(101 days)
Not Found
No
The description focuses on "closed-loop process control software" that uses real-time data to adjust parameters, which is a form of automated control, not necessarily AI/ML. There is no mention of learning, training data, or typical AI/ML terminology.
Yes.
The device is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue, which is a therapeutic intervention aimed at treating medical conditions by ablating tissue.
No
This device is designed for the thermal ablation of prostate tissue, which is a therapeutic intervention, not a diagnostic one. While it uses diagnostic imaging (MRI) for guidance and monitoring, its primary function is treatment.
No
The device description explicitly states that the TULSA-PRO system consists of both hardware and software components, and details the function of hardware components like the Ultrasound Applicator and Endorectal Cooling Device.
Based on the provided information, the TULSA-PRO System is not an In Vitro Diagnostic (IVD) device.
Here's why:
- IVD Definition: In Vitro Diagnostic devices are used to examine specimens (like blood, urine, or tissue) taken from the human body to provide information about a person's health. This testing is done outside the body (in vitro).
- TULSA-PRO System Function: The TULSA-PRO System is used to treat prostate tissue within the body (in vivo) using ultrasound ablation guided by real-time MRI. It does not analyze samples taken from the patient.
The device description clearly outlines a therapeutic procedure performed directly on the patient's prostate tissue, not a diagnostic test performed on a sample.
N/A
Intended Use / Indications for Use
The TULSA-PRO System is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue.
Product codes
PLP
Device Description
The TULSA-PRO system combines real-time Magnetic Resonance (MR) imaging and MR thermometry with transurethral directional ultrasound and closed-loop process control software to deliver precise thermal ablation of a customized volume of physician prescribed prostate tissue. The system consists of both hardware and software components.
Transurethral ultrasound ablation (TULSA) treatment ablates prostate tissue using in-bore real-time MRI treatment planning, monitoring, visualization, and active temperature feedback control. The closed-loop features of the TULSA-PRO software use a real-time MRI interface to process MRI prostate temperature measurements, and communicate with the TULSA-PRO hardware, thereby controlling frequency, power and rotation rate of ultrasound to ablate physician prescribed prostate tissue with a high degree of precision.
The physician inserts two catheters, one transurethral and another transrectal, into the patient before he is moved into the MR bore. The transurethral catheter consists of an Ultrasound Applicator (UA) which delivers energy from the urethra outwards into the prostate tissue, heating it to thermal coagulation. The transrectal catheter is an Endorectal Cooling Device (ECD) which does not emit any energy, and cools the rectal wall adjacent to the prostate. Both catheters have fluid flowing inside throughout the treatment to thermally protect the urethra and rectum, in order to minimize the potential of any thermal damage to either the urinary or rectal pathways. The physician uses the TULSA-PRO console to robotically position the UA in the prostate and plan the treatment by contouring the prescribed tissue on realtime high-resolution cross-sectional MR images of the prostate. These features provide the physician with the ability and the control to customize the treatment plan to minimize thermal impact to critical structures surrounding the prostate including the external urethral sphincter, rectum and neurovascular bundles. The treatment begins based upon the physician's instructions by enabling the software to initiate thermal ablation. The TULSA-PRO closed-loop process control software reads real-time MR thermometry measurements and adjusts automatically and dynamically the frequency, power and rotation rate of ultrasound provided by each UA transducer, to deliver precise ablation of the prescribed prostate tissue. The software controls automated, continuous and robotic rotation of the transurethral UA by 360 degrees in sync with the process controlled delivery of thermal heating to all the intended regions of the prostate. Following completion of the ablation process, the two catheters are removed from the natural orifices of the patients.
