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.
OSB Lead-Cont Followup of Premarket and OUS Cohort
General Study Protocol Parameters
Prospective Cohort Study
Study involve follow-up of premarket cohort (Y/N)
Transit. Adolescent B (as adults) : 18-21 yrs,
Detailed Study Protocol Parameters
Study Design Description
These analyses will utilize the pooled data from the Global RESOLUTE Clinical Trial Program on-label
usage patients (RESOLUTE All Comers (R-AC) and RESOLUTE International (R-Int), RESOLUTE initial feasibility trial (R-FIM), the pre-approval trial for Japan, RESOLUTE Japan (R-J), and the RESOLUTE US (R-US)).
1) Demonstrate the safety in terms of stent thrombosis (ST) when the drug-eluting stent is used in accordance with the labeled indications from 12-24, 24-36, 36-48, and 48-60 months post implant. (36-60 months excludes R-Int)
2) Demonstrate the safety in terms of cardiac death (CD) and target vessel myocardial infarction (TVMI) when the drug-eluting stent is used in accordance with the labeled indications.
Study Population Description
The study population consists of four studies (R-FIM, R-AC, R-US, and R-J) with a five-year
follow-up and one study with a three year follow-up (R-Int).
The Global RESOLUTE Clinical Trial Program has currently amassed a dataset with a combined total of 5,130 subjects with follow-up at or greater than one year. This dataset consists of 2,349 Subjects considered to be ¿off-label¿ and 2,781 ¿on-label¿ subjects (Table 1).
Within the on-label subjects, a sample size of 1,312 will have 80% power to demonstrate
the rate of ARC definite probable ST to be significantly less than 1% year-to-year. The Resolute program will have 2,781 on-label subjects scheduled for three years of follow-up and 2,017 on-label subjects scheduled for four and five years of follow up. Therefore, the Pooled Resolute program will have a large enough sample size with or without the RESOLUTE International Registry subjects.
ARC definite or probable ST rates from 12-24, 24-36, 36-48 and 48-60 months.
rates up to 5 years post procedure.
Followup Visits and Length of Followup
Data collection will be annually up to 5 years of follow-up, except for R-Int (36 months)
The annual rate of Academic Research Consortium (ARC)-defined definite and probable stent thrombosis (ST)
at 5 years for on-label patients pooled from four studies (R-FIM, R-AC, R-US, and R-J) part of the Global RESOLUTE Clinical Trial Program was 0.02% (3/1937, upper 95% CI: 0.4%).
The 5-year cumulative rate of ARC- definite/probable ST through five years was 0.8% (15/1937) for on- label subjects and 2.5% (19/751) for complex subjects.
The 5-year cumulative rate of cardiac death or myocardial infarction for on-label and complex subjects pooled from four studies (R-FIM, R-AC, R-US, and R-J) part of the Global RESOLUTE Clinical Trial Program was 7.5% (145/1937) and 11.9% (89/751), respectively.
Final Effectiveness Findings
Procedural success: 97.9% (1961/2003)
Device success: 98.3% (2251/2289)
Lesion success: 99.9% (2283/2285)
Study Strengths and Weaknesses
This study provides longer term (5 years) safety and effectiveness results of the Resolute Zotarolimus-
Eluting Coronary Stent System. This study followed up the premarket cohorts through five years post- procedure. The study had a very low rate of attrition, thus minimizing selection bias. It demonstrated that the Resolute Zotarolimus-Eluting Coronary Stent System had a rate of ARC-definite/probable ST to be significantly less than 1% year-to-year. Although three of the four trials were conducted outside the US, 70% of the on-label subjects (1402/2017) were enrolled in the US. There were no complex subjects enrolled in US sites.
Recommendations for Labeling Changes
A labeling change is recommended to add a summary of the post-approval study results including
study strengths and limitations. The updated label will reflect the long-term (5-years) postmarket performance of the device.
OSB Lead-Cont Followup of Premarket and OUS Cohort