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.
Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v
Silver Spring, MD
20993-0002
This was a prospective, randomized, controlled, multicenter, double-blind safety and efficacy study. Patients were randomized
in a 1:1 ratio to receive either the TAXUS Express Slow-Release paclitaxel-eluting stent system or an uncoated Express control stent. Randomization included stratification by clinical site, target lesion length (<18 mm versus >18 mm), and the presence or absence of medically treated diabetes mellitus. The primary objective of this study was to further evaluate the safety and effectiveness of the TAXUS Express Paclitaxel-Eluting Coronary Stent System in long lesion lengths, small and large vessel diameters and with multiple overlapping stents in the treatment of de novo coronary artery lesions.
Study Population Description
The device is indicated for improving luminal diameter for the treatment of de novo lesions
in native coronary arteries >2.25 to <4.0mm in diameter in lesions < 28mm in length.
Sample Size
1108 patients, 70 sites
Data Collection
Primary endpoint for this study is the rate of ischemia-driven target vessel revascularization at 9
months after the index procedure.
Followup Visits and Length of Followup
All patients were followed at 30 days, were to completed a 9-month follow-up evaluation, which
included angiographic assessmen and followed annually through 5 years post index procedure.
Final Study Results
Actual Number of Patients Enrolled
1172 patients, 586 Control and 586 Taxus
Actual Number of Sites Enrolled
70 sites
Patient Followup Rate
83%
Final Safety Findings
At the 5 year endpoint of the study, the TAXUS treatment group exhibited a statistically
significant excess of MI compared to the Control treatment group (5.6% in Control vs. 9.3% in TAXUS). In addition, the "Cardiac death and MI" rates across time though 5 years were statistically significantly different for the TAXUS group (13.5%) relative to the Control group (8.6%). The overall MACE rates (cardiac death, myocardial infarction [MI], and TVR rate) over time through 5 years were comparable between the TAXUS (30.6%) and Control groups (33.6%). The Cardiac death rates over time through 5 years were not statistically significantly different between the TAXUS (5.3%) and Control groups (3.6%). The per protocol stent thrombosis rates were similar between the two groups through 5 years (1.9% for TAXUS vs. 0.7% for Control). From 4 to 5 years, there were no ST events per protocol in either treatment group. The rates for all death through 5 years were comparable in the TAXUS (10.2%) and Control groups (8.5%). The serious adverse events rates through 5 years were comparable between the TAXUS and Control groups (71.1% in TAXUS vs. 73.4% in Control).
Study Strengths and Weaknesses
Strengths: Five year clinical follow-up was completed in 83.1% of all patients enrolled and eligible
for follow-up (871/1048). Weaknesses: The main area of concern is the higher MI rate in the TAXUS versus the control group
Recommendations for Labeling Changes
The high rates of MI and cardiac death or MI at five years in TAXUS
patients compared to BMS patients with a visually assessed RVD > 2.5 mm and lesion length >26 mm with > 2 planned stents are notable. The sponsor has been asked to include this data in the label.
