(197 days)
The leva Pelvic Health System is intended for:
- Strengthening of the pelvic floor muscles;
- Rehabilitation and training of weak pelvic floor muscles for the treatment of stress, mixed and mild to moderate urgency urinary incontinence (including overactive bladder) in women;
- Rehabilitation and training of weak pelvic for the first-line treatment of chronic fecal incontinence (>3month uncontrolled passage of feces) in women.
This device interacts with the user via smart phone technology.
The leva Pelvic Health System ("leva PHS" or "leva System") is a prescription intra-vaginal device designed to allow the user to rehabilitate and strengthen their pelvic floor muscles ("PFM") as well as allow them to monitor their progress during pelvic floor muscle training ("PFMT"). The leva system is designed to wirelessly facilitate PFMT in women and to transmit real-time performance data through a dedicated mobile application that has been downloaded onto the patient's mobile device. The leva system is designed to be used vaginally and is intended to be used repeatedly by a single patient.
The provided text describes clinical studies for the Renovia leva Pelvic Health System, but it does not specifically mention acceptance criteria or a study designed to universally "prove the device meets acceptance criteria" for a diagnostic or AI-driven system.
Instead, the document details two clinical studies (REN-17 and REN-19) that support the expanded indications for use of the device, particularly for fecal incontinence. These studies serve to demonstrate the device's safety and effectiveness for its intended use, thereby establishing substantial equivalence to a predicate device.
Here's an analysis based on the information provided, tailored to address the points in the prompt, with a strong caveat that the traditional "acceptance criteria" and "study proving it meets acceptance criteria" framework, as typically applied to diagnostic AI, is not explicitly present here. The studies focus on clinical effectiveness and safety rather than specific technical performance metrics of an AI algorithm.
1. A table of acceptance criteria and the reported device performance
The document does not present explicit "acceptance criteria" in the format of a diagnostic performance target (e.g., sensitivity > X%, specificity > Y%). Instead, the studies aim to demonstrate clinical improvement and non-inferiority/superiority in patient-reported outcomes for fecal incontinence. The performance is measured by changes in clinical scores.
| Acceptance Criteria (Implied Clinical Effectiveness) | Reported Device Performance (REN-17) | Reported Device Performance (REN-19 Subset Analysis - leva-02 arm vs. Kegel arm) |
|---|---|---|
| REN-17: Statistical significance in primary effectiveness endpoint (Change in St. Mark's Score) | Mean St. Mark's score improved from 14.6 at baseline to 11.6 at 10 weeks (p=0.008). | N/A (REN-17 was a single-arm study) |
| REN-19 (CRADI-8): Statistically significant improvement in overall CRADI-8 score. | N/A | Both arms demonstrated statistically significant improvement for CRADI-8 from baseline to 8 weeks and 6 months. |
| REN-19 (CRADI-8): Improvement meets minimum clinical important difference (MCID) for CRADI-8 (-4.68). | N/A | Both arms met MCID at 8 weeks. |
| REN-19 (CRADI-8): Statistically superior improvement in CRADI-8 at 6 months compared to control. | N/A | leva-02 arm demonstrated statistically significant greater improvement compared to Kegel arm at 6 months (p=0.01). |
| REN-19 (CRADI-8 Q4 - Loose Stool): Statistically superior improvement in control of loose stool at 6 months. | N/A | leva-02 arm demonstrated statistically significant greater improvement compared to Kegel arm at 6 months (p=0.04). |
| REN-19 (CRAIQ-7): Statistically significant improvement in overall CRAIQ-7 score. | N/A | Both arms demonstrated statistically significant improvement for CRAIQ-7 from baseline to 8 weeks. |
| REN-19 (CRAIQ-7): Improvement meets minimum clinical important difference (MCID) for CRAIQ-7 (-8.01). | N/A | Only leva-02 arm met MCID at 8 weeks. |
| REN-19 (CRAIQ-7): Statistically superior improvement in CRAIQ-7 at 6 months compared to control. | N/A | leva-02 arm demonstrated statistically significant greater improvement compared to Kegel arm at 6 months (p=0.02). |
| Safety: Low incidence of serious adverse events; device-related adverse events are non-serious. | Three possibly device-related AEs (two UTIs, one yeast infection), none serious. Participants continued study. | Control group: two UTIs (not intervention related). leva-02 group: one AE (vaginal spotting), possibly intervention related, resolved. None serious. |
2. Sample size used for the test set and the data provenance
- REN-17 (Single-arm study for primary effectiveness):
- Test set (Effectiveness Analysis): 26 participants
- Test set (Safety Analysis): 27 participants
- Data provenance: United States only, prospective.
