physiological loading conditions. | Pass | PMA P250011: FDA Summary of Safety and Effectiveness Data 6 of 48 {6} Table 2: Summary of Bench Testing Performed on the ProVee System for BPH | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Implant Tensile Strength | To verify that the tensile performance of the implant exceeds the retrieval force. | The maximum force to retract the implant into the sheath is less than the minimum implant failure force. | Pass | | Implant Radial Expansion Force | To measure the radial expansion force of the Expander implant at minimum in vivo resting diameter and at maximum in vivo resting diameter. | The implant rests at a position/diameter at which a force equilibrium exists between the implant and prostate. | Pass | | Implant Crimping Force | To measure the force applied by the crimped implant to the inner diameter of the outer sheath of the delivery device. | At a minimum inner diameter of the outer sheath of the delivery device, the implant shall have a crimp force within a specified range. | Pass | | Delivery System Functionality | To demonstrate that the Expander can be accurately placed in a simulated use model by evaluating each step of the Expander delivery process. | The delivery system shall deliver the Expander to the intended location and maintain its integrity. | Pass | | Delivery System Maximum Insertion Width | To measure the maximum insertion width of the ProVee System for BPH. | Tip of the ProVee System for BPH <16.5 Fr (5.5mm). | Pass | | Delivery System Image Quality | To demonstrate image quality of the ProVee System for BPH visualization features. | Image quality features of the delivery system must meet specified criteria. | Pass | | Delivery System Image Latency | To measure the latency of the ProVee System for BPH. | Image latency must be within the allowable range. | Pass | | Delivery System Handle Ergonomics | To verify the ProVee System for BPH handle dimensions allow the handle to be held one handed and compressed to fully deploy the Expander per ergonomic hand grip data | The delivery system dimensions must be within the allowable range. | Pass | | Delivery System Integrity | To challenge the functional integrity of the ProVee System for BPH under irrigation by subjecting it to worst-case loading in simulated clinical use. | The delivery system shall withstand specified forces and maintain its integrity. | Pass | PMA P250011: FDA Summary of Safety and Effectiveness Data 7 of 48 {7} | Table 2: Summary of Bench Testing Performed on the ProVee System for BPH | | | | | --- | --- | --- | --- | | Test | Test Purpose | Acceptance Criteria | Results | | Delivery System Irrigation Flow Rate | To verify the minimum irrigation flow rate of the delivery device per FDA recognized standard ISO 20696: 2018. | The delivery system shall have an average flow rate that is greater than or equal to the specified minimum flow rate. | Pass | | Delivery System Characterization of Maximum Deflection (Fatigue Testing) | To measure the maximum upwards deflection angle in stage 0 across cycles per FDA recognized standard ISO 8600-1: 2015. | The maximum deflection angle must be greater than or equal to the minimum specification for the maximum deflection angle. | Pass | | Delivery System Tensile Strength (Camera Sheath and Outer Sheath Integrity) | To evaluate the tensile strength of the delivery system bonds. | The delivery system bonds must meet the establish acceptance criteria for integrity. | Pass | The applicant also conducted the following optical and color performance testing for the Delivery System: - Photobiological Safety: The photobiological safety of the subject device was evaluated according to IEC 62471:2006 using measurement distances of 200 and 0 mm. The results of testing indicate the subject device is not expected to pose a photobiological safety risk to patients or operators. - Field of View (FOV) and Direction of View (DOV): The FOV and DOV were evaluated based on the distance between the entrance pupil and the target (Method B of ISO 8600-3:2019). The subject device met the FOV and DOV specifications. - Resolution and Depth of Field (DOF): The applicant evaluated the resolution characteristics of the delivery system based on modulation transfer function (MTF). The DOF was evaluated by measuring the MTF at the center of the FOV from near (3 mm) to far (50 mm) working distance. The resolution at the center and 70% FOV was also evaluated. The subject device met the DOF and MTF specifications. - Geometric Distortion: Geometric distortion of the delivery device was characterized using geometric distortion versus image radius curves. The geometric distortion of the subject device was adequately characterized and is acceptable. - Noise and Dynamic Range: The signal-to-noise (SNR) and dynamic range was evaluated according to ISO 15739: 2023. The subject device SNR and dynamic range values were acceptable. - Image Intensity Uniformity (IIU): The IIU of the delivery device was evaluated by imaging a diffuse reflectance target illuminated only with the device's light source. The IIU was adequately characterized and is acceptable. PMA P250011: FDA Summary of Safety and Effectiveness Data 8 of 48 {8} - Color Performance: The applicant evaluated the color performance of the subject device by positioning the subject device at a prespecified distance from the color target and illuminating the target only with the device's own light source. Optical measurements were taken from the color target (ground truth) and device display (reproduced data) to analyze the ability of the subject device to reproduce color and preserve color contrast. The results demonstrate the device has adequate color performance. ## 2. Biocompatibility Biocompatibility testing was performed for all patient-contacting components of the ProVee System for BPH in accordance with FDA Guidance Document, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process", issued in September 2023. The following biocompatibility endpoints were assessed: - The ProVee Expander is categorized as an implant device, contacting tissue for permanent duration (&gt;30 days). - Cytotoxicity (ISO 10993-5:2009) - Sensitization (ISO 10993-10:2021) - Intracutaneous Irritation (ISO 10993-23:2021) - Acute systemic toxicity (ISO 10993-11:2017) - Material mediated pyrogen (ISO 10993-11: 2017) - 4, 13-week subacute/subchronic systemic toxicity following implantation (ISO 10993-11:2017) - 4, 13-week intramuscular implantation (ISO 10993-6:2016) - Genotoxicity testing (ISO 10993-3:2014) - Chemical characterization (ISO 10993-18:2020) followed by Toxicological Risk Assessment 10993-17:2023) to evaluate genotoxicity, chronic systemic toxicity, carcinogenicity, and developmental/reproductive toxicity. - The Generation II Delivery System is categorized as a limited contact device with intact mucosal membrane (&lt;24 hours). - Cytotoxicity (ISO 10993-5:2009) - Sensitization (ISO 10993-10:2021) - Intracutaneous Irritation (ISO 10993-23:2021) The results of biocompatibility testing demonstrated that all patient-contacting components of the ProVee System for BPH are biocompatible. ## 3. Sterility/Shelf-Life/Reprocessing The ProVee Expander is preloaded in the Gen II Delivery System, and both components are single use sterile devices. The ProVee System for BPH is PMA P250011: FDA Summary of Safety and Effectiveness Data 9 of 48 {9} sterilized by ethylene oxide (EO) gas to an assurance level (SAL) of $10^{-6}$ per ISO 11135:2014. The applicant tested the ProVee System for BPH for EO residuals in conformance with ISO 10993-7:2008 to ensure that maximum residual levels of EO and ethylene chlorohydrin (ECH) remaining on the ProVee System for BPH after sterilization do not exceed the recommended limits for medical devices with permanent patient contact. The shelf-life for the ProVee System for BPH is established at 12 months based on an accelerated aging study conducted on ProVee System for BPH. To support the 12 months shelf life, package integrity and functional testing were conducted. Package integrity was validated in accordance with ISO 11607-1:2019. Packages were inspected for visual inspection (ASTM F1886/F188M-16), seal strength (ASTM F88/F88M-21), and leakage testing by bubble test (ASTM F2096-19). The functional testing conducted after accelerated aging is described in Table 2 above. The results demonstrated that ProVee System for BPH has acceptable package integrity and functional performance over the duration of its 12-month shelf life. ## 