(329 days)
Not Found
No
The device description and performance studies focus on a mechanical implant and its clinical outcomes, with no mention of AI, ML, image processing, or related data analysis techniques.
Yes
The device is intended for the treatment of symptoms due to urinary outflow obstruction secondary to benign prostatic hyperplasia (BPH) and applies radial force to push obstructive tissue away from the urinary path.
No
The device is described as an implantable system for the physical treatment of symptoms due to BPH by pushing obstructive tissue away from the urinary path, rather than for diagnosing a condition.
No
The device description clearly states it consists of a physical implant made of nitinol, a delivery system, and a retrieval kit, all of which are hardware components. There is no mention of any software component.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the treatment of symptoms due to BPH by physically altering the urinary path. This is a therapeutic intervention, not a diagnostic test performed on samples from the body.
- Device Description: The device is an implantable system designed to exert mechanical force on tissue. It does not involve the analysis of biological samples (like blood, urine, or tissue) to diagnose a condition or monitor a patient's health status.
- Lack of IVD Characteristics: The description does not mention any components or processes typical of IVDs, such as reagents, assays, sample collection, or analysis of biomarkers.
- Performance Studies: The performance studies focus on clinical outcomes (IPSS, Qmax, etc.) and adverse events related to the therapeutic effect of the device, not on the accuracy or reliability of a diagnostic test.
In summary, the iTind System is a therapeutic device used to treat a medical condition, not a diagnostic device used to identify or characterize a condition through the analysis of biological samples.
N/A
Intended Use / Indications for Use
The iTind System is intended for the treatment of symptoms due to urinary outflow obstruction secondary to benign prostatic hyperplasia (BPH) in men age 50 and above.
Product codes (comma separated list FDA assigned to the subject device)
QKA
Device Description
The iTind System consists of the iTind implant, delivery system, and retrieval kit. The iTind implant is made of nitinol and pre-mounted on a dedicated guide wire. In its folded configuration, the implant is inserted through a cystoscope sheath and deployed within the bladder neck and prostatic urethra where it assumes its expanded configuration (maximum diameter 33mm; length 50mm). When expanded, the struts of the implant exert radial force on the bladder neck and prostatic urethra, pushing obstructive tissue away from the urinary path. The implant is designed to cover the entire length of the prostatic urethra, from the bladder neck to a point proximal to the external urinary sphincter. It is left in position for 5-7 days and subsequently removed using a Foley catheter. The deployment and removal of the implant are described in the Instructions for Use supplied by Medi-Tate. The device is compatible with commercial cystoscopes at least 20Fr in diameter. To remove the iTind implant, the retrieval kit (snare) is used. The snare is inserted through a Foley catheter and the retrieval suture is tied to the loop of the snare (with the attached suture) is then pulled completely out of the Foley catheter. With the retrieval suture held taut, the Foley catheter is inserted into the meatus and guided through the urethra until it meets the iTind implant. The retrieval suture is then pulled firmly to retract the implant into the Foley catheter. The Foley catheter, along with the enclosed implant, are then removed from the urethra.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
bladder neck and prostatic urethra
Indicated Patient Age Range
men age 50 and above
Intended User / Care Setting
Should only be used by clinicians trained in endo-urological procedures and the management of their complications.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The De Novo request presents the outcomes of three prospective studies, including one controlled, pivotal study, which have a total of (0)(4) enrolled subjects, with > (0) (0) iTind-treated subjects who have undergone follow-up evaluation out to at least 12 months.
MT-01 Study:
- Study Type: One-arm, multi-center, two-step, international feasibility and prospective study.
- Sample Size: 32 iTind subjects (31 completing 12-month FU). 31 subjects completed follow-up to 36 months.
- Key Results:
- Increase in maximal urinary peak flow of 4.1, 4.1 and 4.9 ml/s at the 3, 6 and 12-month time-points.
- Statistically significant increase in peak urinary flow rate (Qmax) from baseline, and reduction in International Prostate Symptom Score (IPSS) and Quality of Life (QoL) scores over 36 months.
- At 12 months, 25/32 subjects reported an IPSS improvement of at least 5 points.
- Four (4) expected early-onset complications reported: urinary retention, transient incontinence, prostatic abscess, and urinary tract infection, all resolved within 30 days without sequelae. No further complications recorded in follow-up.
MT-02 Study:
- Study Type: International, prospective, single-arm, multi-center, safety and efficacy study.
- Sample Size: 81 iTind subjects (67 completing 12-month FU).
- Key Results:
- At 6-month follow-up, 85.3% of treated patients (N=70) reported a > 3-point improvement in IPSS.
- At 12-month follow-up, 88.9% of treated patients (n=67) reported a > 3-point improvement in IPSS.
- Patients reported enhanced quality of life, and an increase in mean Qmax, from 7.6 ml/s at baseline to 12 ml/s at 12 months.
- Three (3.7%) patients experienced serious adverse events resolved within 10 days. Majority of complications were low-grade, self-limiting, mostly hematuria and expected lower urinary tract symptoms, with 43.2% of all patients experiencing some AE.
- None of the sexually active patients reported any erectile or ejaculatory dysfunction.
MT-03 Study (Pivotal Study):
- Study Type: Randomized, controlled, efficacy-assessor-blinded, multi-center, international prospective study.
- Sample Size: 118 iTind (81 completing 12-month FU), 57 Sham (NA). Total 185 subjects randomized (128 iTind group, 57 Sham).