Mentions image processing
The closed-loop features of the TULSA-PRO software use a real-time MRI interface to process MRI prostate temperature measurements, and communicate with the TULSA-PRO hardware, thereby controlling frequency, power and rotation rate of ultrasound to ablate physician prescribed prostate tissue with a high degree of precision.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Magnetic Resonance (MR) imaging
Anatomical Site
Prostate tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Physician / Not Found
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)
Clinical Data: The TULSA-PRO has been evaluated in prospective clinical trials, including the TACT Pivotal Study which was designed to determine the safety and effectiveness of the device according to the proposed intended use.
Sample size: 115 patients
Study type: Prospective Clinical Trials (TACT Pivotal Study)
Key results:
Safety: All Adverse Events (AE) were documented during the TACT study regardless of their attribution to the TULSA-PRO procedure. All AE's were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) developed by the NCI and were standardized to medical terminology using the Medical Dictionary for Regulatory Activities (MedDRA). To 12 months, there was no rectal injury or fistula, and no severe urinary incontinence or erectile dysfunction. There were no Grade 4 or higher AE related or possibly related (attributable) to TULSA-PRO.
Effectiveness: Prostate Volume Reduction: 106 of 115 patients had MR image data prior to and after TULSA (at 12 months). The median (IQR) perfused prostate volume of patients in TACT decreased 91.4% from 37.3 (27.2 – 47.6) cc pre-treatment to 2.8 (1.7 – 4.7) cc at 12 months on MRI.
PSA Reduction: Primary endpoint of PSA reduction ≥75% was achieved in 110 of 115 (96%) patients. Mean (95% confidence interval) PSA reduction to nadir was 92% (90 – 94%). Median (IQR) PSA reduction was 95% (91 – 98%) to nadir of 0.34 (0.12 – 0.56) ng/ml.
Prostate Biopsy at 12 months: Of 115 patients, 72 (63%) had a complete histological response with no evidence of any cancer (95% confidence interval: 54 – 71%) using an intent-to-treat analysis.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Primary efficacy endpoint: proportion of patients achieving a post-treatment PSA reduction ≥ 75% of their pre-treatment baseline value. (Achieved in 110 of 115 (96%) patients)
Mean (95% confidence interval) PSA reduction to nadir: 92% (90 – 94%)
Median (IQR) PSA reduction: 95% (91 – 98%) to nadir of 0.34 (0.12 – 0.56) ng/ml
Median (IQR) perfused prostate volume reduction: 91.4% (from 37.3 (27.2 – 47.6) cc pre-treatment to 2.8 (1.7 – 4.7) cc at 12 months on MRI)
Mean and 95% confidence interval of the prostate volume reduction: 89% (87 – 91%)
Complete histological response with no evidence of any cancer (ITT): 72 (63%) of 115 patients (95% confidence interval: 54 – 71%).
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left and the FDA acronym and name on the right. The FDA acronym and name are in blue, with the acronym in a larger font size than the name. The name is written as "U.S. FOOD & DRUG ADMINISTRATION".
August 15, 2019
Profound Medical Inc. Goldy Singh VP, Clinical and Regulatory Affairs 2400 Skymark Avenue, Unit #6 Mississauga Ontario L4W5K5 CANADA
Re: K191200
Trade/Device Name: TULSA-PRO System Regulation Number: 21 CFR 876.4340 Regulation Name: High Intensity Ultrasound System for Prostate Tissue Ablation Regulatory Class: Class II Product Code: PLP Dated: July 16, 2019 Received: July 17, 2019
Dear Goldy Singh:
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
1
statutes and regulations administered by other Federal agencies. 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-regulatory-information/postmarketing-safety-reportingcombination-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 medical devices and radiation-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,
for Glenn B. Bell, Ph.D. Assistant Division 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
2
Indications for Use
510(k) Number (if known) K191200
Device Name TULSA-PRO SYSTEM
Indications for Use (Describe)
The TULSA-PRO System is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/3/Picture/1 description: The image shows the logo for Profound Medical Inc. The logo is in blue and features the word "PROFOUND" in large, bold letters. Below the word "PROFOUND" is the word "MEDICAL" in smaller, bold letters, followed by "Inc." in even smaller letters. There is a horizontal line going through the letters of the word "PROFOUND".
