(137 days)
The Exablate Prostate System is indicated for endorectal MR-Guided Focused Ultrasound (MRgFUS) ablation of Prostatic Tissue.
The proposed Exablate 2100 / 2100V1 Type 3 Prostate System (Trademark Name: Exablate Prostate System) is a high intensity Magnetic Resonance ("MR") image- guided focused ultrasound (MRgFUS) system intended for endorectal use that delivers focused ultrasound energy into the prostate in a minimally invasive manner by utilizing anendorectal probe transducer.
The Exablate Prostate System combines a multiple-channel phased-array Focused Ultrasound (FUS) transducer probe and magnetic resonance imaging (“MRI”) in a closed-loop treatment for the thermal procedure of Prostatic Tissue while monitoring the procedure in real time.
The Exablate Prostate System is designed to work in conjunction with FDA cleared 1.5Tand 3.0T MRI scanners with phased array torso cardiac coils that is used for guidance andprocedure monitoring and control feedback. The Exablate Prostate System is fully integrated with the MRI scanner used to provide MR images of the patient's anatomy and prepare an appropriate procedure plan. Measured tissue temperature changes provide feedback on the procedure dose in the targeted area and its surroundings, allowing real-time monitoring to achieve safe and effective outcomes.
The intended users for the Exablate Prostate System are trained and certified physicians and/or technicians (clinicians) who are seeking to offer patients an incisionless, focal, and MR guided and controlled prostate tissue ablation and have successfully completed the Insightec Exablate training to operate the device.
The Exablate Prostate System platform is intended to ablate prostatic tissue with focused ultrasound and operates in conjunction with FDA cleared compatible MRI scanners for the purposes of real time procedure planning, MR based guidance of the focused ultrasound energy to the target region, MR thermal imaging and ablation monitoring. The procedure effect of the Exablate Prostate System is achieved by accurately guiding the focus of the ultrasound energy to the target region. The energy is then repeatedly transmitted to the target until the desired outcome is achieved. The targeted area is defined based on MR images taken during the procedure, while patient is in procedure position. The procedure is constantly monitored in a real-time closed-loop MR thermal feedback. Once the targeting is complete, the outcome is confirmed with adequate post-procedure MR imaging sequences.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Endpoint) | Reported Device Performance (Exablate Prostate System) |
|---|---|
| Safety Endpoints (Primary) | |
| No Serious Adverse Events (SAEs) | No SAEs reported |
| No Life-threatening Adverse Events (AEs) | No Life-threatening AEs reported |
| Majority of AEs Mild or Moderate | 99.5% of AEs Mild (86.5%) or Moderate (13%) |
| Most events resolved within 90 days or less | 63.5% resolved within 90 days |
| Number of device-related AEs unresolved at 12 months | 32 (16%) |
| Effectiveness Endpoints (Primary) | |
| Negative biopsy within area of treatment at 6 months | 91.1% negative biopsies (n=92/101) |
| Reduction in PSA value at 6 months | 91.1% of subjects showed a decrease in PSA (n=92/101) |
| Non-Perfused Volume (NPV) covered targeted Gleason Grade Group (GGG) tissue at treatment | 87.1% of subjects showed NPV covered targeted GGG tissue (n=88/101) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 101 male subjects.
- Data Provenance:
- Country of Origin: United States.
- Retrospective or Prospective: Prospective, single-arm clinical study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The document does not explicitly state the number of experts used to establish the ground truth for the test set or their specific qualifications. However, it indicates:
- "MRI-visible, hemilateral lesion of biopsy proven Gleason Grade Group 2 (3+4) or 3 (4+3) adenocarcinoma" – This implies that a pathologist (expert) would have reviewed the biopsies to determine the Gleason Grade Group, which serves as a form of ground truth for disease presence and severity.
- "physician targeted prostate tissue" and "clinical study was conducted in accordance with Good Clinical Practice, Insightec Standard Operating Procedures and FDA 21 CFR 50, 54, 56 and 812" – This suggests that medical professionals (likely including radiologists for MRI interpretation and urologists for treatment planning and clinical assessment) were involved in defining the target area and evaluating outcomes.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (like 2+1, 3+1). The "biopsy proven" and "physician targeted" phrases suggest that standard clinical practice and expert interpretation were used, but no specific adjudication process for controversial cases is detailed.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study solely evaluated the performance of the Exablate Prostate System without comparing it to human readers with or without AI assistance. The study is an evaluation of the device's clinical performance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
The Exablate Prostate System is a High Intensity Focused Ultrasound (HIFU) system that requires human operators (trained and certified physicians and/or technicians). It is not an "algorithm only" device. The system aids human operators by providing "real time-controlled ablation of prostate tissue" and "MR based guidance of the focused ultrasound energy to the target region, MR thermal imaging and ablation monitoring." Therefore, a standalone (algorithm only) performance evaluation would not be applicable, as human interaction is integral to its intended use.