4. Electromagnetic Compatibility &amp; Electrical Safety The applicant conducted electromagnetic compatibility and electrical safety testing on the ProVee System for BPH in accordance with the following standards: - IEC 60601-1:2005 + A2: 2020, Medical Electrical Equipment, General requirements for safety - Collateral standard: Safety requirements for medical electrical systems - IEC 60601-2-18:2009, Medical electrical equipment - Part 2-18: Particular requirements for the basic safety and essential performance of endoscopic equipment - IEC 60601-1-2:2020, Medical electrical equipment – Part 1-2: General requirements for basic safety and essential performance – Collateral standard: Electromagnetic disturbances – Requirements and tests The ProVee System for BPH passed electrical safety and electromagnetic compatibility testing consistent with the acceptance criteria outlined in these standards. The applicant provided adequate labeling instructions related to the electrical safety and electromagnetic compatibility of the ProVee System for BPH. ## 5. Magnetic Resonance (MR) Compatibility The applicant conducted MRI compatibility testing on the ProVee System for BPH to verify that it can be used in MRI environments (of 1.5 Tesla and 3.0 PMA P250011: FDA Summary of Safety and Effectiveness Data 10 of 48 {10} Tesla). The testing was conducted in accordance with the following FDA recognized standards: ASTM F2052-21, ASTM F2182-19e2, ASTM F2503-23 and ASTM F2213-17. The results demonstrated that ProVee System for BPH is MR Conditional under conditions specified on the labeling. ## B. Animal Studies The applicant conducted an animal study to determine the safety and effectiveness of the ProVee Expander prior to clinical testing. A 6-month GLP large animal study was conducted in a healthy, intact male canine model for evaluation of implant migration, encrustation, erosion, pressure necrosis, urothelial hyperplasia/tissue ingrowth, stone formation, urethral edema, cellular atypia, and device failure or breakage. The study included 6 male dogs assigned to the test article group and 2 male dogs to the sham procedure group. Due to anatomical limitations, the implant was surgically deployed anterograde from the bladder into the prostatic urethra, rather than retrograde as clinically intended. The study demonstrated successful deployment, patency of the prostatic urethra, implant durability, with no encrustation, erosion or perforation. The animal study supported long term in vivo safety of the ProVee Expander. FDA accepted the 6-month study duration, the minimum considered for this device type, because the supportive safety data raised no concerns that would warrant a longer evaluation. Similarly, the small cohort size (n=2) for the sham procedure group was deemed acceptable due to limited variability of data and the absence of unexpected early mortality. ## X. SUMMARY OF PRIMARY CLINICAL STUDY(IES) The applicant completed three (3) clinical studies as follows: 1. ProVerum "First in Man" PROVE Study – This was a feasibility study for the ProVee System for BPH. 2. ProVIDE Study (G210344) – This was the pivotal clinical study for the ProVee System for BPH. 3. ProVIDE II Bridging study (G230354) – This study evaluated a new version the delivery system, the Gen II Delivery System. ### 1. "First in Man" Study (PROVE Study) The applicant conducted a prospective, non-randomized, single center feasibility clinical study between May 2019 and November 2019 at an investigational site in Australia to evaluate the ProVee System for BPH. Men ≥ 50 years with moderate-to-severe symptomatic BPH, International Prostate Symptom Score (IPSS) of &gt; 15, peak urinary flow rate (Qmax) of &lt; 12 mL/s, prostate volume of ≥ 30 and ≤ 80 cc, and prostatic urethral lengths ≥ 4 cm were the target population. Ten subjects were enrolled, were PMA P250011: FDA Summary of Safety and Effectiveness Data 11 of 48 {11} implanted with the ProVee Expander and completed the study follow-up visits. The patients were followed up to 24 months after the procedure. Of the 10 implanted subjects, 12 total adverse events (AEs) were reported in 7 of the implanted subjects. There were no device or procedure related serious AEs or unanticipated adverse device effects (UADEs). All but one AE resolved within 24-month follow-up period. There was 100% technical success in the deployment of the implant. There were no procedural complications, all patients voided post procedure, and no patients required post-operative catheterization. At 24-months, there was a 40% improvement from baseline in Qmax and men not on LUTS medication prior to the procedure showed an average improvement from baseline in IPSS of 37%. There were no surgical re-treatments through 24-months. ## 2. Pivotal Clinical Study (ProVIDE Study) The applicant performed a pivotal clinical study to establish reasonable assurance of safety and effectiveness of the ProVee System for BPH in treatment of obstructive lower urinary tract symptoms secondary to BPH in the US, Ireland, and Canada under IDE# G210344. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ## A. Study Design Patients were implanted with the ProVee Expander between June 9, 2022, and March 15, 2024. The database for this PMA reflected data collected through March 5, 2025 and included 221 patients. There were 17 investigational sites. The study was a prospective, multi-center, double-blind, 2:1 randomized, sham controlled, clinical study. Subjects in both arms were blinded for 3 months following PMA P250011: FDA Summary of Safety and Effectiveness Data 12 of 48 {12} implantation. At 3 months, patients in the sham arm could elect to crossover into the device arm. All subjects were then followed up through 60 months. The control group was a sham treatment in which a ureteroscope was placed through an access sheath without deployment of an implant. 1. Clinical Inclusion and Exclusion Criteria Enrollment in the ProVIDE study was limited to patients who met the following inclusion criteria: 1) Males ≥ 45 years of age 2) IPSS of ≥ 13, IPSS V/S ≥ 1 at baseline assessment 3) Prostate volume of ≥ 30 cc and ≤ 80 cc 4) Prostatic urethral L2 lengths ≥ 3.75cm by transrectal ultrasound (TRUS) 5) Failed, intolerant, or subject choice to not take a medication regimen for the treatment of lower urinary tract symptoms (LUTS) Patients were not permitted to enroll in the ProVIDE study if they met any of the following exclusion criteria: 1) Void volume ≤ 125 ml; Qmax ≥ 12ml/s; PVR &gt; 250 ml 2) Obstructive median lobe defined by EITHER &gt;10mm protrusion on sagittal mid-prostate plane as measured by TRUS OR an obstructive median lobe seen on cystoscopy e.g., 'ball valve' 3) High bladder neck, with the absence of lateral lobe encroachment indicating a high likelihood of primary bladder neck obstruction 4) Anatomy that would prevent the apices of the ProVee Expander from engaging with the lateral lobes; e.g., high degree of bladder neck angulation such that the anterior bladder neck is not visible 5) Acute urinary retention 6) Known immunosuppression 7) History of or suspected prostate or bladder cancer 8) Baseline prostate specific antigen (PSA) &gt; 10 ng/mL or confirmed or suspected prostate cancer (Subjects with a PSA level above 2.5 ng/mL, or age specific, or local reference ranges should have prostate cancer excluded to the Investigator's satisfaction, including a standard of care (SOC) biopsy if indicated) 9) Recent urinary tract stones OR widespread calcifications on the prostatic urethral wall, within 3 months of index procedure 10) A history of prostatitis within the last two years 11) Active or history of epididymitis within the past 3 months 12) Neurogenic bladder and/or sphincter abnormalities due to Parkinson's disease, multiple sclerosis, cerebral vascular accident, diabetes. 