510(k) Summary
l. General Information
- ' Applicant Name: Profound Medical Inc. 2400 Skymark Avenue, Unit #6, Mississauga, ON L4W 5K5, Canada T: 647.476.1350 F: 647.847.3739
- 트 Regulatory contact: Goldy Singh VP Clinical & Regulatory Affairs 2400 Skymark Avenue, Unit #6, Mississauga, ON L4W 5K5, Canada Phone: 647.476.1350 × 403 Fax: 647.847.3739 Email: gsingh@profoundmedical.com
- ' Date Prepared: 2 Aug 2019
ll. Device Identification
- 트 Proprietary Name: TULSA-PRO System
- ' Common Name: High Intensity Ultrasound System for Prostate Tissue Ablation
- ' Regulatory Class: Class II
- Regulation Name: High Intensity Ultrasound System for Prostate Ablation
- I Regulation Number: 21 CFR 876.4340
- ' Product Code: PLP (High Intensity Ultrasound System for Prostate Ablation)
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Image /page/4/Picture/1 description: The image contains the logo for Profound Medical Inc. The logo is in blue and consists of the word "PROFOUND" on the top line and the word "MEDICAL" on the bottom line. The letters "OU" in "PROFOUND" are connected by a horizontal line with a dot in the middle. The word "Inc." is in a smaller font size and is located to the right of the word "MEDICAL".
III. Predicate Device Information
| Predicate Device | Ablatherm Integrated Imaging |
|---|---|
| 510(k) Number | K153023 |
| Decision Date | Nov 6, 2015 |
| Manufacturer | EDAP Technomed, Inc. |
IV. Device Description
The TULSA-PRO system combines real-time Magnetic Resonance (MR) imaging and MR thermometry with transurethral directional ultrasound and closed-loop process control software to deliver precise thermal ablation of a customized volume of physician prescribed prostate tissue. The system consists of both hardware and software components.
Transurethral ultrasound ablation (TULSA) treatment ablates prostate tissue using in-bore real-time MRI treatment planning, monitoring, visualization, and active temperature feedback control. The closed-loop features of the TULSA-PRO software use a real-time MRI interface to process MRI prostate temperature measurements, and communicate with the TULSA-PRO hardware, thereby controlling frequency, power and rotation rate of ultrasound to ablate physician prescribed prostate tissue with a high degree of precision.
The physician inserts two catheters, one transurethral and another transrectal, into the patient before he is moved into the MR bore. The transurethral catheter consists of an Ultrasound Applicator (UA) which delivers energy from the urethra outwards into the prostate tissue, heating it to thermal coagulation. The transrectal catheter is an Endorectal Cooling Device (ECD) which does not emit any energy, and cools the rectal wall adjacent to the prostate. Both catheters have fluid flowing inside throughout the treatment to thermally protect the urethra and rectum, in order to minimize the potential of any thermal damage to either the urinary or rectal pathways. The physician uses the TULSA-PRO console to robotically position the UA in the prostate and plan the treatment by contouring the prescribed tissue on realtime high-resolution cross-sectional MR images of the prostate. These features provide the physician with the ability and the control to customize the treatment plan to minimize thermal impact to critical structures surrounding the prostate including the external urethral sphincter, rectum and neurovascular bundles. The treatment begins based upon the physician's instructions by enabling the software to initiate thermal ablation. The TULSA-PRO closed-loop process control software reads real-time MR thermometry measurements and adjusts automatically and dynamically the frequency, power and rotation rate of ultrasound provided by each
5
Image /page/5/Picture/1 description: The image contains the logo for Profound Medical Inc. The logo is in blue and features the company name in a bold, sans-serif font. The word "PROFOUND" is on the top line, and "MEDICAL Inc." is on the bottom line. There is a horizontal line going through the "O" in profound.