7. The Type of Ground Truth Used
The ground truth used for the effectiveness endpoints was:
- Pathology/Histology: For the "biopsy results," the presence or absence of Gleason Grade Group tissue was determined via biopsy, which is a pathology-based ground truth.
- Clinical/Biomarker Data: For "reduction in PSA value," blood test results (PSA levels) served as the ground truth.
- Imaging-based Assessment: "Non-Perfused Volume (NPV) covering physician targeted prostate tissue at treatment" was likely assessed using post-treatment MR imaging, interpreted by medical professionals.
8. The Sample Size for the Training Set
The document does not provide information regarding a separate training set or its sample size. The study described is a prospective clinical trial for evaluating the device's safety and effectiveness in a clinical population. If the device incorporates AI/ML components that require training, that information is not detailed in this summary.
9. How the Ground Truth for the Training Set Was Established
Since information about a training set is not provided, the method for establishing ground truth for a training set is also not described in this document.
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November 23, 2021
Insightec, Inc. Nadir Alikacem, Ph.D. VP of Global Regulated Clinical Affairs 4851 LBJ Freeway, Suite 400 Dallas, TX 75244
Re: K212150
Trade/Device Name: Exablate Prostate System Regulation Number: 21 CFR§ 876.4340 Regulation Name: High Intensity Ultrasound System For Prostate Tissue Ablation Regulatory Class: II Product Code: PLP Dated: October 27, 2021 Received: October 28, 2021
Dear Nadir Alikacem:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies.
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You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatoryinformation/postmarketing-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Mark J. Antonino, M.S. Assistant Director DHT3B: Division of Reproductive. Gynecology and Urology Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name Exablate Prostate System
Indications for Use (Describe)
The Exablate Prostate System is indicated for endorectal MR-Guided Focused Ultrasound (MRgFUS) ablation of Prostatic Tissue
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
Form Approved: OMB No. 0910-0120
Expiration Date: 06/30/2020
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5. 510(k) Summary
| Submitter: | Insightec, Ltd.5 Nachum Heth St.PO Box 2059, Tirat Carmel 39120Israel |
|---|---|
| Regulatory ContactPerson: | Insightec, Inc.Nadir Alikacem, PhDVP of Global Regulated ClinicalAffairs4851 LBJ Freeway, Suite400Dallas TX 75244 |
| Date Prepared: | November 18, 2021 |
| Proposed Device: | Manufacturer: Insightec, LtdTrade Name: Exablate Prostate SystemCommon Name: High Intensity Focused Ultrasound SystemClassification Name: High Intensity Ultrasound System for Prostate Tissue AblationProduct Code: PLPRegulatory Number: 21 CFR 876.4340Regulatory Class: II |
| Predicate Device: | 510(k) Number: K160942,Manufacturer: SonaCare Medical, LLCTrade Name: SONABLATECommon Name: High Intensity Focused Ultrasound SystemClassification Name: High Intensity Ultrasound System for Prostate Tissue AblationProduct Code: PLPRegulatory Standard: 21 CFR 876.4340Regulatory Class: II |
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| Device Description: | The proposed Exablate 2100 / 2100V1 Type 3 Prostate System (TrademarkName: Exablate Prostate System) is a high intensity Magnetic Resonance("MR") image- guided focused ultrasound (MRgFUS) system intended forendorectal use that delivers focused ultrasound energy into the prostate in aminimally invasive manner by utilizing anendorectal probe transducer.The Exablate Prostate System combines a multiple-channel phased-array FocusedUltrasound (FUS) transducer probe and magnetic resonance imaging (“MRI”) in aclosed-loop treatment for the thermal procedure of Prostatic Tissue whilemonitoring the procedure in real time.The Exablate Prostate System is designed to work in conjunction with FDAcleared 1.5Tand 3.0T MRI