- REN-19 (RCT Subset Analysis for fecal incontinence symptoms):
- Test set (Effectiveness/Safety Analysis): 92 participants (44 in leva-02 arm, 48 in control arm).
- Data provenance: United States only, prospective (subset of a larger RCT).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the document. For this type of device (pelvic floor muscle training biofeedback), the "ground truth" is typically established by patient-reported outcomes (like St. Mark's Score, CRADI-8, CRAIQ-7), which are subjective measures of symptoms and quality of life, rather than objective assessments requiring expert interpretation of raw data. The device provides biofeedback, and the clinical studies assess the impact of that biofeedback on patient outcomes.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not provided and is generally not applicable to studies relying primarily on validated, self-reported patient questionnaires for primary endpoints. The CRADI-8 and CRAIQ-7 are validated patient-reported symptom scales. St. Mark's Score is also a validated questionnaire completed by the patient, though occasionally a clinician might administer it.
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
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The leva Pelvic Health System is a biofeedback device for pelvic floor muscle training, not an AI-driven diagnostic imaging or interpretation tool that assists human readers. The clinical studies compare its effectiveness in improving clinical outcomes (like fecal incontinence symptoms and quality of life) against standard care (unassisted Kegel exercises) or against baseline, but not in the context of an AI-assisted diagnostic workflow involving human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This question is not applicable in the traditional sense for this device. The device itself is a "human-in-the-loop" system by design, providing real-time biofeedback to the user during exercises. Its "performance" is measured by its impact on clinical outcomes when used by patients, not by an algorithm's isolated diagnostic accuracy. The text states that the device transmits biofeedback to an app, and the previous 510(k) comparison indicates the "Principle of Operation" is "Provides indication of relative position of pelvic floor muscle contraction using accelerometers." This refers to its sensing capabilities. The clinical studies assess the overall effect of using this system (device + app + patient interaction) on health outcomes.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for effectiveness was established using patient-reported outcomes data from validated questionnaires:
- St. Mark's Score (Vaizey) for fecal incontinence severity (REN-17).
- FIQoL (Fecal Incontinence Quality of Life) for different aspects of quality of life (REN-17).
- CRADI-8 (Colorectal-Anal Distress Inventory, Short Form) for fecal incontinence symptoms (REN-19 subset).
- CRAIQ-7 (Colorectal-Anal Impact Questionnaire Short Form) for condition-specific quality of life (REN-19 subset).
Fecal incontinence diagnosis itself was based on pre-defined screening criteria reported by participants.
8. The sample size for the training set
The document does not specify a training set sample size because the reported studies (REN-17 and REN-19) are clinical trials designed to assess the device's efficacy and safety in human subjects, not to train a machine learning model. While the device certainly has internal software and algorithms that might have been developed using some data, these clinical studies are distinct from the paradigm of "AI training sets."
9. How the ground truth for the training set was established
As there is no explicit "training set" described in the context of AI model development, this question is not directly applicable. If one were to consider the broader development cycle of the device, the "ground truth" for the device's biofeedback mechanism (e.g., accurately reflecting pelvic floor muscle contraction) would have been established through engineering validation and verification testing, likely comparing accelerometer data to known movements or potentially against electromyography (EMG) or pressure-based perineometry, but this is not detailed in the provided clinical study summaries. The clinical studies use actual patient outcomes as their measure of effectiveness.