13) History of urinary retention within 12 months of baseline assessment 14) Requiring self-catheterization to void 15) An active urinary tract infection (UTI) at time of index procedure PMA P250011: FDA Summary of Safety and Effectiveness Data 13 of 48 {13} 16) Gross hematuria, within 3 months of index procedure 17) Subjects with known allergy to nickel or titanium 18) Life expectancy estimated to be less than 60 months 19) Taking androgens, unless eugonadal state for at least 3 months or greater with a stable dosage for at least 2 months as documented by the Investigator 20) Use of 5-alpha-reductase inhibitors (e.g., dutasteride, finasteride) within 6 months of baseline assessment 21) Use of Phenylephrine / Pseudoephedrine within 24 hours of baseline assessment 22) Use of alpha-blockers (e.g., Terazosin, Doxazosin, Alfuzosin, Tamsulosin) within 2 weeks of baseline assessment 23) Use of estrogen or drug-producing androgen suppression (e.g. gonadotropin-releasing hormonal analogues) within 1 year of baseline assessment 24) Use of antihistamines, anticonvulsants, and antispasmodics within 1 week of baseline assessment unless there is documented evidence that the patient was on the same drug dose for at least 6 months with a stable voiding pattern (the drug dose should not be altered or discontinued for entrance into or throughout the study) 25) Use of anticholinergics or cholinergic medication within 2 weeks of baseline assessment 26) Use of beta-blockers where the dose is not stable. (Stable dose is defined as having the same medication and dose in the last 6 months) 27) Use of Phosphodiesterase-5 Enzyme Inhibitors in doses for BPH within 2 weeks of baseline assessment 28) Current treatment with anticoagulants (e.g., coumadin or enoxaparin) or antiplatelet medications other than aspirin (e.g., clopidogrel, or alternative and ASA). Patient unable to stop taking anticoagulants and/or antiplatelets within 3 days prior to the procedure or coumadin at least 5 days prior to the procedure. Low dose aspirin ≤100mg/day not prohibited 29) Future fertility concerns 30) Previous prostate surgery, balloon dilatation, stent implantation, laser prostatectomy, hyperthermia, or any other invasive treatment to the prostate; including penile implants 31) Previous pelvic irradiation or radical pelvic surgery 32) Previous rectal surgery (other than hemorrhoidectomy) or known history of rectal disease 33) Urethral strictures, bladder neck contracture, or other potentially confounding bladder pathology 34) Urethral pathologies that may prevent insertion of Delivery System 35) Uncontrolled diabetes mellitus including Hgb AIC &gt;8% 36) Overactive bladder (OAB) requiring treatment by OAB medication PMA P250011: FDA Summary of Safety and Effectiveness Data 14 of 48 {14} 37) Urinary incontinence 38) Patients taking tri-cyclic antidepressants 39) Compromised renal function (i.e., serum creatinine &gt;1.8 mg/dl or upper tract disease) 40) Hepatic disorder, bleeding disorders or metabolic impairment that might confound the results of the study or have a risk to subject per investigator's opinion 41) Any major comorbidities or presence of unstable conditions, e.g., uncontrolled HTN, NYHA Class III or IV, cardiac arrhythmias that are not controlled by medication/medical device, myocardial infarction within the past 6 months, COPD with FEV1 &lt; 50, renal illness that might prevent study completion or would confound study results 42) Vulnerable populations such as incarcerated or institutionalized adults, inmates, patients with physical, psychological (such as developmentally delayed adults), or medical impairment that might, in the judgment of the Investigator, prevent study completion or comprehension, or may confound study results (including patient questionnaires) 43) History or current medical condition that would result in an unacceptable patient risk if that subject were to be included in the study 44) Any subject that is currently enrolled in another ongoing investigational study 2. Follow-up Schedule All subjects were scheduled to return for follow-up examinations at 1 month, 3 months, 6 months, and 12 months postoperatively. Subjects will continue to be followed up annually through 5 years. Preoperatively, the following assessments were completed for during study screening: physical exam and measuring vital signs, International Prostate Symptom Score (IPSS) and Quality of Life (QoL) questionnaires, the abridged International Index of Erectile Function -5 (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Dysfunction (MSHQ-EjD), Face Pain Scale-Revised (FPS-R), Uroflowmetry, Post Void Residual Volume (PVR), Prostate-specific antigen (PSA), Complete blood count (CBC), Renal Function, Transrectal ultrasound (TRUS), cystoscopy and concomitant medications. Postoperatively, the assessments completed included the International Prostate Symptom Score (IPSS) and Quality of Life (QoL) questionnaires, the abridged International Index of Erectile Function -5 (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Dysfunction (MSHQ-EjD), Face Pain Scale- PMA P250011: FDA Summary of Safety and Effectiveness Data 15 of 48 {15} Revised (FPS-R), Uroflowmetry, Post Void Residual Volume (PVR), Cystoscopy (at 1 year follow-up only) and concomitant medications. Adverse events and complications were recorded at all visits. The key timepoints are shown below in the tables summarizing safety and effectiveness. ## 3. Clinical Endpoints With regards to safety, the primary safety endpoints included the following: - the rate of device or procedure related serious adverse events were evaluated through 12-months - the rate of extended post-operative urinary catheterization (&gt;7 days from treatment) for inability to void among patients treated with the ProVee Expander The secondary safety endpoints including the following: - Rate of device or procedure related adverse events at all time points. - Comparison pain at discharge to 1, 3, 6 and 12-month follow-up visits per Faces Pain Scale-Revised Questionnaire (FPS-R). - Change in sexual health characterized by change in the International Index of Erectile Function, specifically the Erectile Function domain (IIEF-5) and Male Sexual Health Questionnaire- Ejaculatory Domain (MSHQ-EjD) at 3, 6 and 12 - month post treatment. - Proportion of subjects with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability evidenced through 3-month follow-up visit. - Assessment of retrieval procedure related adverse events related to implant removal. With regards to effectiveness, the co-primary effectiveness endpoints were as follows: - Reduction in BPH symptoms compared to sham at 3 months compared to baseline as measured by IPSS. The mean 3-month improvement from baseline score for IPSS for the ProVee arm should demonstrate a minimum statistical margin of 25% compared to mean improvement from baseline for IPSS for the Sham arm. - Symptom improvement by measurement of mean percent change in IPSS at 12 months compared to baseline. The mean percent change from baseline in IPSS at 12-months post-implant for the ProVee arm Group is less than -30%. The secondary effectiveness endpoints included the following: - Percent of subjects who experience at least a 30% improvement in IPSS from their baseline pre-treatment score at 1, 3, 6 and 12 - month post treatment. PMA P250011: FDA Summary of Safety and Effectiveness Data 16 of 48 {16} - Percent change in IPSS in the treatment arm compared to baseline at all timepoints post treatment. - Mean improvement from baseline in QoL questionnaire at 3, 6, 12-month follow-up visits. - Mean improvement from baseline in uroflowmetry measures of peak flow rate (Qmax) as measured at all timepoints. - Mean improvement from baseline in PVR as measured at all timepoints. - Post-procedure incidence of secondary reintervention using alternate surgical LUTS therapy. - Post-procedure incidence of secondary reintervention using prescribed pharmacological agents for BPH LUTS therapy. With regard to success/failure criteria, an individual patient was considered an IPSS responder if their IPSS score improved by at least 30% at 12 months compared to baseline. The study was considered a success if both co-primary effectiveness endpoints were met, and the device had an acceptable safety profile. ## B. Accountability of PMA Cohort At the time of database lock, of 221 patients enrolled in the PMA study, 201 patients (91%) were available for analysis at the 12-month post-operative visit. Patients were considered enrolled after signing the informed consent form and meeting all the inclusion criteria and none of the exclusion criteria. Eleven subjects in the ProVee treatment arm and 7 subjects in the Sham arm exited the study before the 12-month follow-up. In the ProVee treatment arm, one subject did not receive a ProVee device, one subject was lost to follow-up, one subject died (adjudicated by CEC as unrelated to either the ProVee device or the study procedure); two subjects withdrew due to unwillingness to participate in the trial; three subjects were withdrawn by the study investigator (patients were not happy with their symptom improvement and requested device removal); and three subjects due to drug