scanners with phased array torso cardiac coils that isused for guidance andprocedure monitoring and control feedback. The ExablateProstate System is fully integrated with the MRI scanner used to provide MRimages of the patient's anatomy and prepare an appropriate procedure plan.Measured tissue temperature changes provide feedback on the procedure dose inthe targeted area and its surroundings, allowing real-time monitoring to achievesafe and effective outcomes.The intended users for the Exablate Prostate System are trained and certified physiciansand/or technicians (clinicians) who are seeking to offer patients an incisionless, focal, andMR guided and controlled prostate tissue ablation and have successfully completed theInsightec Exablate training to operate the device.The Exablate Prostate System platform is intended to ablate prostatic tissue with focusedultrasound and operates in conjunction with FDA cleared compatible MRI scanners forthe purposes of real time procedure planning, MR based guidance of the focusedultrasound energy to the target region, MR thermal imaging and ablation monitoring. Theprocedure effect of the Exablate Prostate System is achieved by accurately guiding thefocus of the ultrasound energy to the target region. The energy is then repeatedlytransmitted to the target until the desired outcome is achieved. The targeted area is definedbased on MR images taken during the procedure, while patient is in procedure position.The procedure is constantly monitored in a real-time closed-loop MR thermal feedback.Once the targeting is complete, the outcome is confirmed with adequate post-procedureMR imaging sequences. |
|---|---|
| Indications forUse: | The Exablate Prostate System is indicated for endorectal MR-Guided Focused Ultrasound(MRgFUS) ablation of Prostatic Tissue. |
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Summary of Technological Characteristics:
Comparisons with the predicate devise show the technological characteristics of the proposed Exablate Prostate System to be substantially equivalent to the predicate device. The proposed device is functionally identical to the predicate device.
The major differences between the proposed and predicate device are identified in the following table. No other technological changes have been made to the proposed device.
| (New Device) | (Predicate Device) | |
|---|---|---|
| Model | Exablate Prostate System | SONABLATE |
| 510(k)Submitter | Insightec | Sonablate Medical, LLC |
| 510(k)Number | K212150 | K160942 |
| Product code | PLP | PLP |
| Indications forUse | The Exablate Prostate System is indicatedfor endorectal MR-Guided FocusedUltrasound (MRgFUS) ablation ofProstatic Tissue. | The Sonablate® is indicated fortransrectal high intensity focusedultrasound (HIFU)ablation of prostatic tissue |
| Prescriptionuse | Yes | Yes |
| Minimallyinvasive | Yes | Yes |
| Outpatientprocedures | Yes | Yes |
| Anesthesiarequired | Yes | Yes |
| Physiciantrainingrequired | Yes | Yes |
| SystemComponents | Console/Workstation Patient Table Exablate Probe Equipment Cabinet Water System Cabinet Cleaning and HLD Cart Disposable accessories | Control module Endorectal probe Computer and peripherals Cooling fluid Probe moment assembly and holder Disposable accessories |
| PatientPosition | Lithotomy | Lithotomy |
| Imagingmodality forlocalization,procedure andcontrol | MR Imaging | Ultrasound |
| Probe Type | Phased Array | Linear Mechanical |
| TherapyFrequency | $2.3\pm0.2$ MHz | $4$ MHz |
| LongitudinalMotion | $5$ cm | $4.5$ cm |
| Image Size | $28$ x $28$ cm | $4.5$ cm x $6.25$ cm |
| Field of View | 90° | 112° |
| AblationModality | HIFU | HIFU |
| AblationFrequency | $2.3\pm0.2$ MHz | $4.0$ MHz |
| Focal Distance | $1.5-6.0$ cm | $3.0\pm0.1$ cm$4.0\pm0.1$ cm |
| Probe Length | 9.5 cm | 5.9cm |
| ProbeDiameter | 3.1 cm | 3.3 cm |
| Probe NeckDiameter | 1.8 cm | 1.8 cm |
| Duty Cycle | NA (up to the physician) | 3 seconds “on” and 5 seconds “off” |
| HIFU TotalAcousticPower | 0-30W | 0-28 W, 24 W typical (3.0 cm focallength transducer) 0-40 W, 37 W typical(4.0 cm focal length transducer) |