- Effectiveness Results:
- First co-primary endpoint (IPSS score difference at 3 months): iTind group showed improvement of approximately 10 points from baseline, but did not achieve statistical significance compared to Sham group (P-Value 0.104). 79% of iTind patients were responders (> 3-point reduction) vs. 60% in sham group.
- Second co-primary endpoint (IPSS score change at 12 months for iTind): Significant improvement in IPSS scores (Change from Baseline -8.7, P 3-point improvement in IPSS at 6 months.
- 88.9% of treated patients (n=67) reported a > 3-point improvement in IPSS at 12 months.
- Mean Qmax increase: from 7.6 ml/s at baseline to 12 ml/s at 12 months.
MT-03 Study:
-
Effectiveness:
- IPSS Score (Baseline to 3 months, iTind): Change from Baseline -10.6.
- IPSS Score (Baseline to 3 months, Sham): Change from Baseline -8.3.
- IPSS Score (Sham - iTind, 3 months): Difference 2.5 (95% Lower Limit -0.5, 95% Upper Limit 5.6), P-Value 0.104.
- IPSS Score (Baseline to 12 months, iTind): Change from Baseline -8.7 (95% Lower Limit -10.6, 95% Upper Limit -6.9), P-Value 3-point reduction in IPSS at 3 months):** 79% in iTind group, 60% in sham group.
- Peak Flow Rate (PFR) Change from Baseline (at 3 months): iTind 4.4 ml/sec, Sham (b) (4) (Table is cut off).
- Post-Void Residual Urine Volume Change from Baseline (at 3 months): iTind -5.0 ml.
- International Index of Erectile Function (IIEF) Score Change from Baseline (at 3 months): iTind 4.0.
- Sexual Health Inventory for Men (SHIM) Score Change from Baseline (at 3 months): iTind 0.4.
-
Safety (MT-03):
- Dysuria: iTind 22.9% subjects, Sham 8.8% subjects.
- Hematuria: iTind 13.6% subjects.
- Pollakiuria: iTind 6.8% subjects, Sham 1.8% subjects.
- Urinary retention: iTind 5.9% subjects.
- Micturition urgency: iTind 5.1% subjects, Sham 1.8% subjects.
- All AEs: iTind 38.1% subjects, UroLift 87.1% subjects.
- Related AEs: iTind 32.2% subjects, UroLift 80.7% subjects.
- Serious AEs: iTind 8.5% subjects, UroLift 11.4% subjects.
- Related SAEs: iTind 2.5% subjects, UroLift 1.4% subjects.
- Mean implantation duration: 4.2 minutes.
- Mean VAS pain score: 4.2.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
The iTind System was classified through the De Novo pathway (DEN190020), not the 510(k) pathway. Therefore, no predicate devices were used to claim substantial equivalence.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 876.5510 Temporarily-placed urethral opening system for symptoms of benign prostatic hyperplasia.
(a)
Identification. A temporarily-placed urethral opening system for symptoms of benign prostatic hyperplasia (BPH) is a prescription use device that is inserted transurethrally and deployed at the prostate. The implant is designed to increase prostatic urethral patency by increasing prostatic opening. It is intended for the treatment of symptoms due to urinary outflow obstruction secondary to BPH in men.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing with the device under anticipated conditions of use must evaluate improvement in urinary outflow symptoms and document the adverse event profile.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) Performance data must demonstrate the sterility of the patient-contacting components of the device.
(4) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
(5) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Deployment and removal; and
(ii) Mechanical strength.
(6) Labeling must include:
(i) Instructions for use, including the recommended training for safe use of the device;
(ii) A summary of the clinical performance testing conducted with the device, including device- and procedure-related adverse events; and
(iii) A shelf life.
0
DE NOVO CLASSIFICATION REQUEST FOR ITIND SYSTEM
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Temporarily-placed urethral opening system for symptoms of benign prostatic hyperplasia. A temporarily-placed urethral opening system for symptoms of benign prostatic hyperplasia (BPH) is a prescription use device that is inserted transurethrally and deployed at the prostate. The implant is designed to increase prostatic urethral patency by increasing prostatic opening. It is intended for the treatment of symptoms due to urinary outflow obstruction secondary to BPH in men.
NEW REGULATION NUMBER: 21 CFR 876.5510
CLASSIFICATION: Class II
PRODUCT CODE: QKA
BACKGROUND
DEVICE NAME: iTind System
SUBMISSION NUMBER: DEN190020
DATE OF DE NOVO: April 20, 2019
- Medi-Tate Ltd. CONTACT: 14 Hailan St. Or Akiva, ISRAEL 3060000
INDICATIONS FOR USE
The iTind System is intended for the treatment of symptoms due to urinary outflow obstruction secondary to benign prostatic hyperplasia (BPH) in men age 50 and above.
LIMITATIONS
- The iTind System is restricted to use by prescription only.
- The iTind System should only be used by clinicians trained in endo-urological ● procedures and the management of their complications.
- The iTind system is for single use. Do not re-sterilize or reuse any part of the svstem.
- . The iTind System is contraindicated in patients with:
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- ା active urinary tract infection or prostatitis:
- artificial urinary sphincter or any implant (metallic or nonmetallic) within the urethra:
- any patient condition which, to the implanting physician's opinion, may cause i complications during the deployment of the device;
- A thorough clinical evaluation should be performed on all patients presenting for . treatment for BPH such as recommended by the American Urological Association (AUA) Guidelines for Surgical Management of BPH.
- The risks of implanting the iTind System in patients with blood coagulation . disorders, compromised immune systems, or any other conditions that would compromise healing should be carefully considered against the possible benefits.
