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U.S. Department of Health and Human Services

Post-Approval Studies (PAS) Database

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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5 year registry - ROSE


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General
Study Status Completed
Application Number P040050 / PAS001
Date Current Protocol Accepted 10/30/2006
Study Name 5 year registry - ROSE
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source Sponsor Registry
Comparison Group No Control
Analysis Type Descriptive
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description The Real-Time Observation of Safety and Effectiveness (ROSE) study is a non-randomized, prospective, multi-center, registry of Macroplastique safety and effectiveness.
Study Population Description The study population consists of women at least 18 years of age diagnosed with stress urinary incontinence primarily due to intrinsic sphincter deficiency who are candidates for treatment with the device according to the approved labeling,. This device is indicated for transurethral injection in the treatment of adult women diagnosed with stress urinary incontinence primarily due to intrinsic sphincter deficiency.
Sample Size 275 enrolled patients and maximum of 20 sites
Data Collection The primary endpoints are additional or alternative surgical treatment over a 5-year period and incidence of genitourinary and treatment-related adverse events. Other endpoints collected are: change in Incontinence Quality of Life questionnaire, change in Stamey grade, and change in number of incontinence episodes per day from baseline to 5 years as well as subject perception of treatment success.
Follow-up Visits and Length of Follow-up Subjects are followed for 5 years following initial treatment with Macroplastique or until alternative treatment for stress urinary incontinence.
Interim or Final Data Summary
Actual Number of Patients Enrolled Two hundred and seventy-six (276)
Actual Number of Sites Enrolled Twenty (20)
Patient Follow-up Rate 86% (148/172). This rate of follow-up is arrived at by excluding 93 patients who discontinued, 11 patients who died, 20 patients who were lost to follow-up and 4 patients who missed the 5 year follow-up visit.
Final Safety Findings The primary safety objective was to describe the incidence of genitourinary and treatment related adverse events, including transient symptoms associated with the injection procedure. No formal hypothesis testing was conducted.
A total of 343 genitourinary adverse events (AEs) occurred in 276 study subjects. The highest rate of reported non-serious AEs is Urinary Tract Infection (UTI) at 59.8%. The highest rate of related non-serious AEs is Urinary Retention occurring in 6.2% subjects and is a known side effect of the treatment. Other related reported treatment events are Post Procedure Catheterization (2.9%), Hematuria (2.2%).
Incomplete Bladder Emptying (1.8%), Pain at Implantation Site (1.4%), and Hesitance (1.1%). The adverse event of Erosion has been reported five (5) times in the study,, three (3) urethral (1.09%) and one (1) vaginal (0.36%) were deemed related to the device and one (1) urethral (0.36%) was assessed to be unrelated. The event of worsening of urgency/frequency symptoms was noted 3 times of which one was assessed to be related to the procedure. Additionally, device protrusion, device migration, vaginal mass, and an incidence of a benign neoplasm were observed which were reported as “other” urogenital adverse events.
The protocol specified that subjects exiting the study prior to five (5) years of follow-up (e.g., lost to follow-up, withdrawals other than to seek other treatment, death) with no additional treatment reported during follow-up will be censored at the time of study exit or at the last documented follow-up visit where the endpoint is known. Therefore, the reported rates only reflect best case imputation and do not reflect the observed and worst case imputation.
Final Effect Findings The primary effectiveness objective was to describe the incidence of additional or alternative treatment for stress urinary incontinence (SUI) primarily due to intrinsic sphincteric deficiency (ISD) following up to two Macroplastique treatments in order to evaluate the durability of the treatment effect over a 5-year period. No formal hypothesis testing was conducted.
A Kaplan Meier analyses showed the percentage of patients seeking alternate treatment decreased during the 5-years at 12-month interval measuring points. The rates were 7% in the first year (93% event free),6.5% in the second (86.4% event free), 4.2% in third 82.2% event free), 3.2% in the fourth (79.0% event free), and 2.5% in the fifth year after initial treatment (76.5% event free).
The protocol specified that subjects exiting the study prior to five (5) years of follow-up (e.g., lost to follow-up, withdrawals other than to seek other treatment, death) with no additional treatment reported during follow-up will be censored at the time of study exit or at the last documented follow-up visit where the endpoint is known. Therefore, the reported rates above show the percentage of patients seeking alternate treatment where subjects are censored and excluded from the denominators in the calculation. A total of 143 subjects were censored at 60 months.
The observation proportion of patients seeking alternative treatments, based on the available data at 60 months, was 60/207 (29.0%) and the estimated proportion based on the ITT population was 129/276 (46.7%) when subjects with missing data were treated as failures, constituting a worst-case scenario.
The combined total volume of Macroplastique injected from the first and second treatment (if needed) is correlated with failure, with higher volumes more likely to experience failure.

Study Strengths & Weaknesses Some study limitations include the single arm design of the study, no pre-specified formal hypothesis, no clearly defined method of outcome evaluation, no adjudication of adverse events, and too many subjects with missing data. The high rate of follow up is because of excluding 93 patients who discontinued, 11 patients who died, 20 patients who were lost to follow-up and 4 patients who missed the 5 year follow-up visit. This type of censoring, i.e., patients who counted as failures vs. patients who discontinued for reasons other than seeking alternative treatments, was stated in the protocol. Additionally, due to the missing numbers at follow up, some emerging AEs like urethral/vaginal erosion were not adequately evaluated.
Recommendations for Labeling Changes Recommend update to the labeling to reflect safety and effectiveness results from the study. Specifically, the labeling should address the following:

1. The revised labeling should adequately reflect the observed adverse events (AEs) based on the safety findings of the study including, but not limited to, urinary tract infection (UTI), urinary retention, device protrusion, device migration, vaginal mass, and benign neoplasm.

2. Based on the final results of the PAS, there is a risk of vaginal/urethral erosion with use of the device, which is not adequately reflected in the labeling. The revised labeling should adequately reflect the risk of erosion, including a reporting of the erosion rate, the required treatment (e.g., methods of surgical resection) that was observed in the study, and information regarding potential symptoms related to possible erosion and surgical resection instructions.

3. The revised labeling should include the primary effectiveness endpoint results based on the observation proportion based on the available data at 60 months and the estimated proportion based on the intent-to-treat (ITT) population to adequately report the durability and long term effectiveness of the subject device.


5 year registry - ROSE Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
6 month report 04/30/2007 04/26/2007 On Time
1 year registry report 10/30/2007 11/01/2007 Overdue/Received
18 month registry report 04/29/2008 04/29/2008 On Time
2 year registry report 10/29/2008 10/29/2008 On Time
3 year registry report 10/29/2009 10/29/2009 On Time
4 year registry report 10/29/2010 10/29/2010 On Time
5 year registry report 10/29/2011 10/28/2011 On Time
6 year registry report 10/28/2012 10/26/2012 On Time
7 year report 10/28/2013 10/25/2013 On Time
8 year report 10/28/2014 10/24/2014 On Time
9 year report 10/28/2015 10/15/2015 On Time
10 year report 10/28/2016 10/20/2016 On Time
11 year report 10/28/2017 10/20/2017 On Time
12 year report 10/28/2018 10/09/2018 On Time
13 year report 10/28/2019 10/23/2019 On Time
final report 12/28/2020 12/31/2020 Overdue/Received


Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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