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.
Transit. Adolescent B (as adults) : 18-21 yrs,
Detailed Study Protocol Parameters
Study Design Description
This is a prospective, multi-center study designe to further understand Endeavor stent treatment patterns and
clinical outcomes in broad, unselected patient populations in North America, and to understand North American physician prescription patterns of dual antiplatelet therapy and implications of compliance with dual antiplatelet therapy.
Study Population Description
This device is indicated for improving coronary luminal diameter in patients with ischemic heart disease
due to de novo lesions of length < 27mm in native coronary arteries with reference vessel diameters of > 2.5mm to < 3.5 mm. Study subjects with ischemic heart disease due to stenotic lesions in either native coronary arteries or coronary artery bypass grafts undergoing percutaneous coronary intervention with stent placement are eligible to be enrolled in this study. Subjects may have multi-vessel treatment. Patients eligible for randomization into the CPI should not have contraindications to prolonged dual antiplatelet therapy noted at the time of randomization.
A minimum of 2,000 patients and a maximum of 4,000 patients, 100-150 sites
Endpoints that will be analyzed include: 1) definite and probable stent thrombosis at one year;
2) Combined rate of cardiac death and MI at one year; 3) Composite of death, target vessel MI, stroke, and major bleeding (severe or moderate per GUSTO classification) at one year; and 4) dual antiplatlet therapy compliance rates at each follow up interval to one year.
Followup Visits and Length of Followup
Patients will be followed at 3 , 6, 9, 12, 15, 18, 24, 30, and
33 months. The 12 month and 30 month follow-up include a clincal visit, 6, 9, 15, 18, 24, and 33 month follow-up involves telephone follow-up.
Final Study Results
Actual Number of Patients Enrolled
2262 patients were enrolled and followed from baseline. Of those enrolled, 1,440 patients were considered
12 months clear, (defined as thienopyridine compliant with no event prior to the 12 month time point) and from those, 811 provided consent to be randomized into the Critical Path Initiative (CPI) portion of the study and followed through 33 months.
Actual Number of Sites Enrolled
A total of 92 sites were included in this study.
Patient Followup Rate
At 12 months, the follow-up rate was 87.9%. For the non-randomized group at 24 months,
the follow- up rate was 99.6%. Finally, the CPI follow-up rate at 33 months was 99.7%.
Final Safety Findings
At one year, the Academic Research Consortium (ARC)-defined definite/probable stent thrombosis rate
was 1.3%. The combined
rate of cardiac death and myocardial infarction (MI) at one year was 3.8%. The rate of the composite endpoint, including death, target vessel MI, stroke, and major bleeding (severe or moderate per GUSTO classification) at one year was 7.4%.
The rates for all key endpoints including ARC definite/probable stent thrombosis, cardiac death/MI, and the composite endpoint (death, target vessel MI, stroke, and major bleeding) were consistently low (below 10%) across all groups except for the rate of the composite endpoint among the non- randomized subjects followed to 24 months. Results of this composite endpoint for all groups beyond
12 months are as follows: Non-Randomized at 24 months: 16.9%, CPI Intent-to-Treat (ITT) 12 months Dual Antiplatelet Therapy (DAPT): 5.9%, CPI ITT 30 months DAPT: 5.9%, CPI on-treatment (OT) 12 months DAPT: 1.7%, and CPI OT 30 months DAPT: 4.8%. The rates of cardiac death/MI and thrombosis were similar between the 12 month DAPT group and the 30 month DAPT group at 33 months.
Although not tested for significance, patients considered ¿complex¿ had higher rates of ARC definite/probable stent thrombosis, cardiac death/MI and the composite endpoint in comparison to non-complex patients.
Final Effectiveness Findings
Rates of DAPT usage and compliance were as expected and per protocol, indicating use of
placebo or thienopyridine in the randomized (CPI) portion of the study. DAPT compliance rates were 88.3% on the day of procedure, 98.1% at 30 days, 96.2% at 180 days, and 93.5% at one year.
The increased rate of DAPT use in the CPI ITT 12 month DAPT group (5.85%) and the decreased rate of DAPT use in the CPI ITT 30 month DAPT group (80.7%) may represent the management of events that occurred during this phase as well as subject medication use. On-treatment rates were as expected, however, with only 1.3% using DAPT among the 12 months DAPT group at 30 months, and 99.6% among the 30 month DAPT group at 30 months.
Study Strengths and Weaknesses
The study observed clinical outcomes in a broad unselected patient population during one year, and
up to 33 months in randomized subjects following PCI treatment to help define optimal duration of DAPT therapy. It also provides a background for future studies and analyses that will better and more definitively define optimal duration of DAPT therapy.
Limitations to this study may include the omission of subjects who had an event prior to one year, as
they are at most risk for subsequent complications from infarction or bleeding; as few, if any, studies are adequately powered to identify optimal DAPT duration, the omission is reasonable. This study was not powered to determine a treatment effect on clinical outcomes of different durations of DAPT treatment
Recommendations for Labeling Changes
A labeling update is not needed because Medtronic Vascular has ceased manufacturing and distribution of