UA transducer, to deliver precise ablation of the prescribed prostate tissue. The software controls automated, continuous and robotic rotation of the transurethral UA by 360 degrees in sync with the process controlled delivery of thermal heating to all the intended regions of the prostate. Following completion of the ablation process, the two catheters are removed from the natural orifices of the patients.
V. Intended Use
The TULSA-PRO® System is indicated for transurethral ultrasound ablation (TULSA) of prostate tissue.
VI. Summary of Non-clinical testing
The following non-clinical testing was provided in support of this submission:
- . Bench Performance testing was conducted for the TULSA-PRO System to demonstrate that the system meets the requirements of the product design specification and performs in accordance with its intended use.
- Biocompatibility testing was conducted in accordance with ISO 10993-1:2018 Biological Evaluation of Medical Devices, Part 1: Evaluation and Testing within a Risk Management Process.
- . Software validation activities were performed in accordance with the FDA Guidance, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices."
- . Sterilization validation activities were performed in accordance with "ISO 11135 Second edition - Sterilization of health-care products - Ethylene oxide -Requirements for the development, validation and routine control of a sterilization process for medical devices."
- Electrical Safety and Electromagnetic Compatibility have been confirmed by a Nationally Recognized Testing Laboratory.
- Animal Studies – Animal studies were conducted on a canine prostate model.
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Image /page/6/Picture/1 description: The image shows the logo for Profound Medical Inc. The word "PROFOUND" is in large, blue, sans-serif font. There is a horizontal line going through the "O" in "PROFOUND". Below "PROFOUND" is the word "MEDICAL" in a smaller, blue, sans-serif font. To the right of "MEDICAL" is "Inc." in a smaller, blue, sans-serif font.
VII. Conformance to Recognized Standards
The TULSA-PRO System complies with applicable sections of the following recognized consensus standards:
- . IEC 60601-1:2005/A1:2012 – Medical electrical equipment – Part 1: General requirements for basic safety and essential performance
- IEC 60601-1-2 Edition 4.0 2014-02 Medical electrical equipment Part 1-2: . General requirements for basic safety and essential performance – Collateral Standard: Electromagnetic disturbances – Requirements and tests
- . IEC 60601-1-6 Edition 3.1 2013-10 – General requirements for basic safety and essential performance - Collateral standard: Usability
- ANSI/AAMI 62366-1 Edition 1.0 2015-02 Medical devices Part 1: Application ● of usability engineering to medical devices
- IEC 60601-1-8 Edition 2.1 2012-11 – Medical electrical equipment – Part 1-8: General requirements for basic safety and essential performance – Collateral Standard: General requirements, tests and guidance for alarm systems in medical electrical equipment and medical electrical systems
- . IEC 60601-1-10 Edition 1.1 2013-11 – Medical electrical equipment – Part 1-10: General requirements for basic safety and essential performance – Collateral Standard: Requirements for the development of physiologic closed-loop controllers
- . IEC 60601-2-62 Edition 1.0 2013-07- Medical Electrical Equipment - Part 2-62: Particular Requirements For The Basic Safety And Essential Performance Of High Intensity Therapeutic Ultrasound (HITU) Equipment
- . ISO 14971:2012 – Medical devices – Application of risk management to medical devices
- . ANSI/AAMI/IEC 62304 Edition 1.1 2015-06 – Medical device software – Software life cycle processes
- . ISO 10993-1 Fifth edition 2018-08 – Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process
- ISO 10993-4 Third edition 2017-04 – Biological evaluation of medical devices – Part 4: Selection of tests for interactions with blood
- ISO 10993-5 Third edition 2009-06-01 – Biological evaluation of medical devices – Part 5: Tests for in vitro cytotoxicity
- . ISO 10993-7 Second edition 2008-10-15 – Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals
- ISO 10993-10 Third Edition 2010-08-01 – Biological evaluation of medical devices – Part 10: Tests for irritation and skin sensitization
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Image /page/7/Picture/1 description: The image shows the logo for Profound Medical Inc. The logo is in blue and consists of the word "PROFOUND" in large, bold letters, with the word "MEDICAL" underneath in smaller letters. To the right of the word "MEDICAL" is the superscript "Inc.". There is a horizontal line going through the "O" in "PROFOUND" with a dot in the middle of the "O".