| Lesion height | 0.8-4.0 cm | 1.0 cm |
| Longitudinallesion spacing | 3.0 mm | 3.0 mm |
| Transverselesion spacing | 3-4° | 3° |
| Ablationplanning | In longitudinal and transverse planes | In longitudinal and transverse planes |
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The following non-clinical studies were conducted on the Exablate Prostate Summary of Non-System to support substantial equivalence to the predicate device: Clinical /Testing:
- -Bioburden testing of the rectal balloon component
- -Reprocessing validation studies on the reusable endorectal probe
- -Package integrity testing of the kit containing single use components
- -Biocompatibility studies on the rectal balloon component were demonstrated in accordance with ISO 10993 standards as follows:
- Cytotoxicity [ISO 10993-5:2009] [ISO 10993-12:2008] o
- Sensitization [ISO 10993-12:2008] o
- Irritation / Intracutaneous Reactivity [ISO 10993-10-2002] O [ISO 10993-12:2008]
- Software verification and validation testing were demonstrated in । accordance with the FDA's "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" guidance documented issued on May 11, 2005
- । Electrical safety and electromagnetic compatibility testing were demonstrated in accordance with the following standards:
- SII, 60601-1-2 O
- SII, 60601-2-62 O
- SII, 60601-1 + 62304 O
- o SII, 60601-1-6
- Bench tests to characterize the device's acoustic output, verify MR safety, image quality, targeting accuracy and thermal monitoring,
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and verify the performance of hardware functions
Animal study (canine prostate model) to demonstrate that the device thermally ablates targeted tissue without thermal injury to adjacent, nontarget tissues
The Insightec MRgFUS utilizes a non-invasive thermal ablation integrated with a Summary of Clinical MRImaging system that allowed real time-controlled ablation of prostate tissue Data: within thestudy. This technology resulted in the successful safety and effectiveness endpoint outcomes reported.
The study in support of the submission was conducted as a multi-center in the United States, prospective, single arm where subjects were treated and followed for 12 months.
One-hundred and one (101) males over 50 years of age (median age of 63 years) with a single, MRI-visible, hemilateral lesion of biopsy proven Gleason Grade Group 2 (3+4) or 3 (4+3) adenocarcinoma and with a PSA less than or equal to 20 ng/mL were treated with the Exablate 2100 Prostate System. The median prostate lesion volume was 1.7 cm3. It should be noted the median planned Region of Treatment (ROT) was approximately 3.4 cm³.
The study's primary endpoints are 12 Months for safety and 6 Months for effectiveness. The safety analysis included all subjects who received at least one sonication of Exablate treatment, with Adverse Events documented and reported by the investigational sites throughout the subject's participation in the study. The effectiveness analysis included all subjects who completed at least one Exablate treatment, with the primary effectiveness endpoints being biopsy at 6-months, reduction in PSA value at 6 months, and non-perfused volume (NPV) covering physician targeted prostate tissue at treatment. The clinical study was conducted in accordance with Good Clinical Practice, Insightec Standard Operating Procedures and FDA 21 CFR 50, 54, 56 and 812.
Safety Analysis
There were no Serious Adverse Events (SAEs) or Life-threatening AEs reported in this study, with only 1 AE was categorized as Severe for an UTI event resolving in less than a week. The vast majority (99.5%) of AEs reported were either Mild (n=173, 86.5%) or Moderate (n=26, 13%). Overall, 70 subjects (69.3%) of all subjects reported at least one AE, with 67 subjects (66.3%, 95% CI 56.25-75.44) reporting at least one event that was deemed related to the Exablate procedure or device.
Overall, 57 subjects had one or more neurovascular bundle and/or their urethra included within their treatment, while 44 did not have any critical structures included with their treatment volume.