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June 30, 2022
Renovia Inc. % Jacqueline Schmainda Regulatory Consultant Bold Type 2100 N Alafaya Trail Orlando, FL 32826
Re: K213913
Trade/Device Name: leva Pelvic Health System Regulation Number: 21 CFR 884.1425 Regulation Name: Perineometer Regulatory Class: Class II Product Code: HIR Dated: June 1, 2022 Received: June 2, 2022
Dear Jacqueline Schmainda:
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. You must comply with all the Act's
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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 (OS) 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,
for
Je Hi An, Ph.D. Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant 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) K213913
Device Name leva Pelvic Health System
Indications for Use (Describe)
The leva Pelvic Health System is intended for:
-
Strengthening of the pelvic floor muscles;
-
Rehabilitation and training of weak pelvic floor muscles for the treatment of stress, mixed and mild to moderate urgency urinary incontinence (including overactive bladder) in women;
-
Rehabilitation and training of weak pelvic for the first-line treatment of chronic fecal incontinence (>3month uncontrolled passage of feces) in women.
This device interacts with the user via smart phone technology.
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/2 description: The image shows the word "Renovia" in a stylized font. The word is in a purple color. Above the right side of the word are three curved lines.
This 510(k) Summary has been prepared in accordance with 21 CFR 807.92.
1. Submitter
| Name and Address: | Renovia Inc.263 Summer StreetBoston, MA 02210 |
|---|---|
| Primary Contact: | Jacqueline SchmaindaRegulatory Consultant on behalf of RenoviaRenovia Inc.263 Summer StreetBoston, MA 02210Phone: 763-269-2069Email: jackie@boldtype.com |
| Date Prepared: | June 27, 2022 |
2. Device Information
| Trade Name: | leva® Pelvic Health System |
|---|---|
| Model: | leva-02 |
| Common Name: | Perineometer |
| Product Code: | HIR |
| Regulatory Class | Class II |
| Regulation Number: | 21 CFR 884.1425 |
| FDA Panel: | Obstetrics / Gynecology |
3. Predicate Information
| 510(k) Number | Trade Name | Applicant |
|---|---|---|
| K212495 | leva Pelvic Health System | Renovia Inc. |
4. Device Description
The leva Pelvic Health System ("leva PHS" or "leva System") is a prescription intra-vaginal device designed to allow the user to rehabilitate and strengthen their pelvic floor muscles ("PFM") as well as allow them to monitor their progress during pelvic floor muscle training ("PFMT"). The leva system is designed to wirelessly facilitate PFMT in women and to transmit real-time performance data through a dedicated mobile application that has been downloaded onto the patient's mobile device. The leva system is designed to be used vaginally and is intended to be used repeatedly by a single patient.
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5. Indications for Use
The /eva Pelvic Health System is intended for:
-
- Strengthening of the pelvic floor muscles;
- Rehabilitation and training of weak pelvic floor muscles for the treatment of stress, mixed and mild 2) to moderate urgency urinary incontinence (including overactive bladder) in women;
-
- Rehabilitation and training of weak pelvic floor muscles for the first-line treatment of chronic fecal incontinence (≥3-month uncontrolled passage of feces) in women.
This device interacts with the user via smart phone technology.
6. Comparison of Technological Characteristics
The following table provides a comparison of the leva Pelvic Health System to the predicate device.