- ISO 10993-11 Third edition 2017-09 – Biological evaluation of medical devices – Part 11: Tests for systemic toxicity
- ISO 11135 Second edition 2014-07-15 – Sterilization of health-care products – Ethylene oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices
- . ANSI/AAMI/ISO 11607-1:2006/(R) 2010 – Packaging for terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier systems and packaging
- . ANSI/AAMI/ISO 11607-2:2006/(R) 2010 - Packaging for terminally sterilized medical devices – Part 2: Validation requirements for forming, sealing and assembly processes
- . ISO 11737-1 Third edition 2018-01 – Sterilization of health care products – Microbiological methods – Part 1: Determination of a population of microorganisms on product
- . ANSI/AAMI/ISO 11737-2:2009/(R) 2014 - Sterilization of medical devices -Microbiological methods – Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process
- . EN ISO 14155 Second edition 2011-02-01 – Clinical investigation of medical devices for human subjects – Good clinical practice
- . ISO 15223-1 Third Edition 2016-11-01 – Medical devices – Symbols to be used with medical device labels, labelling, and information to be supplied
- . ASTM F2052-15 - Standard Test Method for Measurement of Magnetically Induced Displacement Force on Medical Devices in the Magnetic Resonance Environment
- . ASTM F2182-11a – Standard Test Method for Measurement of Radio Frequency Induced Heating on a Near Passive Implants during Magnetic Resonance Imaging
- . ASTM F2213-17 – Standard Test Method for Measurement of Magnetically Induced Torque on Medical Devices in the Magnetic Resonance Environment
VIII. Clinical Data
The TULSA-PRO has been evaluated in prospective clinical trials, including the TACT Pivotal Study which was designed to determine the safety and effectiveness of the device according to the proposed intended use. Between September 2016 and February 2018, the TACT study enrolled 115 patients across the United States, Canada and Europe with biopsy-proven, organ-confined prostate cancer (67.0% and 33.0% of subjects had NCCN intermediate and low risk disease, respectively). All patients received primary treatment of whole-gland prostate ablation with sparing of the urethra and urinary sphincter. The median age of enrolled patients was 65
8
years, with targeted prostate volume of 40 cc and ultrasound treatment delivery time of 51 minutes. A median of 97.6% of the prescribed prostate volume was heated to an ablative thermal dose with spatial ablation precision of ±1.4 mm measured on MRI thermometry during treatment.
The primary efficacy endpoint of TACT was the proportion of patients achieving a post-treatment PSA reduction ≥ 75% of their pre-treatment baseline value. The primary safety endpoint was the frequency and severity of all adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Secondary endpoints included prostate volume reduction, proportion of patients with negative biopsy, patient reported changes in quality of life (erectile, urinary and bowel function), and evaluation of multiparametric prostate MRI. Primary and secondary endpoints were assessed at 12 months after TULSA-PRO treatment, with per-protocol follow-up continuing to 5 years.
The TULSA-PRO device used to collect clinical data was developed and manufactured in accordance with requirements of ISO 13485 compliant Quality Management System. The prospective clinical studies were conducted in accordance with 21 CFR 812 regulations.