- Do not use the iTIND System if the patient has a known allergy to nickel. .
- . Potential complications from the cystoscopy procedure, and/or the presence of the iTind device in the prostatic urethra or the deployment/retrieval procedure, include:
- 手 Fever
- -Blood in urine (hematuria)
- -Pain
- ା Urinary tract infection (UTI)
PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The iTind System consists of the iTind implant, delivery system, and retrieval kit. The components are described below.
Figure 1. iTind implant and delivery system.
Figure 2. iTind retrieval kit (snare).
Image /page/1/Figure/16 description: This image shows a diagram of a tool with several labeled parts. Part 2 is a loop, and part 3 is a connector attaching the loop to a rod labeled as part 1. Part 5 is a cylindrical component with a handle labeled as part 6, and part 7 is another rod-shaped component.
| Component | |
|---|---|
| iTind implant (Item 1, 2, 3, 4) | |
| Introducer Sheath (Item 5 and 6) | |
| Guide Wire (Item 7) |
Image /page/1/Figure/18 description: In the image, a hand is holding a small, flat object labeled as '1'. Next to the hand, there is a cylindrical object labeled as '2'. The hand appears to be inserting the flat object into the cylindrical object. The image is a simple diagram with clear labels.
| Component | |
|---|---|
| Snare (Item 1) | |
| Sheath (Item 2) |
iTind implant
The iTind implant is made of nitinol and pre-mounted on a dedicated guide wire. In its folded configuration (Figure 3, left figure), the implant is inserted through a cystoscope sheath and deployed within the bladder neck and prostatic urethra where it assumes its expanded
2
configuration (Figure 3, center & right figures) (maximum diameter 33mm; length 50mm). When expanded, the struts of the implant exert radial force on the bladder neck and prostatic urethra, pushing obstructive tissue away from the urinary path. The implant is designed to cover the entire length of the prostatic urethra, from the bladder neck to a point proximal to the external urinary sphincter. It is left in position for 5-7 days and subsequently removed using a Foley catheter. The deployment and removal of the implant are described in the Instructions for Use supplied by Medi-Tate. The device is compatible with commercial cystoscopes at least 20Fr in diameter.
Figure 3. The iTind implant: retracted (left), expanded (middle), and expanded-closeup (right).
Image /page/2/Picture/2 description: The image shows a medical device in three different stages of deployment. The device appears to be a basket-like structure made of thin, flexible wires, attached to a long, slender tube. In the first image, the basket is collapsed and contained within a clear sheath, while in the second and third images, the basket is gradually expanding, revealing its open, cage-like form. The device is likely used for capturing or retrieving objects within the body during medical procedures.
Placement
The iTind implant is advanced into the bladder using a delivery system through a standard cystoscope. The iTind implant, with its suture attached to it, is preloaded on the delivery system. The cystoscope is inserted through the urethra until reaching the bladder as in routine cystoscopy procedures. At this stage, the optic fiber is withdrawn and the loaded delivery system is inserted through the cystoscope sheath. The delivery system is completely withdrawn, leaving the iTind implant connected to the guide wire only by means of the suture. At this stage, regular cystoscope optics are used over the guide wire for final positioning of the iTind implant at the prostatic urethra under visualization. As soon as the iTind implant is positioned, the knot at the end of the thread protruding from the guide wire is cut, and the guide wire is withdrawn as well.
Retrieval
To remove the iTind implant, the retrieval kit (snare) is used. The snare is inserted through a Folev catheter and the retrieval suture is tied to the loop of the snare (with the attached suture) is then pulled completely out of the Foley catheter. With the retrieval suture held taut, the Foley catheter is inserted into the meatus and guided through the urethra until it meets the iTind implant. The retrieval suture is then pulled firmly to retract the implant into the Foley catheter. The Foley catheter, along with the enclosed implant, are then removed from the urethra.
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SUMMARY OF NONCLINICAL/BENCH STUDIES
BIOCOMPATIBILITY/MATERIALS
The iTind System is a surface contacting device in contact with the mucosal membrane for a prolonged duration. Therefore, cytotoxicity, sensitization, intracutaneous reactivity, implantation, and material-mediated pyrogenicity were performed on the iTind implant, delivery system and retrieval kit in accordance with the FDA Guidance "Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" (June 16, 2016). In addition, sub-acute systemic toxicity testing (4-week study in rats) and genotoxicity testing (mouse lymphoma assay only) were conducted, and genotoxicity/sub-acute systemic toxicity was also assessed via analytical chemical characterization followed by toxicological risk assessment. Biocompatibility testing was conducted under GLP conditions on the final, finished iTind System device, as shown in Table 1. All tests were passed, indicating that the device materials are biocompatible and appropriate for the indication for use. The results support the biocompatibility of the iTind System.