| Characteristic | Subject Device | Predicate Device |
|---|---|---|
| leva PHS | leva PHS | |
| This Submission | K212495 | |
| Regulatory Information | ||
| Brand Name | leva Pelvic Health System | leva Pelvic Health System |
| Manufacturer | Renovia Inc. | Renovia Inc. |
| Model Number | leva-02 | leva-02 |
| Common or UsualName | Perineometer | Perineometer |
| Regulation | 21 CFR 884.1425 | 21 CFR 884.1425 |
| Class | Class II | Class II |
| Product Code | HIR | HIR |
| Intended Use / Indications for Use | ||
| Intended Use | Strengthen pelvic floor muscles for thetreatment of urinary incontinence and fecalincontinence | Strengthen pelvic floor muscles for thetreatment of urinary incontinence |
| Indications for UseStatement | The leva Pelvic Health System is intended for:1) Strengthening of the pelvic floor muscles;2) Rehabilitation and training of weak pelvicfloor muscles for the treatment of stress,mixed and mild to moderate urgencyurinary incontinence (including overactivebladder) in women;3) Rehabilitation and training of weak pelvicfloor muscles for the first-line treatment ofchronic fecal incontinence (>3-monthuncontrolled passage of feces) in women.This device interacts with the user via smartphone technology. | The leva Pelvic Health System is intended for:1) Strengthening of the pelvic floor muscles;2) Rehabilitation and training of weak pelvicfloor muscles for the treatment of stress,mixed and mild to moderate urgencyurinary incontinence (including overactivebladder) in women.This device interacts with the user via smartphone technology. |
| Subject Device | Predicate Device | |
| Characteristic | leva PHS | leva PHS |
| This Submission | K212495 | |
| Technological Characteristics | ||
| Principle of Operation | Provides indication of relative position ofpelvic floor muscle contraction usingaccelerometers | Provides indication of relative position ofpelvic floor muscle contraction usingaccelerometers |
| Mechanism of Action | Lift and Squeeze for pelvic floor musclestrengthening. The leva sensor hardware(probe) transmits biofeedback to leva Appwhich is displayed to user. | Lift and Squeeze for pelvic floor musclestrengthening. The leva sensor hardware(probe) transmits biofeedback to leva Appwhich is displayed to user. |
| Electrical Stimulation | No | No |
| Parameter | Relative position of device | Relative position of device |
| Anatomical Use | Vaginal only | Vaginal only |
| Single Patient Device | Yes | Yes |
| Reusable | Yes | Yes |
| Sterility | Non-sterile, clean | Non-sterile, clean |
| Information Display | Graphical and numeric based on impliedbending, anatomical overlay | Graphical and numeric based on impliedbending, anatomical overlay |
| Patient Contact(Contact Duration) | • Probe: Direct (<24 hours)• Probe Battery Pack: Direct (<24 hours)• Vaginal Probe Hub: Indirect (Incidental)• Battery Pack Cap: Indirect (Incidental) | • Probe: Direct (<24 hours)• Probe Battery Pack: Direct (<24 hours)• Vaginal Probe Hub: Indirect (Incidental)• Battery Pack Cap: Indirect (Incidental) |
| Patient ContactMaterials | • Probe: Thermoplastic Elastomer• Probe Hub: Polypropylene• Battery Pack: Hard Plastic | • Probe: Thermoplastic Elastomer• Probe Hub: Polypropylene• Battery Pack: Hard Plastic |
| Probe Shape | • Oval | • Oval |
| Storage | • Storage case provided with device | • Storage case provided with device |
| Primary SystemElements | • Wireless Vaginal Probe• User Interface Device (i.e., smartphone,tablet)• Mobile Application | • Wireless Vaginal Probe• User Interface Device (i.e., smartphone,tablet)• Mobile Application |
| Power Source | • Device: Non-rechargeable silver oxide 1.5VCoin Cell• Storage Case: Non-rechargeable CR2032 3VCoin Cell | • Device: Non-rechargeable silver oxide 1.5VCoin Cell• Storage Case: Non-rechargeable CR2032 3VCoin Cell |
| Wireless Technology | • Bluetooth Low Energy (BLE) | • Bluetooth Low Energy (BLE) |
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Renovía
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Summary of Nonclinical Testing and Risk Analysis 7.
Nonclinical testing of the leva Pelvic Health System was not required for the indications for use statement. Minor modifications made to the device since last clearance were summarized in this submission and included reference to design verification and/or design validation activities and risk analyses, where applicable.
A. Hardware Changes
There were no hardware changes made to the leva Pelvic Health System to support the expanded indications for use statement.
B. Software Changes
No software changes were made to the medical device functionality of the leva Pelvic Health System. More specifically, there were no changes to the mobile application which modified how the user interacts with the device. All software modifications were reviewed and evaluated following the software life cycle processes for medical device software as defined by IEC 62304. The only changes to the software of the leva Pelvic Health System relate to non-medical device functionality (aka "other functionality") under FDA's guidance on "Multiple Function Device Products: Policy and Considerations" (2020). Software modifications related to "other functionality" included the addition of educational information regarding fecal incontinence to the mobile application. Regression analyses were conducted to determine the scope of software testing to be reexecuted related to these modifications and the test results supported the implementation of updated software version.