re-intervention. In the sham arm, one subject was lost to follow up, 6 PMA P250011: FDA Summary of Safety and Effectiveness Data 17 of 48 {17} subjects elected not to cross over. The subject disposition for the study through 12 months is provided in Figure 4:  Figure 4: Subject Accountability Flow Chart The analysis sets were pre-specified in the protocol as follows: Intent-to-Treat cohort (ITT): All eligible subjects who are randomized and who had the implant deployed during the index procedure are included in the ITT regardless of outcome. Per Protocol Cohort (PP): The PP cohort is defined as the group of subjects who complete the treatment procedure and who complete their 3-month follow-up visit without any protocol violations. Safety Cohort: The safety population is the same as the ITT population. Analyses of all primary and secondary effectiveness endpoints were completed for the safety/ITT cohort and for the PP cohort. Study success was based on safety/ITT cohort. Analyses for all safety-related endpoints were performed using the safety/ITT cohort. ## C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a BPH study performed in the US. PMA P250011: FDA Summary of Safety and Effectiveness Data 18 of 48 {18} The demographic information for the subjects enrolled in the study are provided in Table 3. The demographics and baseline characteristics are well matched between the ProVee and sham arms. | Table 3: Subject Demographics | | | | | | --- | --- | --- | --- | --- | | Characteristic | ProVee (N=150) | Sham (N=71) | Crossover (N=64) | Total (N=221) | | Age | 64.0 (150) | 64.5 (71) | 64.3 (64) | 64.1 (221) | | Race | | | | | | American Indian or Alaska Native | 0.0% (0/150) | 0.0% (0/71) | 0.0% (0/64) | 0.0% (0/221) | | Asian | 1.3% (2/150) | 0.0% (0/71) | 0.0% (0/64) | 0.9% (2/221) | | Black or African American | 5.3% (8/150) | 1.4% (1/71) | 1.6% (1/64) | 4.1% (9/221) | | Hawaiian or Pacific Islander | 0.0% (0/150) | 0.0% (0/71) | 0.0% (0/64) | 0.0% (0/221) | | White | 91.3% (137/150) | 95.8% (68/71) | 95.3% (61/64) | 92.8% (205/221) | | Multi-Racial | 0.7% (1/150) | 0.0% (0/71) | 0 (0/64) | 0.5% (1/221) | | Other | 1.3% (2/150) | 1.4% (1/71) | 1.6% (1/64) | 1.4% (3/221) | | Not Collected | 0.0% (0/150) | 1.4% (1/71) | 1.6% (1/64) | 0.5% (1/221) | | Ethnicity | | | | | | Hispanic or Latino | 12.7% (19/150) | 8.5% (6/71) | 9.4 % (6/64) | 11.3% (25/221) | | Not Hispanic or Latino | 85.3% (128/150) | 88.7% (63/71) | 87.5 % (56/64) | 86.4% (191/221) | | Not Collected | 2.0% (3/150) | 2.8% (2/71) | 3.1 % (2/64) | 2.3% (5/221) | The baseline prostate characteristics and LUTS severity for the ITT population are provided in Table 4. The baseline prostate characteristics and LUTS severity are well matched between the ProVee and sham arms. | Table 4: Baseline Prostate Characteristics and LUTS Severity | | | | | | --- | --- | --- | --- | --- | | Characteristic | ProVee (N=150) | Sham (N=71) | Cross over (N = 64) | Total (N=221) | | BMI | 28.1 ± 4.4 (150) | 28.5 ± 5.8 (71) | 28.1 ± 4.7 (64) | 28.2 ± 4.9 (221) | | Prostate Volume (mL) | 47.1 ± 14.0 (150) | 49.5 ± 12.9 (71) | 50.6 ± 12.9 (64) | 47.8 ± 13.7 (221) | | Prostatic Urethral Length (cm) | 4.9± 0.6 (150) | 4.9 ± 0.6 (71) | 4.9 ± 0.6 (64) | 4.9 ± 0.6 (221) | PMA P250011: FDA Summary of Safety and Effectiveness Data 19 of 48 {19} | IPSS Score | 24.6 ± 5.0 (150) | 23.4 ± 5.4 (71) | 23.5 ± 5.3 (64) | 24.2 ± 5.1 (221) | | --- | --- | --- | --- | --- | | IPSS V/S Score | 1.5 ± 0.5 (150) | 1.5 ± 0.5 (71) | 1.4 ± 0.4 (64) | 1.5 ± 0.5 (221) | | Qmax (mL/sec) | 8.8 ± 2.0 (150) | 8.8 ± 2.2 (71) | 8.9 ± 2.2 (64) | 8.8 ± 2.1 (221) | | Post Void Residual (mL) | 57.3 ± 59.4 (150) | 59.3 ± 55.4 (71) | 61.5 ± 57.1 (64) | 57.9 ± 58.0 (221) | | PSA (ng/mL) | 2.3 ± 1.8 (150) | 2.6 ± 2.1 (71) | 2.8 ± 2.2 (64) | 2.4 ± 1.9 (221) | ## D. Safety and Effectiveness Results ### 1. Safety Results The analysis of safety was based on the ITT cohort of 221 patients (71 sham subjects and 150 ProVee treatment subjects) available for the 12-month evaluation. The key safety outcomes for this study are presented in Tables 5 to 10. No subjects required extended post-operative urinary catheterization (&gt;7 days from treatment). A total of 319 AEs were reported in 126 subjects (57%) including 8 serious adverse events (SAEs). No reported SAEs were adjudicated by the Clinical Events Committee (CEC) as device or procedure related. The SAEs observed in the treatment arm are listed in Table 6. As reported in Table 7, of the 298 AEs reported in the ProVee treatment arm, the CEC adjudicated 71 AEs in 39 subjects as probable or highly probable device and/or procedure related. Thirty-three AEs in 18 subjects were adjudicated as device related. Fifty-one AEs in 31 subjects were adjudicated as procedure related. The device and/or procedure related AEs were typically mild, transient and commonly associated with urological procedures. One AE was classified as Clavien-Dindo Grade IIIb or higher (squamous cell carcinoma on the tongue 84 days post index procedure). This was adjudicated as unrelated to the device or procedure. As reported in Table 7a and b, a total of 14 (19.7%) subjects in the sham arm experienced a total of 21 AEs. There were no SAEs in the sham arm and a total of 21 non-SAEs in 14 (19.7%) subjects. There were no device related AEs in the Sham arm and 6 procedure related AEs in 5 (7%) subjects. All the device/procedure related AEs were mild, transient and typically associated with urological procedures. As reported in Table 7a and b, 32 out of the 33 device related AEs and 50 out of the 51-procedure related AEs in the ProVee treatment arm occurred within 3- PMA P250011: FDA Summary of Safety and Effectiveness Data 20 of 48 {20} months of the procedure, with 92% of the events (65 out of 71) occurring within the first 3 weeks post procedure. Table 7c lists the AEs in the crossover arm. The AEs observed in the crossover arm are similar to those observed in the ProVee arm. | Table 5: Summary of Adverse Events (ITT Population) | | | | | | --- | --- | --- | --- | --- | | Event Types | ProVee Arm | | Sham Arm | | | | Subjects n (%) | Events n | Subjects n (%) | Events n | | Any adverse event | 112 (74.7) | 298 | 14 (19.7) | 21 | | Serious adverse events | 5 (3.3) | 8 | 0 | 0 | | Non serious adverse events | 107 (96.7) | 290 | 14 (19.7) | 21 | | Treatment Related Adverse Events | | | | | | Device Related | 18(12.0) | 33 | 0 | 0 | | Procedure Related | 31(20.7) | 51 | 5 (7.0) | 8 | | Table 6: Summary of Serious Adverse Events (ITT Population) | | | --- | --- | | Serious Adverse Events | Events (n) | | Small bowel obstruction | 1 | | Prostate cancer | 1 | | Transient ischemic attack | 1 | | Cerebrovascular accident | 1 | | Squamous cell carcinoma | 1 | | Cellulitis | 1 | | Pancreatic carcinoma metastatic | 1 | | Sepsis | 1 | | Table 7a: Summary of Device Related Adverse Events (ITT Population) | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event | ProVee Arm 0-3 Months | | Sham Arm 0-3 Months | | ProVee Arm 3-12 Months | | | | No. Events | No. Subjects (%) | No. Events | No. Subjects (%) | No. Events | No. Subjects (%) | | Dysuria | 7 | 7 (4.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Hematuria | 6 | 6 (4.0%) | 0 | 0 (0.0%) | 1 | 1 (0.7%) | | Micturition Urgency | 4 | 4 (2.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Urge Incontinence | 2 | 2 (1.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Bladder Spasm | 2 | 2 (1.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Penile Pain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Pollakiuria | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Nocturia | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Painful ejaculation | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | PMA P250011: FDA Summary of Safety and Effectiveness Data 21 of 48 {21} | Table 7b: Summary of Procedure Related Adverse Events (ITT Population) | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Adverse Event | ProVee Arm 0-3 Months | | Sham Arm 0-3 Months | | ProVee Arm 3-12 Months | | | | No. Events | No. Subjects (%) | No. Events | No. Subjects (%) | No. Events | No. Subjects (%) | | Dysuria | 9 | 9 (6.0%) | 1 | 1 (1.4%) | 0 | 0 (0.0%) | | Hematuria | 7 | 7 (4.7%) | 2 | 2 (2.8%) | 0 | 0 (0.0%) | | Urge Incontinence | 4 | 4 (2.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Pollakiuria | 4 | 4 (2.7%) | 2 | 1 (1.4%) | 0 | 0 (0.0%) | | Penile pain | 3 | 3 (3.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Bladder spasm | 3 | 3 (3.