| Biological Effect | Test | Standard | Result |
|---|---|---|---|
| Cytotoxicity | MEM elution | ISO 10993-5 | Passed |
| Sensitization | Guinea pig maximization | ||
| sensitization | ISO 10993-10 | Passed | |
| Intracutaneous | |||
| Reactivity | Intracutaneous toxicity study in | ||
| rabbits | ISO 10993-10 | Passed | |
| Implantation | Muscle implantation study in | ||
| rabbits | ISO 10993-6 | Passed | |
| Material-mediated | |||
| Pyrogenicity | Rabbit pyrogen test | USP 34 | Passed |
| Sub-acute systemic | |||
| toxicity | 4-week repeat dose IV and IP | ||
| study in rats | ISO 10993-11 | Passed | |
| Genotoxicity | Mouse lymphoma assay | ISO 10993-3 | Passed |
| Genotoxicity/Sub- | |||
| acute systemic | |||
| toxicity | Analytical chemical | ||
| characterization followed by | |||
| toxicological risk assessment | ISO 10993-18 | ||
| ISO 10993-17 | Passed |
Table 1. Biocompatibility testing performed on the iTind System
STERILITY
The iTind implant/delivery system and retrieval kit are supplied as a single-use. disposable, sterile procedure kit. The iTind implant and delivery system are packaged together, and the retrieval kit is packaged separately. The system components are sterilized using Ethylene Oxide (EO) gas sterilization. EO sterilization validation was
4
conducted in conformance with ISO 11135:2014 and demonstrated a Sterility Assurance Level (SAL) of 106 Further, the device was tested for EO residuals in conformance with ISO 10993-7 to ensure that the maximum residual levels of EO and ethylene chlorohydrin (ECH) remaining on the product after sterilization do not exceed the recommended limits for medical devices in prolonged exposure with the patient.
SHIPPING DISTRIBUTION, SHELF LIFE AND PACKAGING INTEGRITY
The iTind implant/delivery system and retrieval kit packaging configurations consist of a single barrier Tyvek® pouch. The iTind implant/delivery system is pouched and placed into a cardboard box. Ten (10) labeled retrieval kits pouches (i.e., snares) are packaged in a cardboard box. Each box includes an Instructions for Use ("IFU") pamphlet. Packaging validation testing was completed on lot controlled, finished, aged, finished product that met all dimensional and visual requirements.
Simulated shipping distribution was conducted on iTind System components after EO sterilization and environmental conditioning in conformance with ASTM D4332 and ASTM D4169, respectively. Post-simulated shipping distribution and environmental conditioning, packaging integrity was tested via visual inspection and packaging integrity tests. Specifically, samples were tested via dye penetration test per ASTM F1929 and seal strength test per ASTM 88/F88M. All tests met the predetermined acceptance criteria.
A shelf life of two (2) years was established for the iTind System through accelerated and real-time aging studies of EO-sterilized test articles. Accelerated aging was conducted in conformance with ASTM F1980. Post-aging, packaging integrity was tested via visual inspection and packaging integrity tests. Specifically, samples were tested via dye penetration test per ASTM F1929, seal strength test per ASTM 88/F88M, and burst test per ASTM F1140/F1140. All tests met the predetermined acceptance criteria.
In addition, visual and functional testing also assessed the tensile force at break, device dimensions, crimpability, radial force, force required to insert the device through a cvstoscope, and deployment tests. All tests met their predetermined acceptance criteria. The results support the sterility of the iTind System and demonstrate that the packaging materials can withstand the rigors of shipping and distribution maintaining the integrity of the sterile barrier and the device will perform as intended through the indicated shelf life.
MAGNETIC RESONANCE (MR) COMPATIBILITY
Non-clinical testing and MRI simulations were performed to evaluate the iTind implant. Testing was performed on the device in two configurations: 1) fully expanded for displacement, torque, and artifact testing, and 2) compressed (17 mm diameter) for RF heating testing. RF simulations showed that at both 1.5 and 3.0 Tesla, the maximum heating occurred in the compressed configuration. The heating extents predicted by the simulations were then confirmed by bench testing showing similar levels of heating in 1.5 and 3.0 Tesla MR systems. The testing demonstrated that the iTind implant is MR
5
Conditional. A patient with an implant can be scanned safely in an MR system under the following conditions:
- . Static magnetic field of 1.5 Tesla or 3 Tesla, only;
- . Maximum spatial gradient magnetic field of 4.000 gauss/cm (40 T/m):
- Maximum MR system reported. whole body averaged specific absorption rate . (SAR) of 2 W/kg for 15 minutes of scanning (i.e., per pulse sequence) in the Normal Operating Mode.
Under the scan conditions defined, an implant from the iTind Device is expected to produce a maximum temperature rise of 3.7℃ after 15 minutes of continuous scanning (i.e., per pulse sequence). In non-clinical testing, the image artifact caused by the iTind implant extends only approximately 5 mm from the device when imaged with a gradient echo pulse sequence and a 3 Tesla MR system. The results support that the iTind System can be labeled as MR Conditional.
PERFORMANCE TESTING - BENCH
The preclinical testing demonstrates that the device performs as intended per the device specifications. Further, the preclinical tests described below are consistent with the principles of the FDA guidance, "Guidance for the Non-Clinical and Clinical Investigation of Devices Used for the Treatment of Benign Prostatic Hyperplasia (BPH)," August 17, 2010 ("FDA's Guidance").
Functional Performance (Bench) Testing of iTind System
Functional performance testing demonstrated that the iTind implant (and delivery system) and retrieval kit consistently met its acceptance criteria according to FDA recognized standards and pre-defined acceptance criteria. All tests were conducted on samples that were EO sterilized and exposed to shipping and distribution conditions, at baseline followed by 2 years of accelerated aging before testing the device. Each of the functional bench tests is summarized below.
Crimping
The iTind implant is crimped into a delivery system prior to implantation. This test is meant to ensure that the crimping and releasing of the iTind implant does not cause any damage to the device components and that the device resumes its design and expanded dimensions following crimping and release. The testing was completed to do the following:
- To demonstrate that the iTind implant can withstand crimping, loading into । the delivery system and expansion, and that the iTind implant will change less than 2mm in its dimensions following multiple crimping cycles.