8. Clinical Testing
The mechanism of action of the leva Pelvic Health System has been the subject of multiple published, peerreviewed clinical trials studying its efficacy, including the two studies outlined below. The data from the referenced clinical studies supports the leva Pelvic Health System can serve as a safe and to provide feedback when performing pelvic floor training in the treatment of fecal incontinence. In all studies, the leva device was used vaginally to perform the same type of pelvic floor muscle training.
A. REN-17 Study (NCT04027335):
The REN-17 Study was a ten (10) week, single-arm, open-label study involving thirty-one (31) participants who engaged in pelvic floor muscle training (PFMT) using the leva Pelvic Health System (leva-01). Subject selection was based on meeting pre-defined screening criteria, including fecal incontinence ("FI") defined as any uncontrolled loss of liquid or solid fecal material that occurs at least monthly over the last three (3) months and is bothersome enough to desire treatment.
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| REN-17 – Summary | |
|---|---|
| Level of Evidence: | Single-arm study with Performance Goals |
| Location of Study: | United States only |
| Primary Effectiveness Endpoint: | Change in St. Mark's Score |
| Was the study primary endpoint met? | Yes, participants reported a mean St. Mark's Score of 14.6 at baselinewhich improved to 11.6 at ten weeks (p=0.0047). The sample sizeneeded to avoid a type β error was met. |
| Adverse events and complications: | There were three adverse events reported as possibly device related– two urinary tract infections and one yeast infection. None of theseadverse events were considered serious and the participantscontinued to participate in the study through the ten-week endpoint. |
| REN-17 - Patient Accountability | |||||
|---|---|---|---|---|---|
| Stage | Treatment Group (Single-Arm) | ||||
| Enrollment | 31 participants | ||||
| Treatment | 27 participants | ||||
| Primary Effectiveness Endpoint Analysis | 26 participants | ||||
| Primary Safety Endpoint Analysis | 27 participants |
| REN-17 – Study Results | ||||
|---|---|---|---|---|
| Endpoint | n | Baseline | Week 10 | Wilcoxon signed rank test |
| St. Mark's Score (Vaizey) | 26 | $14.6 \pm 4.37$ | $11.6 \pm 5.12$ | 0.008 |
| FIQoL - Lifestyle | 26 | $2.7 \pm 0.85$ | $3.1 \pm 0.84$ | <0.001 |
| FIQoL - Coping | 26 | $2.2 \pm 0.73$ | $2.5 \pm 0.81$ | <0.001 |
| FIQoL - Depression | 26 | $3.0 \pm 0.68$ | $3.2 \pm 0.70$ | <0.001 |
| FIQoL - Embarrassment | 26 | $2.1 \pm 0.84$ | $2.3 \pm 0.88$ | 0.06 |
| Bowel Diary | 21 | $8.4 \pm 8.73$ | $4.8 \pm 3.79$ | 0.052 |
*Bold text identifies statistical significance <0.05.
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B. REN-19 (NCT04508153):
The REN-19 Study was an eight (8) week, randomized controlled trial ("RCT") that included two hundred ninety-nine (299) women with stress and stress-dominant mixed urinary incontinence ("UI") that included completion of pelvic floor muscle training ("PFMT") for all participants (control and treatment groups) and evaluated the participants as follows:
- o Control Group: Performed PFMT after receiving a standardized written and verbal instructions but without the aid of any device, effectively performing what are commonly called Kegel exercises.
- Treatment Group: Performed PFMT using the leva Pelvic Health System (leva-02). O
While the primary endpoints of the Ren-19 RCT involved PFMT for the treatment of stressdominant mixed UI, the trial also included several secondary endpoints including the Colorectal-Anal Distress Inventory, Short Form (the "CRADI-8"). The CRADI-8 is a validated patient-reported symptom scale, validated, in part, based on the outcomes of bowel diaries.
Renovia completed a subset analysis of participants from the Ren-19 RCT who indicated they had fecal incontinence ("FI") symptoms. Participants included in the subset analysis met all of the inclusion criteria for the larger study and, in addition, indicated they "usually lose stool beyond their control" for well-formed or loose stool, with a bother of at least "somewhat" in their responses to the CRADI-8. Based on the same modified intent to treat plan executed for the larger study, a subset of 92 participants was identified as meeting this additional inclusion criteria.
