In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
Subject enrollment milestones not met,
Follow-up rate below 80%,
More than 10% of the primary endpoint data missing
General Study Protocol Parameters
Prospective Cohort Study
Study involve follow-up of premarket cohort (Y/N)
Objective Performance Criterion
Detailed Study Protocol Parameters
Study Design Description
Objectives: to characterize longer term (5 years) MitraClip device
performance by defining a) long term safety
and effectiveness, and b) patient and procedure characteristics that potentially lead to maximum benefit from the MitraClip device.
Design: a prospective, non-randomized, single-arm, multicenter, post-approval study using national TVT-Registry. This is a new enrollment study.
Study Population Description
The study will consist of a subset of at least 460 patients from the Prohibitive
Risk DMR Patient Registry (PAS 1). The PAS2 study Cohort will consist of 460 consecutively entered patients from these sites (up to 46 per site) who fulfill each of the following:
¿ significant symptomatic MR (≥ 3+) due to primary abnormality
of the mitral apparatus (DMR),
¿ Prohibitive risk for MV surgery as determined by a heart team, which includes a cardiologist experienced in MV disease and a cardiac surgeon experienced in MV surgery, and existing comorbidities that would not preclude the expected benefit from reduction of the MR.
¿ Ability to perform the 6MWT at baseline or be unable to perform the 6MWT due to cardiac reasons
Patients with unsuccessful implants or who fail to achieve MR reduction to ≤2+ but who otherwise meet the conditions above will not be excluded.
No comparator group.
Assuming 10% withdrawal at 12 months, a sample size of 460
patients from the Prohibitive Risk
DMR Patient Registry (PAS 1
Device Registry) is expected to provide 420 evaluable patients (not
lost-to-follow-up or discontinued) at 12 months post procedure.
Assumptions: The reported death rate at 30 days was 6.3% in the Prohibitive Risk DMR Cohort (Lim et al 2013); the all-cause mortality rate at 30 days was assumed to be 6.5%. The device- related complication rate was assumed to be ~6% at 12 months.
Because a majority of device-related complications are expected to occur within 30 days of the MitraClip procedure, the rate at 30
days was also assumed to be ~6%. Two thousand (2,000) simulations were performed to calculate sample size and power for the primary safety endpoint. A sample size of 420 evaluable patients provides >95% power to reject the null hypothesis at the
5% significance level.
Two thousand (2,000) simulations were performed to calculate sample size and power for the primary effectiveness endpoint. Assuming 37% attrition (25% death, 10% withdrawal, and 2% missing data) at 12 months, a sample size of 420 evaluable patients provides >95% power to reject the null hypothesis at the 5% significance level.
There will be a minimum of 15 sites and a maximum of 40 sites, with no more than 10% of patients (up to 46) from each site. Sites selected for participation in this study will be centers of excellence and experienced with performing and collecting 6MWT data and KCCQ data.
Main safety endpoints:
A composite of death and device-related complications at 30 days
post-procedure. The device-related complications
include single leaflet device attachment (SLDA), device embolization, device thrombosis, and other device-related events (e.g., endocarditis, MV stenosis), which result in MV re-intervention, unplanned other cardiac surgery, or unplanned vascular surgery or intervention through 30 days post-procedure.
Secondary safety endpoints:
All-cause mortality at 12 months, and device-related complications at 12 months.
Main effectiveness endpoints:
The change in 6MWT distance at 12 months over baseline.
Secondary effectiveness endpoints:
¿ MR severity at 12 months
¿ Change in LVEDV at 12 months over baseline
¿ Change in LVIDd at 12 months over baseline
¿ Change in KCCQ QoL at 12 months over baseline
NYHA Functional Class at 12 Months
Followup Visits and Length of Followup
Active follow-up of patients will be performed through 12 months