- To demonstrate the symmetry and uniformity of the device after expansion. ।
- । To demonstrate that the device does not experience any defects during crimping, loading, and expansion.
The crimping testing was done on 30 systems, in order to meet 90% reliability and 95% confidences in accordance with ISO 2859-1 Second Edition 1999-11-15.
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Sampling Procedures For Inspection Bv Attributes - Part 1, which are designed to test functionality of final assembled implants. The testing was performed using a tensile test (b) (4) and a (b) (4) Radial Expansion Force Gauge. Crimping the iTind implant through the PTFE Delivery Tube: Not more than (b) (4)after 10% over the acceptance limit defined, the test could be stopped. The acceptance criterion is (4) (4) as this is the greatest force exerted on the device during insertion. All test samples met the acceptance criterion.
Radial Force
The purpose of this test is to challenge the iTind implant by crimping and measuring the radial force at different diameters. The results are used to evaluate the pressure of the device on the tissue. The radial force test was conducted on 30 systems, in order to meet 90% reliability and 95% confidences, according to ISO 2859-1 Second Edition 1999-11-15, Sampling Procedures For Inspection By Attributes - Part 1, which is designed to test functionality of final assembled implant. The testing was performed using a (b) (4) Radial Expansion Force Gauge. The acceptance criterion was "> 1.0 N in crimping diameter of 5 mm to 11 mm, after "cycles of crimping and expanding." The acceptance criterion is based on the amount of force required to imprint itself into the tissue. This was derived from systolic blood pressure, peripheral pressure and device area. Based on this calculation, the iTind implant should apply more than 0.5 N in order to imprint itself into the tissue. Therefore, the acceptance criterion was set to 1.0 N. All test samples met the acceptance criterion.
Tensile Force at Break
The iTind implant and delivery system is a collection of machined and extruded parts that are connected by various means; the system must perform the mechanical action needed for the implantation procedure, without any failure of either the bonds between the various parts of the system, or of the moving parts within the system in accordance to specifications. The tensile FAB test was conducted on 30 systems, in order to meet 90% reliability and 95% confidences according to ISO 2859-1 Second Edition 1999-11-15, Sampling Procedures For Inspection By Attributes - Part 1, which are designed to test every bond or connection within the iTind implant. The test was performed using a tensile test (b) (4) The devices were arranged in accordance with the test figures. Each device is connected to the machine to conduct tensile testing. After (b) (4) over the acceptance limit defined (b) (4) the test should be stopped. The acceptance criterion was selected to be(b) (4) because it is 2.5 times the forces encountered during device insertion and retrieval. All test samples met the acceptance criterion.
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Deployment
iTind implant was deployed through a silicone anatomical model of the bladder neck, which mimics the resistance in the urethra. The tested iTind implants were visually checked for correct deployment, removal and correct positioning. The Deployment test was conducted on 30 systems, in order to meet 90% reliability and 95% confidence, according to ISO 2859-1 Second Edition 1999-11-15, Sampling Procedures For Inspection By Attributes - Part 1, which are designed to test functionality of final assembled implant. iTind implant was deployed through a silicone anatomical model of the bladder neck, which mimics the resistance in the urethra. The criterion is based on visual inspection. Sample must be compared to the gold standard picture of full setup with close views of important parts. All test samples met the acceptance criterion.
iTind Implant Dimensions
The purpose of this test is to ensure the device dimensions comply with the predefined acceptance criterion. The dimension testing was completed on 30 systems, in order to meet 90% reliability and 95% confidence, according to ISO 2859-1 Second Edition 1999-11-15, Sampling Procedures For Inspection By Attributes - Part 1, which are designed to test functionality of final assembled implant. All dimensions of the device were measured using a caliper and confirmed to be consistent with the technical drawings. All devices were tested prior to crimping and after "cycles of crimping and expanding. The difference in dimensions before and after crimping should be less than 2mm. The acceptance criteria of 2mm was deemed appropriate to allow for proper deployment given the size of the bladder neck. All test samples met the acceptance criterion. For all 30 units, the difference between each set of the before and after measurements was less than 0.3mm.
Corrosion Testing
The corrosion resistance test was intended to establish that the iTind System shows no sign of corrosion. The sample size consisted of ® "final device configurations (i.e., the iTind System). Test Methods: Real-time immersion testing with open circuit potential monitoring: Immersion in urine or a urine substitute at (b) (4)under aerated conditions; day duration, as this is a worstcase assessme s compared to a 7 day implantation time; Monitoring the open circuit voltage, visual assessment, comparing the appearance of the surface before and after the test, and SEM assessment to examine for presence of pitting or other corrosion. Study success was defined as no visual evidence of corrosion and no sudden changes in open circuit voltages. There shall be no signs of corrosion on the blade of the test specimen. All samples met the predetermined acceptance criterion.