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Micturition urgency | 2 | 2 (1.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Urinary incontinence | 2 | 2 (1.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Retrograde ejaculation | 2 | 2 (1.3%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Nocturia | 1 | 1 (0.7%) | 1 | 1 (1.4%) | 0 | 0 (0.0%) | | Painful ejaculation | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Urethral pain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Penile discomfort | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Hematospermia | 1 | 1 (0.7%) | 1 | 1 (1.4%) | 0 | 0 (0.0%) | | Constipation | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Cystitis | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Diarrhea | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Hypertonic bladder | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Pelvic pain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Stress urinary incontinence | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Testicular pain | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Urinary tract infection | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Muscle spasms | 1 | 1 (0.7%) | 0 | 0 (0.0%) | 0 | 0 (0.0%) | | Genital discomfort | 0 | 0 (0.0%) | 1 | 1 (1.4%) | 0 | 0 (0.0%) | PMA P250011: FDA Summary of Safety and Effectiveness Data 22 of 48 {22} | Device dislocation | 0 | 0 (0.0%) | 0 | 0 (0.0%) | 1 | 1 (0.7%) | | --- | --- | --- | --- | --- | --- | --- | | Total Related AEs | 50 | 31 (20.7%) | 8 | 5 (7.0%) | 1 | 1 (0.7%) | <br/> | Table 7c: Summary of Adverse Events in Crossover Arm | | | | | | --- | --- | --- | --- | --- | | Adverse Event | Cross Over (N=64) 0-3 Months | | Cross Over (N=64) 3-12 Months | | | | No. Events | No. Subjects (%) | No. Events | No. Subjects (%) | | Dysuria | 14 | 7 (10.9%) | 0 | 0 (0.0%) | | Micturition urgency | 14 | 7 (10.9%) | 0 | 0 (0.0%) | | Hematuria | 12 | 6 (9.4%) | 0 | 0 (0.0%) | | Bladder spasm | 6 | 3 (4.7%) | 0 | 0 (0.0%) | | Painful ejaculation | 6 | 3 (4.7%) | 0 | 0 (0.0%) | | Urinary incontinence | 4 | 2 (3.1%) | 0 | 0 (0.0%) | | Hematospermia | 4 | 2 (3.1%) | 0 | 0 (0.0%) | | Stress urinary incontinence | 4 | 2 (3.1%) | 0 | 0 (0.0%) | | Urge incontinence | 2 | 1 (1.6%) | 0 | 0 (0.0%) | | Pollakiuria | 2 | 1 (1.6%) | 0 | 0 (0.0%) | | Penile pain | 2 | 1 (1.6%) | 0 | 0 (0.0%) | | Perineal pain | 2 | 1 (1.6%) | 0 | 0 (0.0%) | | Total Related AEs | 72 | 24 (37.5%) | 0 | 0 (0%) | As reported in Table 8, the study also evaluated pain between the treatment and sham arm as a secondary safety endpoint. No difference in the pain assessment PMA P250011: FDA Summary of Safety and Effectiveness Data 23 of 48 {23} between the two groups were observed. The pain assessment score between the two arms at baseline and discharge had a mean value of 1 ("barely noticeable"). | Table 8: FPS-R Pain Scores Post Procedure through 12-months (ITT Population) | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Group | Baseline | Discharge | 1-Month | 3-Months | 6-Months | 12-Months | | ProVee Arm n | 150 | 150 | 150 | 147 | 144 | 141 | | Mean (SD) | 1.0±1.8 | 1.0±1.78 | 0.9±1.77 | 1.1±2.0 | 0.9±1.8 | 0.8±1.7 | | Sham Arm n | 70 | 71 | 70 | 70 | -- | -- | | Mean (SD) | 1.0±1.8 | 1.1±2.0 | 0.5±1.4 | 0.4±1.3 | -- | -- | As reported in Table 9 and Table 10, the secondary safety endpoints also included the evaluation of sexual health at 3 months post procedure through 12-months post procedure. This was evaluated using the International Index of Erectile Function, specifically the Erectile Function domain (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD). The sexual function was not impacted by the treatment with the ProVee System for BPH. No subject experienced sustained retrograde ejaculation or erectile dysfunction after treatment with ProVee System for BPH. | Table 9: Evaluation of Sexual Health (IIEF-5) (ITT Population) | | | | | | | --- | --- | --- | --- | --- | --- | | | Group | Baseline | 3-Months | 6-Months | 12-Months | | Treatment Arm | IIEF-5 n | 149 | 146 | 139 | 132 | | | Mean (SD) | 17.0 (6.5) | 17.5 (6.9) | 17.6 (6.9) | 17.3 (6.6) | | | Change in IIEF-5 | | | | | | | n | N/A | 146 | 139 | 132 | | | Mean (SD) | N/A | 0.5 (5.1) | 0.7 (4.7) | 0.1 (5.4) | | Crossover Arm | IIEF-5 n | 63 | 61 | 61 | 49 | | | Mean (SD) | 17.2 (7.0) | 18.0 (6.9) | 17.6 (7.2) | 17.1 (6.5) | | | Change in IIEF-5 | | | | | | | n | N/A | 61 | 61 | 49 | | | Mean (SD) | N/A | 0.9 (4.0) | 0.4 (5.3) | -0.1 (5.8) | PMA P250011: FDA Summary of Safety and Effectiveness Data 24 of 48 {24} | Table 10: Evaluation of Sexual Health (MSHQ-EjD) (ITT Population) | | | | | | | --- | --- | --- | --- | --- | --- | | | Group | Baseline | 3-Months | 6-Months | 12-Months | | Treatment Arm | MSHQ-EjD: Ejaculatory Function | | | | | | | n | 150 | 146 | 139 | 132 | | | Mean (SD) | 8.9 (3.8) | 10.1 (4.2) | 9.9 (4.3) | 9.8 (3.9) | | | MSHQ-EjD Ejaculatory Bother | | | | | | | n | 150 | 147 | 139 | 132 | | | Mean (SD) | 2.1 (1.6) | 1.4 (1.6) | 1.6 (1.7) | 1.6 (1.5) | | Crossover Arm | MSHQ-EjD: Ejaculatory Function | | | | | | | n | 63 | 61 | 61 | 49 | | | Mean (SD) | 10.0 (4.3) | 10.8 (4.3) | 9.9 (4.3) | 10.0 (4.1) | | | MSHQ-EjD Ejaculatory Bother | | | | | | | n | 63 | 61 | 61 | 49 | | | Mean (SD) | 1.7 (1.7) | 1.5 (1.6) | 1.7 (1.7) | 1.7 (1.6) | Six patients (4%) had the device removed during the 12-month follow up period. There were no reported removal procedure-related adverse events. 2. Effectiveness Results The analysis of effectiveness was based on the 218 evaluable patients (148 ProVee subjects and 70 sham subjects) at the 3-month time point and 150 evaluable patients at the 12-month time point. Key effectiveness outcomes are presented in Tables 11 to 12. Table 11 below shows a mean improvement in IPSS score at 3 months for the treatment arm compared to the sham arm in the ITT population. At 3 months, the mean improvement for the treatment met the 25% super superiority margin over the mean improvement for the sham arm. The actual sham value is -4.5. With a mean improvement in IPSS with 25% super superiority margin, the sham is -5.6. Missing data rates for primary effectiveness endpoints are ≤ 5%; and therefore, PMA P250011: FDA Summary of Safety and Effectiveness Data 25 of 48 {25} the missing data do not need to be imputed in the primary endpoint analysis according to the pre-specified protocol. | Table 11: 3-Months Mean Improvement in IPSS, ProVee versus Sham (ITT Population) | | | | | | --- | --- | --- | --- | --- | | | ProVee Arm (N = 148) | Sham Arm (N = 70) | Difference (95% CI) | p-value | | Mean improvement in IPSS with 25% Super Superiority Margin | -9.5±8.5 | -4.5±7.0 | -5.0 [-7.3, -2.7] | 0.001 | Table 12 shows the 12-month mean improvement in the IPSS score in the ITT population for the ProVee Treatment arm at 12 months over baseline. At 12 months, the treatment arm demonstrated greater than $30\%$ improvement from baseline. | Table 12: 12-Months Mean Percent Improvement in IPSS, ProVee over Baseline (ITT Population) | | | | | | --- | --- | --- | --- | --- | | | ProVee Arm (N = 150) | p-value | ProVee crossover (N = 62) | p-value | | Mean Percent Improvement in IPSS≥30% (SD) | -38.3±33.6 | 0.002 | -33.1 ± 36.0 | 0.002 | | Median | -41.8 | | -33.3 | | | 95% CI | [-43.7, -32.8] | | [-42.3, -24.0] | | PMA P250011: FDA Summary of Safety and Effectiveness Data 26 of 48 {26} Table 13 shows the IPSS responder rates through 12 months in the ITT population. At all the timepoints, the subjects in the treatment arm showed an IPSS improvement of $\geq 30\%$ from baseline. | Table 13: IPSS Responder Rates through 12-Months (ITT Population) | | | | | | --- | --- | --- | --- | --- | | | 1-Month | 3-Months | 6-Months | 12-Months | | ProVee Arm | | | | | | n | 150 | 150 | 150 | 150 | | % of subjects with an IPSS improvement of ≥30% | 57% | 58% | 67% | 61% | | Sham Arm | | | | | | n | 71 | 71 | | | | % of subjects with an IPSS improvement of ≥30% | 41% | 30% | | | | Crossover | | | | | | n% of subjects with an IPSS improvement of ≥30% | 64 56.3% | 64 64.1% | 63 54% | 50 34% | Table 14 shows the QoL improvement in the ProVee Treatment arm through 12-months for the ITT population. The QoL improvements in the treatment arm at PMA P250011: FDA Summary of Safety and Effectiveness Data 27 of 48 {27} each time point was better than the sham arm. Similarly, the QoL improvement in the treatment arm at each time point was better than the baseline. | Table 14: QoL Improvement Over Time (ITT