The purpose of the subset analysis was to evaluate symptom improvement of the 92 participants with Fl over the study period within their assigned treatment group and to compare the results between the 48 participants in the control group (at-home PFMT without leva-02) and the 44 participants in the intervention group (at-home PFMT with leva-02). By focusing on participants with FI, it is possible to better assess the impact of the control treatment vs. the intervention treatment on FI symptoms.
| REN-19 Subset Analysis – Summary | |
|---|---|
| Level of Evidence: | Randomized, multi-arm, unblinded study with an active control |
| Location of Study: | United States only |
| Effectiveness Endpoints: | 1) Change in participants' symptoms using the Colorectal-Anal DistressInventory, Short Form (the “CRADI-8”)2) Change in participants' condition-specific quality of life assessment usingthe Colorectal-Anal Impact Questionnaire Short Form (the “CRAIQ-7”) |
| REN-19 Subset Analysis - Patient Accountability | ||
|---|---|---|
| Stage | Treatment Group ( leva -02) | Control Group (Active) |
| Treatment | 44 participants | 48 participants |
| Primary Effectiveness Endpoint Analysis | 44 participants | 48 participants |
| Primary Safety Endpoint Analysis | 44 participants | 48 participants |
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Safety:
There were no treatment-related severe adverse events in either arm of the Ren-19 Study. Looking at only those 92 participants within the Fl subset analysis, there were two (2) urinary tract infections in the control (Kegel) group, neither of which were deemed to be intervention related, and none in the intervention (leva-02) group. There was one (1) adverse event, vaginal spotting, in one subject which was reported as "possibly" intervention related occurring in the intervention (leva-02) arm. This resolved before the end of the study and the participant resumed use of the device without complication through the study endpoint at 8 weeks.
Endpoints:
The Ren-19 subset analysis compared participants' overall CRADI-8 scores and the two individual questions within the CRADI-8 specifically addressing Fl, and participants' condition-specific quality of life assessment using the Colorectal-Anal Impact Questionnaire Short Form (the "CRAIQ-7") – each at baseline, 8-weeks, and 6-months.
The results of the FI subset analysis demonstrate that FI symptom improvement of those in the leva-02 arm was statistically superior to that of participants in the Kegel arm, as summarized in the Results table below.
CRADI-8 Results:
On the CRADI-8, both the Kegel arm and the leva-02 arm demonstrated statistically significant improvement that met the minimum clinical important difference ("MCID") (-4.68) for the CRADI-8 at 8 weeks. Jelovsek, Chen et. al. found in their 2014 publication, Minimum Important Differences for Scales Assessing Symptom Severity and Quality of Life in Patients with Fecal Incontinence (available at doi: 10.1097/SPV.00000000000000078), that the MCID for the CRADI-8 is a reduction of 4.68.
While the improvement in the leva-02 arm was greater, there was not a statistically significant difference between the groups at 8 weeks (P=.54). However, the CRADI-8 symptom improvement of the leva-02 group was statistically significantly greater at 6 months. This difference at 6 months was driven by the fact that the CRADI-8 results of participants in the Kegel arm did not continue to improve between 8 weeks and 6 months. In the leva-02 arm, however, the CRADI-8 results continued to improve between 8 weeks and 6 months.
This result of stronger continued improvement in Fl symptoms through 6 months within the leva-02 arm is also evident in the results of the questions 3 and 4 of CRADI-8, which are the two questions within the survey that specifically address loss of stool.2 As shown in Table 4 below, the symptom improvement specific to the control of loose stool was statistically superior within the leva-02 arm at 6 months.
CRAIQ-7 Results:
In the CRAIQ-7 assessing participants' condition-specific quality of life, both the Kegel arm and the leva-02 arm demonstrated statistically significant improvement at 8 weeks. However, only participants in the leva-02 arm reported results that met the MCID (-8.01) for the CRAIQ-7 at 8 weeks (see Jelovsek, Chen et. dl. for MCID on CRAIQ-7).