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SUMMARY OF CLINICAL INFORMATION
The De Novo request presents the outcomes of three prospective studies (as shown in Table 2, below), including one controlled, pivotal study, which have a total of (0)(4)enrolled subjects, with > (0) (0) iTind-treated subjects who have undergone follow-up evaluation out to at least 12 months.
| Table 2. Studies with Prospective Data |
|---|
| Study |
| Study | Subjects Enrolled
(completed 12-month FU) |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|
| MT-01 (OUS) - One-arm, multi-center, two-steps international feasibility
and prospective study to assess the safety and efficacy of Medi-Tate
Temporary Implantable Nitinol Device (TIND) in subjects presenting
Bladder Outlet Obstruction secondary to BPH. | 32 iTind (31) |
| MT-02 (OUS) - One-arm, multi-center, international prospective study to
assess the efficacy of Medi-Tate Temporary Implantable Nitinol Device
(TINDTM) in subjects with Benign Prostatic Hypertrophy (BPH). | 81 iTind (67) |
| MT-03 (US/OUS) - A pivotal study, randomized, controlled, efficacy-
assessor-blinded, multi-center, international prospective study to assess
the safety and effectiveness of Medi-Tate i-Temporary Implantable
Nitinol Device (iTind) in subjects with symptomatic Benign Prostatic
Hyperplasia (BPH). | 118 iTind (81)
57 Sham (NA) |
MT-01 Study
MT-01 was a one-arm, multi-center, two-step, international feasibility and prospective study to assess the safety and efficacy of Medi-Tate Temporary Implantable Nitinol Device (TIND) in subjects presenting Bladder Outlet Obstruction secondary to BPH. The studyincluded 31 subjects completing follow-up to 36 months. This study was conducted outside the United States and was designed as a single-arm, feasibility study. The objective of the study was to assess the safety and efficacy of the TIND System in male subjects age 50 and older with bladder outlet obstruction (BOO) secondary to BPH. The primary efficacy endpoint was to increase maximal urinary peak flow by at least 5 ml/s in at least 75% of patients at 3, 6 and 12 months. The primary safety objective was the incidence of unexpected serious adverse events related to the TIND implant and the implantation/retrieval procedures. Increases in maximal urinary peak flow of 4.1, 4.1 and 4.9 ml/s were attained at the 3, 6 and 12-month time-points. There was a statistically significant increase in peak urinary flow rate (Omax) from baseline, and reduction in International Prostate Symptom Score (IPSS*) and Quality of Life (QoL **) scores over 36 months. At 12 months, 25/32 subjects reported an IPSS improvement of at least 5 points. Four (4) expected early-onset complications were reported, including urinary retention, transient incontinence, prostatic abscess and urinary tract infection. These were managed via catheter placement, early removal of device, readmission/antibiotics, and oral antibiotics, respectively. All resolved within 30 days without sequelae. No further complications were recorded during the follow-up period.
- Total IPSS score is based on the sum of patient responses to items 1 to 8 of the IPSS questionnaire (for lower urinary symptoms; scored 0-5 for each item, for a total score ranging from 0 to 40).
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** IPSS QoL Score, which corresponds to item 8 of the IPSS questionnaire, separately.
MT-02 Study
MT-02 was an international, prospective, single-arm, multi-center, safety and efficacy study on the iTind device used to treat Benign Prostatic Hyperplasia (BPH). A total of 81 subjects were enrolled in this study. The primary efficacy and safety endpoints were a ≥ 3-point IPSS score reduction in at least 75% of the subjects at 6 months follow-up and the incidence of unexpected serious adverse events related to the device and/or implantation/retrieval procedures, respectively. At the 6-month follow-up visit. 85.3% of treated patients (N=70) reported a > 3point improvement in IPSS. At the 12-month follow-up visit, 88.9% of treated patients (n=67) reported a > 3-point improvement in IPSS. Further, patients reported enhanced quality of life, and an increase in mean Qmax, from 7.6 ml/s at baseline to 12 ml/s at 12 months.
Three (3.7%) patients experienced serious adverse events that were subsequently resolved within 10 days. The vast majority of complications were low-grade, self-limiting, and consisted mostly of hematuria and expected lower urinary tract symptoms, with 43.2% of all patients experiencing some AE (18.5% related; 22.2% device- and/or procedure-related; 14.8% procedure related). None of the sexually active patients reported any erectile or ejaculatory dysfunction.
MT-03 Studv
The MT-03 pivotal study was an FDA-approved Investigational Device Exemption (IDE) Study. The study is a randomized, controlled, efficacy-assessor-blinded, multi-center, international prospective study to assess the safety and effectiveness of Medi-Tate i-Temporary Implantable Nitinol Device (iTind) in subjects with symptomatic Benign Prostatic Hyperplasia (BPH).
A total of 185 subjects were randomized (128 in the iTind group and 57 in Sham) and included in the Intent-to-Treat (ITT) population. A total of 175 patients underwent iTind implantation/Sham treatment, including 118 in the iTind group and 57 in the Sham group. The sham procedure consisted of insertion and removal of a Foley catheter. Of the ten patients that were assigned to the iTind arm but did not undergo implantation, nine were screen failures that were randomized by mistake and one was excluded intraoperatively due to a stricture.
Results – Effectiveness
The first co-primary endpoint, which was the difference in IPSS score between iTind and Sham groups at 3 months (Table 3, below), showed an improvement of approximately 10 points from baseline for the iTind group, which did not achieve statistical significance when compared with the Sham group under the pre-specified statistical model. In addition, 79% of iTind patients were responders (those who showed a > 3-point reduction), compared to 60% in the sham group.