Safety: Adverse Events
All Adverse Events (AE) were documented during the TACT study regardless of their attribution to the TULSA-PRO procedure. All AE's were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) developed by the NCI and were standardized to medical terminology using the Medical Dictionary for Regulatory Activities (MedDRA). Table 1 summarizes all AE observed during the TACT pivotal study through to the 12-month visit, regardless of severity or relation to the TULSA-PRO device or procedure. To 12 months, there was no rectal injury or fistula, and no severe urinary incontinence or erectile dysfunction. There were no Grade 4 or higher AE related or possibly related (attributable) to TULSA-PRO. There was one unrelated Grade 4 event of coronary artery disease resolved with a triple coronary artery bypass. There were 12 attributable Grade 3 AE in 9 patients (7.8%), all resolved by the 12 month follow-up. An additional 10 unrelated Grade 3 events occurred in 7 subjects, of which two were ongoing at 12 months: an upper GI bleed caused by esophageal adenocarcinoma which was resolving as of 12 months, and unrelated pelvic pain caused by a urinary stone which resolved after the 12 month visit.
The majority of attributable events were acute Grade 1 and 2 (occurring and resolving within 3 months of treatment), related to the genitourinary system.
9
Urethral stenosis occurred in 3 subjects (one Grade 2 and two Grade 3, all resolved). Urinary tract infections were common and resolved with oral antibiotics in nearly all affected patients. Urinary retention occurred in 9 attributable Grade 2 events (7% of patients) and 2 attributable Grade 3 events (1.7%), all resolved with medication and prolonged catheterization up to a maximum of less than 3 months. Attributable gastrointestinal AE were limited to acute Grade 1 events and 7 acute Grade 2 events: pain/discomfort (3.5% of subjects), nausea (1.7%), and constipation (0.9%), all of which resolved within one month and could potentially be attributed to anesthesia or GI anti-spasmodic medication.
Erectile dysfunction and urinary incontinence are common events after prostate therapies. Erectile dysfunction after TULSA-PRO in the TACT study was expected due to the whole-gland nature of the ablation. Of the 52 patients (45.2%) with some erectile dysfunction immediately after TULSA-PRO treatment, 49 (42.6%) were assessed by the study investigators as attributable to TULSA-PRO, of which 41 (35.7%) were ongoing at the 12-month follow-visit: 14 patients (12.2%) had mild erectile dysfunction (Grade 1, intervention not indicated), 27 patients (23.5%) had moderate erectile dysfunction (Grade 2, intervention such as medication indicated), and no patient (0%) had severe erectile dysfunction (Grade 3, intervention such as medication not helpful) or permanent disability.
Of the 28 patients (24.3%) with some urinary incontinence immediately after TULSA-PRO treatment, 26 (22.6%) were assessed by the study investigators as attributable to TULSA-PRO, of which 12 (10.4%) were ongoing at the 12-month follow-visit: 9 patients (7.8%) had mild urinary incontinence (Grade 1, occasional, pads not indicated), 3 patients (2.6%) had moderate urinary incontinence (Grade 2, spontaneous, pads indicated), and no patient (0%) had severe urinary incontinence (Grade 3, operative intervention indicated) or permanent disability.
Ongoing attributable moderate (Grade 2) AE at 12 months included ejaculatory disorder (retrograde ejaculation, 2.6% of subjects), weak urinary stream (2.6%), urinary tract infection (1.7%), and disrupted urethra (0.9%, identified on cystoscopy).
42 ( 36.5 %)
32 ( 27.8 %)
21 ( 18.3 %)
26 ( 22.6 %)
| Adverse Event (AE) | Any occurrence, regardless
of attribution
Subjects (%) (n=115) | Subset of AE attributable to
TULSA-PRO
Subjects (%) (n=115) |
|----------------------|------------------------------------------------------------------------|---------------------------------------------------------------------|
| Total | 109 ( 94.8 %) | 101 ( 87.8 %) |
| Erectile dysfunction | 52 ( 45.2 %) | 49 ( 42.6 %) |
48 ( 41.7 %)
42 ( 36.5 %)
29 ( 25.2 %)
28 ( 24.3 %)
Haematuria Urinary tract infection
Urinary incontinence
Dysuria
Table 1: Summary of all adverse events in TACT. Number of patients with AE, any
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Image /page/10/Picture/1 description: The image shows the logo for Profound Medical Inc. The word "PROFOUND" is in large, bold, blue letters. Below that, the word "MEDICAL" is in smaller, blue letters, and to the right of that, the letters "Inc." are in even smaller, blue letters. There is a blue line going through the letters "OU" in the word "PROFOUND", with a blue dot in the middle of the line.