Population) | | | | | | | --- | --- | --- | --- | --- | --- | | Group | Baseline | 1-Month | 3-Months | 6-Months | 12-Months | | ProVee Arm N | 150 | 150 | 148 | 142 | 137 | | Mean (SD) | 4.6 (1.1) | 3.2 (1.6) | 3.1 (1.7) | 2.6 (1.6) | 2.6 (1.7) | | Mean Improvement from Baseline (SD) | | 1.4 (1.7) | 1.5 (1.9) | 2.0 (1.7) | 2.0 (1.7) | | % improvement from Baseline (SD) | | 28.6 (36.1) | 29.8 (41.2) | 41.2 (36.1) | 42.1 (35.6) | | Crossover Arm N | 64 | 64 | 64 | 63 | 50 | | Mean (SD) | 3.7 (1.6) | 2.6 (1.5) | 2.4 (1.3) | 2.5 (1.6) | 2.8 (1.5) | | Mean Improvement from Baseline (SD) | | 1.1 (2.0) | 1.3 (1.8) | 1.1 (1.9) | 1.0 (1.8) | | % improvement from Baseline (SD) | | 8.5 (99.3) | 22.2 (61.9) | 16.9 (83.8) | 13.3 (61.2) | | Sham Arm N | 71 | 70 | 70 | | | | Mean (SD) | 4.5 (1.2) | 3.6 (1.4) | 3.8 (1.6) | | | | Mean Improvement from Baseline (SD) | | 1.0 (1.4) | 0.8 (1.4) | | | | % improvement from Baseline (SD) | | 19.8 (30.4) | 15.4 (33.9) | | | Tables 15a and 15b shows the peak flow rate and post void residual in the ProVee Treatment arm through 12 months for the ITT population. The subjects in the treatment arm had a clinically relevant improvement from the baseline in the uroflowmetry peak flow rate (Qmax) thorough 12-months. The post void residual analysis demonstrated improved voiding in the ProVee Treatment arm compared to baseline. PMA P250011: FDA Summary of Safety and Effectiveness Data 28 of 48 {28} | Table 15a: Peak Flow Rate (Qmax) (ITT Population) | | | | | | | --- | --- | --- | --- | --- | --- | | Group | Baseline | 1-Month | 3-Months | 6-Months | 12-Months | | ProVee Arm N | 150 | 149 | 148 | 137 | 136 | | Mean (SD) | 8.8 (2.0) | 14.7 (6.9) | 14.6 (6.6) | 14.9 (7.0) | 14.2 (6.8) | | Mean Improvement from Baseline (SD) | – | 5.9 (6.9) | 5.8 (6.6) | 6.0 (6.9) | 5.4 (6.7) | | % improvement from Baseline (SD) | – | 77.9 (107.2) | 77.7 (116.9) | 78.9 (103.8) | 71.3 (98.9) | | Crossover Arm N | 64 | 63 | 64 | 63 | 48 | | Mean (SD) | 12.7 (5.6) | 15.9 (7.5) | 15.8 (7.4) | 17.0 (6.9) | 16.0 (7.9) | | Mean Improvement from Baseline (SD) | | 3.2 (7.8) | 3.1 (7.0) | 4.1 (7.1) | 3.0 (7.6) | | % improvement from Baseline (SD) | | 51.4 (141.3) | 47.8 (151.2) | 53.0 (103.7) | 44.8 (129.4) | | Sham Arm N | 71 | 70 | 70 | | | | Mean (SD) | 8.8 (2.2) | 11.6 (5.1) | 12.4 (5.5) | | | | Mean Improvement from Baseline (SD) | – | 2.9 (5.1) | 3.6 (5.1) | | | | % improvement from Baseline (SD) | – | 42.3 (89.3) | 46.6 (68.4) | | | PMA P250011: FDA Summary of Safety and Effectiveness Data 29 of 48 {29} | Table 15b: Post Void Residual Volume (PVR) (ITT Population) | | | | | | | --- | --- | --- | --- | --- | --- | | Group | Baseline | 1-Month | 3-Months | 6-Months | 12-Months | | ProVee Arm N | 150 | 148 | 147 | 137 | 135 | | Mean (SD) | 57.3 (59.4) | 40.9 (52.6) | 44.2 (68.9) | 50.4 (65.1) | 46.1 (57.3) | | Mean Improvement from Baseline (SD) | – | 17.0 (53.4) | 13.9 (68.3) | 8.3 (64.1) | 10.0 (54.1) | | % improvement from Baseline (SD) | – | 22.6 (400.3) | 3.0 (148.5) | 56.8 (464.9) | 7.8 (215.8) | | Crossover Arm N | 64 | 63 | 63 | 63 | 48 | | Mean (SD) | 52.6 (49.3) | 42.9 (57.1) | 39.6 (50.2) | 48.7 (60.7) | 49.1 (61.9) | | Mean Improvement from Baseline (SD) | | 9.8 (54.2) | 13.6 (36.6) | 4.4 (55.6) | 1.8 (48.1) | | % improvement from Baseline (SD) | | 9.7 (114.7) | 37.8 (69.2) | 2.1 (144.4) | 23.1 (160.3) | | Sham Arm N | 71 | 70 | 70 | | | | Mean (SD) | 59.3 (55.4) | 55.6 (72.9) | 57.0 (67.1) | | | | Mean Improvement from Baseline (SD) | – | 4.0 (56.6) | 2.5 (62.4) | | | | % improvement from Baseline (SD) | – | 23.9 (244.8) | 52.1 (215.2) | | | PMA P250011: FDA Summary of Safety and Effectiveness Data 30 of 48 {30} The study also evaluated instances of secondary reintervention using an alternative surgical LUTS therapy and standard pharmacological agents for LUTS therapy. A total of 5 subjects were prescribed pharmacological agents for BPH LUTS therapy for the index procedure through the 12-months. There were no secondary re-interventions using alternative surgical devices. The reinterventions using drugs were adjudicated as device failures in the ITT population. 3. Subgroup Analysis The following baseline characteristics were evaluated for potential association with safety and effectiveness outcomes: age and baseline IPSS. Twenty-eight subjects had a baseline IPSS &lt;20, and 122 subjects had a baseline IPSS ≥ 20. With respect to IPSS change at 3 months, the subgroup of IPSS &lt;20 received less improvement for both treatment arms than the subgroup of IPSS ≥ 20. For the percent IPSS change at 12 months endpoint, the mean percent change for the IPSS &lt;20 subgroup is -29.5%±34.0%, and the mean percent change for the IPSS≥ 20 subgroup is -40.3%±33.3%. Both subgroups experienced improvements on percent IPSS change at 12 months. Regarding subgroup results by age, 80 subjects have a baseline age &lt;65 and 70 subjects have a baseline age ≥ 65. For the IPSS change at 3 months endpoint, the older subgroup received less improvement than the younger subgroup for both treatment arms. For the second the percent IPSS change at 12 months endpoint, the mean percent change for the older subgroup is -32.9%±30.4% and the mean percent change for the younger subgroup is -42.9%±35.6%. Both subgroups experienced improvements on percent IPSS change at 12 months as compared to the performance goal of -30%. 4. Pediatric Extrapolation In this premarket application, existing clinical data was not leveraged to support approval of a pediatric patient population. 3. ProVIDE II Bridging Study The applicant performed a feasibility clinical study to establish reasonable assurance of safety and effectiveness of the ProVee System for BPH in the treatment of obstructive lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) in the US PMA P250011: FDA Summary of Safety and Effectiveness Data 31 of 48 {31} and Ireland under IDE# G230354. Data from this clinical study were the basis for the PMA decision. A summary of the clinical study is presented below. ## A. Study Design Patients were implanted with the ProVee Expander between March 6, 2024, and September 6, 2024. The database for this PMA reflected data collected through March 4, 2025, and included 40 patients. There were 8 investigational sites. The study was a prospective, multi-center, non-randomized bridging study. All subjects were followed up through 60 months. The study did not have a control group. ## 1. Clinical Inclusion and Exclusion Criteria Enrollment in the ProVIDE II Bridging study was limited to the patients who met the following inclusion criteria: 1) Males ≥ 45 years of age 2) IPSS of ≥ 13, IPSS V/S ≥ 1 at baseline assessment 3) Prostate volume of ≥ 30 cc and ≤ 80 cc 4) Prostatic urethral L2 lengths ≥ 3.75 cm by transrectal ultrasound (TRUS) 5) Failed, intolerant, or subject choice to not take a medication regimen for the treatment of lower urinary tract symptoms (LUTS) Patients were not permitted to enroll in the ProVIDE II Bridging study if they met any of the following exclusion criteria: 1) Void volume ≤ 125 ml; Qmax ≥ 12 ml/s; PVR &gt; 250 ml 2) Obstructive median lobe defined by EITHER &gt;10mm protrusion on sagittal mid-prostate plane as measured by TRUS OR an obstructive median lobe seen on cystoscopy e.g., 'ball valve' 3) High bladder neck, with the absence of lateral lobe encroachment indicating a high likelihood of primary bladder neck obstruction 4) Anatomy that would prevent the apices of the ProVee Expander from engaging with the lateral lobes e.g., high degree of bladder neck angulation such that the anterior bladder neck is not visible 5) Acute Urinary retention 6) Known immunosuppression 7) History of or suspected prostate or bladder cancer 8) Baseline prostate specific antigen (PSA) &gt; 10 ng/mL or confirmed or suspected prostate cancer (Subjects with a PSA level above 2.5 ng/mL, or age specific, or local reference ranges should have prostate cancer excluded to the Investigator's satisfaction, including a standard of care (SOC) biopsy if indicated) 9) Recent urinary tract stones OR widespread calcifications on the prostatic urethral wall, within 3 months of index procedure PMA P250011: FDA Summary of Safety and Effectiveness Data 32 of 48 {32} 10) A history of prostatitis within the last two years 11) Active or history of epididymitis within the past 3 months 12) Neurogenic bladder and/or sphincter abnormalities due to Parkinson’s disease, multiple sclerosis, cerebral vascular accident, diabetes 13) History of urinary retention within 12 months of baseline assessment 14) Requiring