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| Treatment
Group | N
(baseline) | N
(3 months) | IPSS
(Baseline) | IPSS
(3 months) | IPSS
(Change from
Baseline) | 95%
Lower
Limit | 95%
Upper
Limit | P-Value |
|--------------------|-----------------|-----------------|--------------------|--------------------|-----------------------------------|-----------------------|-----------------------|---------|
| iTind | 127 | 84 | 26.7 | 15.7 | -10.6 | -11.8 | -8.1 | NA |
| Sham | 57 | 40 | 27.7 | 19.2 | -8.3 | -10.1 | -4.8 | NA |
| Sham - iTind | NA | NA | 1.0 | 3.5 | 2.5 | -0.5 | 5.6 | 0.104 |
Table 3. Changes in IPSS Score at 3 Months *
*SAP Mixed Model; Intend-to-Treat (ITT) Population
The second co-primary endpoint of the study, which was the change in IPSS Score at 12 months compared to the baseline for the iTind group (Table 4, below), showed a significant improvement of IPSS scores. The sham group could not be compared at 12 months because their follow up was limited to 3 months to enable them to resume active treatment.
Table 4. Changes in IPSS Score at 12 Months*
| Treatment
Group | N
(12 months) | Visit | Change from Baseline
(at 12 months) | 95% Lower
Limit | 95% Upper
Limit | P-Value |
|--------------------|------------------|-----------|----------------------------------------|--------------------|--------------------|---------|
| iTind | 81 | 12 Months | -8.7 | -10.6 | -6.9 | 50 |
| IPSS | | ≥ 10 | | ≥ 13 |
| Prostate (cc) | | 25-75 | | ≤ 80 |
| Comparison of Other Miscellaneous Study Parameters | | | | |
| Sham (Insertion) | NA | Foley (In & Out) | NA | Cystoscopy +audio |
| Sham (Retrieval) | NA | Foley (In & Out) | NA | NA |
| Sites | 14 US (2 OUS) | - | 14 US (5 OUS) | - |
| In-study meds* | 13 | 7 | | |
- During the iTIND study, the investigator had the discretion to treat patients with alternative BPH treatment methods (medications, surgeries, or other devices) when necessary. The alternative treatments included alpha blockers (Rapaflo, Uroxatrol, Tamsulosin, Flomax, Labetalol, Carvedilol), surgery (TURP, UroLift), Antimuscarinics (Ditropan, Aclidinium Bromure, Solifenacine). All efficacy measurements from the day of alternative treatment onwards were considered "missing" and imputed as baseline values (resulting in treatment failures with no change from baseline).
Results - Effectiveness
Image /page/14/Figure/3 description: The image is a title for a figure. The title states, "Figure 4. Comparing IPSS scores between iTind (MT-03) and UroLift (L.I.F.T.) studies."
Image /page/14/Figure/4 description: This image is a bar graph comparing the 3-month change and 12-month change of MT-03 and L.I.F.T. (for UroLift). The y-axis ranges from 0 to -20, with both MT-03 and L.I.F.T. showing negative changes at 3 months and 12 months. The error bars indicate the variability in the data for each group.
** Roehrborn et al. 2013; Error bar: Standard Deviation (SD)
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Image /page/15/Figure/0 description: This image is a bar graph comparing the change at 3 months and 12 months for MT-03 and L.I.F.T. (for UroLift). The y-axis ranges from 0 to -5. At 3 months, MT-03 is around -1.75 and L.I.F.T. is around -0.5. At 12 months, MT-03 is around -1.5 and L.I.F.T. is around -2.5.
Image /page/15/Figure/1 description: The image is a title for a figure. The title reads "Figure 5. Comparing QoL scores between iTind (MT-03) and UroLift (L.I.F.T) studies". The title indicates that the figure will compare the quality of life scores between two different studies, iTind and UroLift. The studies are abbreviated as MT-03 and L.I.F.T, respectively.
While the iTind results in the MT-03 pivotal study were not significantly different compared to the sham (Table 5), the observed IPSS and QoL improvements were similar to the UroLift study at 3 months, as summarized in Figures 4 and 5. Thus, the data further support the clinical benefit of the iTind system.
Secondary outcomes in the iTind group were also comparable to those for the UroLift. As shown in Table 8. below, the improvement of PFR (Omax) in the iTind group at 3 months was comparable to that observed in the LIFT study for UroLift. Patients in the iTind group also had smaller improvement in PVR but greater improvement in SHIM than the UroLift group at 3 months. The differences compared to UroLift were not statistically significant.
| Outcome Measurement | iTind | UroLift* | ||||
|---|---|---|---|---|---|---|
| n | Mean | SD | n | Mean | SD | |
| PFR/Qmax | 81 | 4.4 | 7.0 | 126 | 4.3 | 5.2 |
| PVR | 79 | -5.0 | 55.3 | 140 | -9.7 | 85.5 |
| SHIM/IIEF-5 | 84 | 0.4 | 7.0 | 132 | 0.1 | 5.8 |
Table 8. Comparing Outcome Measures between iTind and UroLift
- Roehrborn et al. 2013.
iTind MT-03 study results showed fewer adverse events compared to those reported in the pivotal study for UroLift. Table 9, below, compares the overall AEs and SAEs between iTind and UroLift.
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| iTind (N=118) | UroLift* (N=140) | |||
|---|---|---|---|---|
| No. Events | No. Subjects (%) | No. Events | No. Subjects (%) | |
| All AEs | 109 | 45 (38.1%) | 412 | 122 (87.1%) |
| Related AEs | 82 | 38 (32.2%)** | 247 | 113 (80.7) |
| Serious AEs | 16 | 10 (8.5%) | 25 | 16 (11.4) |
| Related SAEs | 5 | 3 (2.5%)** | 2 | 2 (1.4%) |
Table 9. Comparing AEs between iTind and UroLift
- Roehrbom et al. 2013. ** The numbers for related AEs and SAEs for iTind included events that were determined to be related or possibly related to the device or the procedure. The numbers represent the worst-case estimates. For UroLift, it is unclear from the published article whether the related AEs and SAEs include possibly related events.