While the CRAIQ-7 improvement in the leva-02 arm was greater, there was not a statistically significant difference between the groups at 8 weeks (P=.39). However, the CRAIQ-7 improvement of the leva-02 group demonstrated improvement that was statistically significantly greater at 6 months (p=0.02). This difference at 6 months was driven by the fact that the CRAIQ-7 results of participants in the Kegel arm did not continue
1 Question 3 of the CRADI-8 asks: Do you usually lose stool beyond your control if your stool is well formed? Question 4 of the CRADI-8 asks: Do you usually lose stool beyond your control if your stool is loose?
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to improve between 8 weeks and 6 months. In the leva-02 arm, however, the CRAIQ-7 results continued to improve between 8 weeks and 6 months.
| REN-19 Subset Analysis – Results | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 8 weeks | Baseline to 6 months | ||||||||||
| Baseline | 8Weeks | Abs MeanDifference | Pairedt-test | Studentst-test | Baseline | 6Months | Abs MeanDifference | Pairedt-test | Studentst-test | ||
| CRADI-8 (full survey) | |||||||||||
| Kegel arm | 40.9(±19.9) | 29.2(±22.4) | -5.3(±14.3) | <0.001 | 40.9(±19.9) | 29.6(±20.2) | -6.8(±15.0) | <0.001 | 0.01 | ||
| leva-02 arm | 37.7(±20.7) | 27.8(±20.6) | -3.0(±15.0) | <0.001 | 0.54 | 37.7(±20.7) | 17.2(±19.4) | -8.6(±13.8) | <0.001 | ||
| CRADI-8: Question 3 (Loss of Well-Formed Stool) | |||||||||||
| Kegel arm | 0.9(±1.6) | 0.7(±1.4) | -0.1(±1.0) | 0.3523 | 0.53 | 0.9(±1.6) | 0.5(±1.3) | -0.1(±1.1) | 0.1914 | 0.64 | |
| leva-02 arm | 0.6(±1.3) | 0.5(±1.3) | 0.1(±0.7) | 0.7656 | 0.6(±1.3) | 0.2(±0.8) | -0.1(±0.7) | ||||
| CRADI-8: Question 4 (Loss of Loose Stool) | |||||||||||
| Kegel arm | 3.2(±1.0) | 2.0(±1.7) | -0.2(±1.4) | <0.001 | 0.45 | 3.2(±1.0) | 2.0(±1.9) | -0.2(±1.4) | <0.001 | 0.04 | |
| leva-02 arm | 3.09(±1.1) | 1.6(±1.6) | 0.2(±1.5) | <0.001 | 3.09(±1.1) | 1.0(±1.6) | -0.4(±1.5) | <0.001 | |||
| CRAIQ-7 | |||||||||||
| Kegel arm | 23.5(±27.4) | 16.7(±21.7) | -4.3(±14.6) | 0.02 | 23.5(±27.4) | 17.5(±24.7) | -3.8(±13.1) | 0.1175 | |||
| leva-02 arm | 23.5(±25.0) | 12.3(±17.0) | -5.0(±13.7) | <0.001 | 0.39 | 23.5(±25.0) | 10.4(±18.3) | -4.2(±15.5) | <0.001 | 0.02 |
*Bold text identifies statistical significance <0.05.
9. Risk Review
In support of the expanded indications for use statement, a risk review was conducted for the use of the leva Pelvic Health System as a first-line treatment of chronic fecal incontinence in women. The risk review confirmed that there were no new or increased risks associated with the device which would raise new questions of safety or effectiveness.
10. Conclusion
Renovia has demonstrated that the leva Pelvic Health System is as safe and effective as the predicate device for its intended use and substantially equivalent to the predicate device.
§ 884.1425 Perineometer.
(a)
Identification. A perineometer is a device consisting of a fluid-filled sack for intravaginal use that is attached to an external manometer. The devices measure the strength of the perineal muscles by offering resistence to a patient's voluntary contractions of these muscles and is used to diagnose and to correct, through exercise, uninary incontinence or sexual dysfunction.(b)
Classification. Class II (performance standards).