self-catheterization to void 15) An active urinary tract infection (UTI) at time of index procedure 16) Gross hematuria within 3 months of index procedure 17) Subjects with known allergy to nickel or titanium 18) Life expectancy estimated to be less than 60 months 19) Taking androgens, unless eugonadal state for at least 3 months or greater with a stable dosage for at least 2 months as documented by the Investigator 20) Use of 5-alpha-reductase inhibitors (e.g., dutasteride, finasteride) within 6 months of baseline assessment 21) Use of Phenylephrine / Pseudoephedrine within 24 hours of baseline assessment 22) Use of alpha-blockers (e.g., Terazosin, Doxazosin, Alfuzosin, Tamsulosin) within 2 weeks of baseline assessment 23) Use of estrogen or drug-producing androgen suppression (e.g. gonadotropin-releasing hormonal analogues) within 1 year of baseline assessment 24) Use of antihistamines, anticonvulsants, and antispasmodics within 1 week of baseline assessment unless there is documented evidence that the patient was on the same drug dose for at least 6 months with a stable voiding pattern (the drug dose should not be altered or discontinued for entrance into or throughout the study) 25) Use of anticholinergics or cholinergic medication within 2 weeks of baseline assessment 26) Use of beta-blockers where the dose is not stable. (Stable dose is defined as having the same medication and dose in the last 6 months) 27) Use of Phosphodiesterase-5 Enzyme Inhibitors in doses for BPH within 2 weeks of baseline assessment 28) Current treatment with anticoagulants (e.g., coumadin or enoxaparin) or antiplatelet medications other than aspirin (e.g., clopidogrel, or alternative and ASA). Patient unable to stop taking anticoagulants and/or antiplatelets within 3 days prior to the procedure or coumadin at least 5 days prior to the procedure. Low dose aspirin ≤100mg/day not prohibited 29) Future fertility concerns 30) Previous prostate surgery, balloon dilatation, stent implantation, laser prostatectomy, hyperthermia, or any other invasive treatment to the prostate; including penile implants 31) Previous pelvic irradiation or radical pelvic surgery 32) Previous rectal surgery (other than hemorrhoidectomy) or known history of rectal disease 33) Urethral strictures, bladder neck contracture, or other potentially confounding bladder pathology 34) Urethral pathologies that may prevent insertion of Delivery System PMA P250011: FDA Summary of Safety and Effectiveness Data 33 of 48 {33} 35) Uncontrolled diabetes mellitus including Hgb AIC &gt;8% 36) Overactive bladder (OAB) requiring treatment by OAB medication 37) Urinary incontinence 38) Patients taking tri-cyclic antidepressants 39) Compromised renal function (i.e., serum creatinine &gt;1.8 mg/dl or upper tract disease) 40) Hepatic disorder, bleeding disorders or metabolic impairment that might confound the results of the study or have a risk to subject per investigator's opinion 41) Any major comorbidities or presence of unstable conditions, e.g., uncontrolled HTN, NYHA Class III or IV, cardiac arrhythmias that are not controlled by medication/medical device, myocardial infarction within the past 6 months, COPD with FEV1 &lt;50, renal illness that might prevent study completion or would confound study results 42) Vulnerable populations such as incarcerated or institutionalized adults, inmates, patients with physical, psychological (such as developmentally delayed adults), or medical impairment that might, in the judgment of the Investigator, prevent study completion or comprehension, or may confound study results (including patient questionnaires) 43) History or current medical condition that would result in an unacceptable patient risk if that subject were to be included in the study 44) Any subject that is currently enrolled in another ongoing investigational study 2. Follow-up Schedule All subjects were scheduled to return for follow-up examinations at 1 month and 3 months postoperatively. Preoperatively, the following assessments were completed for during study screening: physical exam and measuring vital signs, International Prostate Symptom Score (IPSS) and Quality of Life (QoL) questionnaires, the abridged International Index of Erectile Function -5 (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Dysfunction (MSHQ-EjD), Face Pain Scale-Revised (FPS-R), Uroflowmetry, Post Void Residual Volume (PVR), Prostate-specific antigen (PSA), Complete blood count (CBC), Renal Function, Transrectal ultrasound (TRUS), cystoscopy and concomitant medications. Postoperatively, the assessments completed included the International Prostate Symptom Score (IPSS) and Quality of Life (QoL) questionnaires, the abridged International Index of Erectile Function -5 (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Dysfunction (MSHQ-EjD), Face Pain Scale-Revised (FPS-R), Uroflowmetry, Post Void Residual Volume (PVR), and concomitant medications. Adverse events and complications were recorded at all visits. PMA P250011: FDA Summary of Safety and Effectiveness Data 34 of 48 {34} The key timepoints are shown below in the tables summarizing safety and effectiveness. ## 3. Clinical Endpoints With regards to safety, the primary safety endpoints included the following: - the rate of device or procedure related serious adverse events were evaluated through 3-months. - the rate of extended post-operative urinary cauterization (&gt;7 days from treatment) for inability to void among patients treated with the ProVee System for BPH. The secondary safety endpoints included the following: - Rate of device or procedure related adverse events at all time points. - Comparison pain at discharge to 1, 3-month follow-up visits per Faces Pain Scale-Revised Questionnaire (FPS-R). - Change in sexual health characterized by change in the International Index of Erectile Function, specifically the Erectile Function domain (IIEF-5) and Male Sexual Health Questionnaire-Ejaculatory Domain (MSHQ-EjD) at 3- month post treatment. - Proportion of subjects with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability evidenced through 3-month follow-up visit. - Assessment of retrieval procedure related adverse events through 3 months related to implant removal. With regards to effectiveness, the primary endpoint would meet if the observed technical success for deploying the expander in the location intended by the user is greater than 95%. The secondary effectiveness endpoints included the following: - Percent of subjects who experience at least a 30% improvement in IPSS from their baseline pre-treatment score at 3- month post treatment. - Percent change in IPSS in the treatment arm compared to baseline at all timepoints post treatment through 3-months. - Mean improvement from baseline in QoL questionnaire at 3-month follow-up visits. - Mean improvement from baseline in uroflowmetry measures of peak flow rate (Qmax) as measured at all timepoints. - Mean improvement from baseline in PVR as measured at all timepoints though 3-months. - Post-procedure incidence of secondary reintervention using alternate surgical LUTS therapy. - Post-procedure incidence of secondary reintervention using prescribed pharmacological agents for BPH LUTS therapy through 3-months. PMA P250011: FDA Summary of Safety and Effectiveness Data 35 of 48 {35} With regard to success/fail criteria, the study was considered a success if the primary effectiveness endpoint was met, and the device had an acceptable safety profile. ## B. Accountability of PMA Cohort At the time of database lock, of 40 patients enrolled in the PMA study, 100% (40) are available for analysis at the completion of the study, the 3-month post-operative visit. Patients were considered enrolled after signing the informed consent form. Eighty-eight subjects were assessed for eligibility for the bridging study. Forty subjects were enrolled in the study. No subject exited the study before the 3-month follow-up. No subjects were lost to follow up. The subject disposition for the non-randomized cohort through 3 months is provided in Figure 5:  Figure 5: Subject Accountability Flow Chart The analysis sets were pre-specified in the protocol as follows: Intent-to-Treat cohort (ITT): All subjects who start the treatment procedure are included in the ITT Cohort. Where there is an attempt to treat, the subject will be considered enrolled in the ITT cohort, regardless of the procedural outcome. Per Protocol Cohort (PP): The Per-Protocol Cohort is defined as the group of subjects who complete the treatment procedure