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| Table 1. Exablate Device- or Procedure-Related AEs | ||||
|---|---|---|---|---|
| Coded AE Term | Number of Events | Number of Subjects | Unresolved at 12 Months (*Frequency) | Unresolved at 12 Months (**Frequency) |
| Hematuria | 25 | 24 (24%) | 0 (0%) | 0 (0%) |
| Urinary incontinence | 21 | 19 (19%) | 7 (3.5%) | 7 (7%) |
| Erectile dysfunction | 19 | 19 (19%) | 16 (8.0%) | 16 (16%) |
| Urinary retention | 17 | 15 (15%) | 0 (0%) | 0 (0%) |
| Penile/ testicular pain | 15 | 14 (14%) | 0 (0%) | 0 (0%) |
| Hematospermia | 13 | 13 (13%) | 1 (0.5%) | 1 (1%) |
| Fatigue | 10 | 9 (9%) | 0 (0%) | 0 (0%) |
| Ejaculation disorder | 9 | 9 (9%) | 2 (1.0%) | 2 (2%) |
| Urinary frequency | 9 | 9 (9%) | 2 (1.0%) | 2 (2%) |
| Urinary tract pain | 6 | 6 (6%) | 0 (0%) | 0 (0%) |
| Urinary hesitancy | 6 | 6 (6%) | 1 (0.5%) | 1 (1%) |
| Urinary urgency | 6 | 6 (6%) | 1 (0.5%) | 1 (1%) |
| Constipation/ bloating | 3 | 3 (3%) | 0 (0%) | 0 (0%) |
| Diarrhea | 3 | 3 (3%) | 0 (0%) | 0 (0%) |
| Groin/pelvic/ suprapubic pain | 3 | 3 (3%) | 0 (0%) | 0 (0%) |
| Bladder spasm | 3 | 3 (3%) | 0 (0%) | 0 (0%) |
| Edema limbs | 2 | 2 (2%) | 0 (0%) | 0 (0%) |
| Urinary tract infection | 2 | 2 (2%) | 0 (0%) | 0 (0%) |
| Anal/rectal pain | 2 | 2 (2%) | 0 (0%) | 0 (0%) |
| Hemorrhoidal hemorrhage | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Proctitis | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Allergic reaction | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Vertigo | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Testicular infection | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Paresthesia | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Positional pain | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Prostatic pain | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Orchitis | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Prostatic cyst | 1 | 1 (1%) | 1 (0.5%) | 1 (1%) |
| Bullousdermatitis | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| Urethrastricture | 1 | 1 (1%) | 1 (0.5%) | 1 (1%) |
| Deep veinthrombosis | 1 | 1 (1%) | 0 (0%) | 0 (0%) |
| *n= 200 AEs occurred in cohort 2 | ||||
| **N=101 subjects in cohort 2 |
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Most events resolved in 90 days or less (n=127, 63.5%) with 46 (23%) resolving within a week. There were no ongoing AEs noted as severe or life threatening and 23% of the AEs were transient in nature and resolved within 7 days. There were 121 out of the 187 (Table 1) Exablate procedure- or devicerelated adverse events (64.5% of all Exablate procedure- or device-related events, 95% CI 57.40-71.54) that self-resolved, without any actions taken to date.
There were 32 (16%) Exablate procedure- or device-related adverse events that were unresolved at 12 months. Of these, erectile dysfunction and urinary incontinence were the highest recorded events at 8% and 3.5%, respectively. The rest of the unresolved AEs at 24 months were under 1% which include ejaculation disorder, urinary frequency, hematospermia, urinary hesitancy, urinary urgency, prostate cyst, and urethra stricture.
Additional adverse events have been reported previously in the literature for whole-gland or focal prostate ablation therapies but were not observed in this study through 12 months. These include urinary events such as urinary tract obstruction, bladder neck contracture, urinary fistula, urinary tract or kidney stones, urethral sloughing/discharge/debris in urine, hydronephrosis, and urinoma. Gastrointestinal events that have been reported, but not observed in this study consist of rectal fistula, small intestine obstruction, bowl injury including anal tears, inguinal hernia, upper gastrointestinal hemorrhage, and diverticulitis. Additional reproductive events that have been reported include prostate infection, testicular disorder or epididymitis, and decreased libido. Other general events reported in focal or whole gland prostate ablation therapies include hypotension, hypertension, fever, anemia, syncope, indigestion, and osteomyelitis.
Efficacy Analysis
The first primary effectiveness endpoint is within area of treatment prostate biopsy occurring at 6-months post-treatment. Positive biopsy was defined as any Gleason Grade Group tissue identified within the area of planned Exablate treatment. The majority (n=92, 91.1%) of subject biopsies were negative within the area of treatment. This data is shown in Table 2 below.
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| Table 2. Biopsy Results of Any GGG Tissue Within the Planned ROT at6 Months | ||||||||
|---|---|---|---|---|---|---|---|---|
| Biopsy Results Withinthe Planned ROT | Exablate | Lower 95%Confidence | Upper 95%Confidence | |||||
| N | % | Interval | Interval | |||||
| Positive | 9 | 8.9 | 4.2% | 16.2% | ||||
| Negative | 92 | 91.1 | 83.8% | 95.8% | ||||
| Total | 101 | 100.0 |
The second primary effectiveness endpoint is reduction in PSA value from baseline to 6-months post-treatment. PSA values that increased or remained the same were considered an increase. The vast majority (n=92, 91.1%) of subjects showed a decrease in PSA at 6-months. This data is shown below in Table 3.