As shown in the table, above, iTind treated patients had fewer AEs compared to patients treated with UroLift. The SAE rate is also lower for iTind that for UroLift. Furthermore, when comparing the incidence rate for individual AE types, iTind also demonstrates a lower rate for almost all urinary disorders, as shown in Table 10, below.
| iTind (N=118) | UroLift* (N=140) | |
|---|---|---|
| % Subject | % Subject | |
| Dysuria | 22.9 | 35 |
| Hematuria | 13.6 | 26.4 |
| Micturition urgency | 5.1 | 9.3 |
| Incontinence | 3.4 | 7.9 |
| Urinary retention | 5.9 | 5.7 |
Table 10. Comparison of Urinary Adverse Events
- K130651 Decision Summary.
Conclusions
Clinical improvement was seen in patients for up to 12 months following 5-7-day iTind implantation. The study met one of the two co-primary endpoints and showed a statistically and clinically significant improvement of IPSS scores at 12 months compared to the baseline. For the other co-primary endpoint at 3 months, the iTind treatment group showed a trend toward significance when compared to the sham. Analyses of the secondary endpoints demonstrated positive treatment effects in the iTind group for all the tested clinical outcome measures. including urinary flow rate, bladder emptying, and male sexual health. The iTind treatment also showed an improvement in the patient's quality of life. Safety results demonstrated a favorable safety profile for the iTind device, with a low rate of serious adverse events. After the device removal, the AE rate decreased significantly. Most of the AEs observed in the study were anticipated and were mild. In addition, when compared to NeoTract UroLift, which is intended for permanent implantation, the iTind system showed fewer AEs and SAEs, and a lower rate for almost all urinary disorders.
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LABELING
The iTind System complies with the labeling requirements under 21 CFR 801.109 for prescription devices in the provided physician labeling. In addition, the labeling includes contraindications, warnings and precautions, clinical data on the device and specific instructions for the safe and effective use of the device. The labeling identifies the validated shelf life of the device. The labeling also indicates that if the sterile barrier has been compromised, the device must not be used.
RISKS TO HEALTH
Table 11 below identifies the risks to health that may be associated with use of a temporarilyplaced urethral opening system for symptoms of benign prostatic hyperplasia and the measures necessary to mitigate these risks.
| Identified Risks to Health | Mitigation Measures |
|---|---|
| Adverse tissue reaction | Clinical performance testing |
| Biocompatibility evaluation | |
| Labeling | |
| Infection | Clinical performance testing |
| Sterilization validation | |
| Shelf life testing | |
| Labeling | |
| Untreated symptoms due to device | |
| deployment failure | Clinical performance testing |
| Non-clinical performance testing | |
| Shelf life testing | |
| Labeling | |
| Bleeding, perforation, trauma, obstruction, | |
| incontinence, dysuria, urgency due to | |
| device failure or difficult removal | Clinical performance testing |
| Non-clinical performance testing | |
| Shelf life testing | |
| Labeling |
| Table 11. Identified Risks to Health and Mitigation Measures | |||
|---|---|---|---|
SPECIAL CONTROLS
In combination with the general controls of the FD&C Act, the temporarily-placed urethral opening system for symptoms of benign prostatic hyperplasia is subject to the following special controls:
-
- Clinical performance testing with the device under anticipated conditions of use must evaluate improvement in urinary outflow symptoms and document the adverse event profile.
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-
- The patient-contacting components of the device must be demonstrated to be biocompatible.
- Performance data must demonstrate the sterility of the patient-contacting components of 3. the device.
-
- Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
- న. Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
- Deployment and removal; and a)
- b) Mechanical strength.
-
- Labeling must include:
- Instructions for use, including the recommended training for safe use of the a) device:
- A summary of the clinical performance testing conducted with the device, b) including device- and procedure-related adverse events; and
- c) A shelf life.
BENEFIT/RISK DETERMINATION
The benefits and risks of the iTind System when used to treat symptoms due to urinary outflow obstruction secondary to benign prostatic hyperplasia (BPH) in men age 50 and above are based on non-clinical and clinical data.
The benefits of the iTind System include a clinically meaningful decrease in urinary outflow obstruction symptoms and an increased quality of life sustained to 12 months, as demonstrated by reduced IPSS and QoL scores, respectively. The insertion and retrieval procedures are minimally invasive, each performed via cystoscopy. The iTind implant is temporary, residing at the prostatic urethra for a duration of 10-point reductions in IPSS from baseline to follow-up at 3 and 12 months, and an improvement in QoL score by almost two points, though this outcome was similar between groups. In two outside-U.S. (OUS), single-arm, investigational studies, subjects demonstrated a > 10-point improvement in IPSS at 12 months and, in one of the studies, a ≥ 3-point improvement in IPSS at 36 months.
Benefit/Risk Conclusion
In conclusion, given the available information above, the data support that, for use of the iTind System for the treatment of symptoms due to urinary outflow obstruction secondary to benign prostatic hyperplasia (BPH) in men age 50 and above, the probable benefits outweigh the probable risks. The device provides benefits and the risks can be mitigated by the use of general controls and the identified special controls.
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CONCLUSION
The De Novo request for the Medi-Tate iTind System is granted and the device is classified under the following:
Product Code: QKA Device Type: Temporarily-placed urethral opening system for symptoms of benign prostatic hyperplasia Class: II Regulation: 21 CFR 876.5510