and who complete their 3-month follow-up visit without any protocol violations. PMA P250011: FDA Summary of Safety and Effectiveness Data 36 of 48 {36} Safety Cohort: The safety population is the same as the ITT and Primary Analysis population Cohort for Procedure Success Endpoints: Procedure success related endpoints will be analyzed using the safety/ITT cohort. Cohort for primary and secondary effectiveness endpoints: Analyses for all primary and secondary Effectiveness endpoints will be repeated for the Safety/ITT Cohort, and for the Per-Protocol Cohort. Study Success was based on the Safety/ITT Cohort. Cohort for safety endpoints: Analyses for all safety-related endpoints will be performed using the Safety/ITT Cohort. ## C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a BPH study performed in the US. The demographic information for the subjects is provided in Table 16 and 17. | Table 16: Study Demographics (ITT Population) | | | --- | --- | | Age Mean (SD) | 64.0 (8.7) | | Race | | | American Indian or Alaska Native | 0.0% (0/40) | | Asian | 0.0% (0/40) | | Black or African American | 2.5% (1/40) | | Hawaiian or Pacific Islander | 0.0% (0/40) | | White | 95.0% (38/40) | | Multi-Racial | 0.0% (0/40) | | Other | 2.5% (1/40) | | Not Permitted | 0.0% (0/40) | | Ethnicity | | | Hispanic or Latino | 12.5% (5/40) | | Not Hispanic or Latino | 85.0% (34/40) | | Not permitted | 2.5% (1/40) | | BMI | | | Mean (SD) | 28.3 (3.9) | PMA P250011: FDA Summary of Safety and Effectiveness Data 37 of 48 {37} The baseline prostate characteristics and LUTS severity are provided in the table below: | Table 17: Baseline Prostatic Characteristics and LUTS Severity (ITT Population) | | | --- | --- | | Characteristics | N = 40 Mean (SD) | | Prostatic Volume (mL) | 47.8 (13.6) | | Prostatic Urethral Length (cm) | 4.8 (0.6) | | IPSS Score | 23.5 (5.4) | | IPSS V/S Score | 1.5 (0.3) | | Qmax (mL/sec) | 8.1 (2.4) | | Post Void Residual (mL) | 72.7 (56.8) | | PSA (ng/mL) | 2.9 (2.0) | ## D. Safety and Effectiveness Results ### 1. Safety Results The analysis of safety was based on the ITT cohort of 40 patients available for the 3-month evaluation. The key safety outcomes for this study are presented below in tables 18 to 22. No subjects required extended post-operative urinary catheterization (&gt;7 days post treatment). As reported in Table 18 and Tables 19a and 19b, a total of 30 AEs were reported in 16 subjects (40%). All study AEs were prospectively collected and adjudicated by CEC. There was no SAE through 3-months post index procedure. Of the AEs reported, 1 AEs (in 1 subject) was adjudicated by CEC as device related. 6 AEs (in 4 subjects) were adjudicated by CEC as procedure related. A total of 30 AEs (in 16 subjects) were adjudicated as non-SAEs. The AEs reported were typically mild, transient, and commonly associated with urological procedures. No subjects were classified as Clavien-Dindo Grade IIIb or higher. | Table 18: Adverse Events in the ITT Population | | | | --- | --- | --- | | Event Types | Subjects n (%) | Events n | | Any adverse event | 16 (40.0) | 30 | | Serious adverse events | 0 (0) | 0 | | Non serious adverse events | 16 (40.0) | 30 | PMA P250011: FDA Summary of Safety and Effectiveness Data 38 of 48 {38} | Table 19a: Device Related Adverse Events in the ITT Population | | | | --- | --- | --- | | Adverse Event | ProVee (N=40) | | | | No. Events | No. Subjects (%) | | Hematuria | 1 | 1 (2.5%) | | Total Related AEs | 1 | 1 (2.5%) | | Table 19b: Procedure Related Adverse Events in the ITT Population | | | | --- | --- | --- | | Adverse Event | ProVee (N=40) | | | | No. Events | No. Subjects (%) | | Urinary tract infection | 2 | 2 (5.0%) | | Micturition urgency | 1 | 1 (2.5%) | | Pollakiuria | 1 | 1 (2.5%) | | Hematuria | 1 | 1 (2.5%) | | Nocturia | 1 | 1 (2.5%) | | Total Related AEs | 6 | 4 (10.0%) | As reported in Table 20, the study also evaluated patient pain following index procedure at 1 and 3-months follow-up visits. The pain assessment at the follow up visits had a mean value of 0.4 at 1 month and 0.6 at 3 months (no pain at all/ barely noticeable). | Table 20: FPS-R Pain Score Post Procedure through 3-months (ITT Population) | | | | | --- | --- | --- | --- | | | Discharge | 1-Month | 3-Months | | n | 40 | 40 | 40 | | Mean (SD) | 2.5±2.1 | 0.4 ± 0.8 | 0.6 ± 1.2 | As reported in Table 21 and Table 22, the secondary safety endpoints also included the evaluation of sexual health at 3-months post procedure. This was evaluated using the International Index of Erectile Function, specifically the Erectile Function domain (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD). The sexual function was not impacted by the treatment with the ProVee System for BPH. No subject experienced sustained PMA P250011: FDA Summary of Safety and Effectiveness Data 39 of 48 {39} retrograde ejaculation or erectile dysfunction after treatment with ProVee System for BPH. | Table 21: Evaluation of Sexual Health (IIEF-5) (ITT Population) | | | | --- | --- | --- | | | Baseline | 3-Months | | IIEF-5 | | | | n | 40 | 40 | | Mean (SD) | 16.2 (6.3) | 17.5 (6.3) | | Change in IIEF-5 | | | | n | N/A | 40 | | Mean (SD) | N/A | 1.2 (3.9) | | Table 22: Evaluation of sexual health (MSHQ-EjD) (ITT Population) | | | | --- | --- | --- | | | Baseline | 3-Months | | MSHQ-EjD: Ejaculatory Function | 40 | 40 | | n | | | | Mean (SD) | 8.7 (4.1) | 9.8 (4.1) | | MSHQ-EjD Ejaculatory Bother | | | | n | 40 | 40 | | Mean (SD) | 2.2 (1.6) | 1.5 (1.6) | There were no device removals in the bridging study, and accordingly, no reported removal procedure-related adverse events. 2. Effectiveness Results The analysis of effectiveness was based on the 40 evaluable patients) at the 3-month time point. Key effectiveness outcomes are presented in Tables 23 to 27. Table 23 below shows 100% technical success in the ITT population for the deployment of the expander in the location intended by the user. | Table 23: Primary Efficacy Endpoint – Technical Success (ITT Population) | | | --- | --- | | | Rate | | Technical Success | 100% (40/40) | As shown in Table 24, the mean improvement from baseline in IPSS (total) was 44% and 46% for the 1-month and 3-month follow ups respectively. PMA P250011: FDA Summary of Safety and Effectiveness Data 40 of 48 {40} | Table 24: Symptomatic Improvement Over Time (ITT Population) | | | | | --- | --- | --- | --- | | | Baseline | 1-Month | 3-Months | | IPSS (Total) | | | | | n | 40 | 40 | 40 | | Mean (SD) | 23.5 (5.4) | 12.6 (6.6) | 12.3 (6.0) | | Mean Improvement from Baseline (SD) | | 10.9 (8.3) | 11.2 (7.5) | | % Improvement from Baseline | | 43.8 (36.2) | 45.7 (27.9) | As shown in Table 25, the study also evaluated QoL improvements through 3-months showed greater than 2 points improvement in the quality of life at 1-month and 3-months. | Table 25: Symptomatic improvement over time (QoL) (ITT Population) | | | | | --- | --- | --- | --- | | | Baseline | 1-Month | 3-Months | | QoL | | | | | N | 40 | 40 | 40 | | Mean (SD) | 4.6 (1.0) | 2.4 (1.5) | 2.5 (1.7) | | Mean Improvement from Baseline (SD) | | 2.2 (1.6) | 2.1 (1.6) | | % Improvement from Baseline | | 47.5 (34.4) | 45.4 (36.6) | As shown in Table 26 and 27, functional improvement over time was assessed by Uroflowmetry (Qmax) and Peak Flow rate (PVR) through 3-months. Treatment subjects sustained clinically relevant improvements from baseline in Qmax and PVR. | Table 26: Functional improvement over time (Qmax) (ITT Population) | | | | | --- | --- | --- | --- | | | Baseline | 1-Month | 3-Months | | Qmax (mL/sec) | | | | | N | 40 | 39 | 38 | | Mean (SD) | 8.1 (2.4) | 14.5 (5.3) | 15.3 (6.0) | | Mean Improvement from Baseline (SD) | | 6.3 (4.7) | 7.1 (5.9) | | % improvement from Baseline | | 83.3 (64.5) | 102.5 (100.6) | PMA P250011: FDA Summary of Safety and Effectiveness Data 41 of 48 {41} | Table 27: Functional improvement over time (PVR) (ITT Population) | | | | | --- | --- | --- | --- | | PVR (mL) | 40 | 39 | 37 | | Mean (SD) | 72.7 (56.8) | 43.3 (59.0) | 45.7 (45.5) | | Mean Improvement from Baseline (SD) | | 27.6 (62.3) | 26.6 (61.5) | | % Improvement from Baseline | | 25.6 (117.3) | 53.8 (448.2) | There were no post-procedure incidence of secondary intervention using alternative surgical LUTS therapy or prescribed pharmacological agents for BPH LUTS therapy. ## 3. Subgroup Analyses No subgroup analyses were performed for the ProVIDE II Bridging study results. ## 4. Pediatric Extrapolation In this premarket application, existing clinical data was not leveraged to support approval…