| Adverse Event (AE) | Any occurrence, regardless
of attribution
Subjects (%) (n=115) | Subset of AE attributable to
TULSA-PRO
Subjects (%) (n=115) |
|----------------------------------------------------|------------------------------------------------------------------------|---------------------------------------------------------------------|
| Pain/discomfort
(pelvic/genital/treatment area) | 27 (23.5%) | 25 (21.7%) |
| Oedema (testicular, scrotal, penile) | 27 (23.5%) | 24 (20.9%) |
| Urinary urgency | 26 (22.6%) | 25 (21.7%) |
| Catheter site pain/inflammation | 20 (17.4%) | 7 (6.1%) |
| Pain/discomfort (abdominal/anorectal) | 17 (14.8%) | 14 (12.2%) |
| Urinary frequency | 16 (13.9%) | 16 (13.9%) |
| Bladder spasm | 14 (12.2%) | 12 (10.4%) |
| Ejaculation disorder | 14 (12.2%) | 14 (12.2%) |
| Non-descriptive LUTS | 14 (12.2%) | 10 (8.7%) |
| Urinary retention | 13 (11.3%) | 10 (8.7%) |
| Urethral bleeding | 13 (11.3%) | 13 (11.3%) |
| Pain/discomfort (hip/back) | 12 (10.4%) | 9 (7.8%) |
| Urethral discharge | 11 (9.6%) | 11 (9.6%) |
| Weak urinary stream | 11 (9.6%) | 11 (9.6%) |
| Pain/discomfort (bladder/urinary tract) | 10 (8.7%) | 9 (7.8%) |
| Fatigue | 9 (7.8%) | 3 (2.6%) |
| Hypotension | 8 (7%) | |
| Nausea | 8 (7%) | 2 (1.7%) |
| Epididymitis | 7 (6.1%) | 7 (6.1%) |
| Headache | 7 (6.1%) | 2 (1.7%) |
| Debris in urine | 5 (4.3%) | 5 (4.3%) |
| Orchitis | 5 (4.3%) | 2 (1.7%) |
| Constipation | 4 (3.5%) | 2 (1.7%) |
| Dyspepsia | 4 (3.5%) | |
| Fever | 4 (3.5%) | 3 (2.6%) |
| Hypertension | 4 (3.5%) | |
| Nocturia | 4 (3.5%) | 3 (2.6%) |
| Procedural hypotension | 4 (3.5%) | |
| Libido decreased | 4 (3.5%) | |
| Inguinal hernia | 3 (2.6%) | |
| Urethral stenosis | 3 (2.6%) | 3 (2.6%) |
| Calculus urinary | 2 (1.7%) | 1 (0.9%) |
| Hydronephrosis | 2 (1.7%) | 1 (0.9%) |
| Anaemia | 1 (0.9%) | |
| Syncope | 1 (0.9%) | |
| Upper gastrointestinal haemorrhage | 1 (0.9%) | |
| Urinoma | 1 (0.9%) | 1 (0.9%) |
| Urosepsis | 1 (0.9%) | |
| Deep vein thrombosis | 1 (0.9%) | 1 (0.9%) |
| Diverticulitis | 1 (0.9%) | |
| Ileus | 1 (0.9%) | |
| Other* | 95 (82.6%) | 41 (35.7%) |
- Includes all non-serious Grade ≤ 2 events with occurrence in