| Table 3. Reduction in PSA Value at 6 Months | ||||
|---|---|---|---|---|
| Reduction in PSA Value at 6 Months | Exablate | Lower 95% Confidence Interval | Upper 95% Confidence Interval | |
| N | % | |||
| Yes | 92 | 91.1 | 83.8% | 95.8% |
| No | 9 | 8.9 | 4.2% | 16.2% |
| Total | 101 | 100.0 |
The final primary effectiveness endpoint is Non-Perfused Volume (NPV) coverage of targeted Gleason tissue at treatment. The majority (n=88, 87.1%) of subjects showed that the NPV covered targeted Gleason Grade Group (GGG) tissue following treatment. This data is shown below in Table 4.
| Table 4. NPV Covered Target Gleason Grade Group (GGG) Tissue atTreatment | ||||
|---|---|---|---|---|
| NPV CoveredTargeted GGG Tissue | Exablate | Lower 95%ConfidenceInterval | Upper 95%ConfidenceInterval | |
| N | % | |||
| Yes | 88 | 87.1 | 79.0% | 93.0% |
| No | 13 | 12.9 | 7.0% | 21.0% |
| Total | 101 | 100.0 |
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The safety profile for this study is favorable on its own as well as compared tothe predicate device. There have been no life threatening nor unanticipated events, and noSAEs reported. Of those events commonly reported with the MRgFUS procedure, the frequency identified for Exablate tends to be lower with most events resolving within 90 days. Moreover, other than one Severe event that was not related to the Exablate device, all others were either Mild or Moderate.
Effectiveness data, especially that of the biopsy results showing a 91% negative result within the area of procedure compared to a 76% negative rate, is considerably betterthan the predicate comparator. On the other hand, the PSA decreased from baseline of 91% compared to 93% at 6-months, which is in-line with the predicate.
In conclusion, it is evident that Insightec's Exablate MR Guided therapy for ablation of prostate tissue is not only comparable, but in most instances' superior to that of data from the predicate device.
Conclusions
This data supports the substantial equivalence of the Exablate Prostate System to its predicate and demonstrates safety and effectiveness of the device for the ablation of prostate tissue.
The subject and predicate devices have the same intended use. Although there Conclusion: are differences in technological characteristics between the subject and predicate devices, these differences do not raise different questions of safety or effectiveness. The clinical and non-clinical performance data demonstrate that the subject device is substantially equivalent to the predicate device.
§ 876.4340 High intensity ultrasound system for prostate tissue ablation.
(a)
Identification. A high intensity ultrasound system for prostate tissue ablation is a prescription device that transmits high intensity therapeutic ultrasound energy into the prostate to thermally ablate a defined, targeted volume of tissue, performed under imaging guidance. This classification does not include devices that are intended for the treatment of any specific prostate disease and does not include devices that are intended to ablate non-prostatic tissues/organs.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Non-clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Characterization of acoustic pressure and power output at clinically relevant levels;
(ii) Measurement of targeting accuracy and reproducibility of high intensity ultrasound output;
(iii) Ultrasound-induced heating verification testing at target and non-target tissues;
(iv) Electrical safety testing; and
(v) Electromagnetic compatibility testing.
(2) Software verification, validation, and hazard analysis must be performed.
(3) The elements of the device that may contact the patient's mucosal tissue must be demonstrated to be biocompatible.
(4) Performance data must demonstrate the sterility of the device components that contact the patient's mucosal tissue.
(5) Performance data must support shelf life by demonstrating continued sterility of the device or the sterile components, package integrity, and device functionality over the identified shelf life.
(6) Performance data must support the instructions for reprocessing all reusable components.
(7)
In vivo testing must demonstrate that the device thermally ablates targeted tissue in a controlled manner without thermal injury to adjacent, non-target tissues.(8) Clinical testing must document the adverse event profile, provide evidence of prostatic ablation, and demonstrate that the device performs as intended under anticipated conditions of use.
(9) Training must be provided so that upon completion of the training program, the physician can:
(i) Use all safety features of the device;
(ii) Accurately target the high intensity ultrasound energy within the desired region of the prostate; and
(iii) Perform the ablation procedure in a manner that minimizes damage to non-target tissues.
(10) Labeling must include:
(i) A section that summarizes the clinical testing results, including the adverse event profile and evidence of prostate ablation achieved; and
(ii) An expiration date or shelf life for single use components.