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
The PROTECT study is a prospective, multi-center, randomized, two-arm, open-label study.
The primary objective is to
compare the overall stent thrombosis rate of the Endeavor
Zotarolimus-Eluting Coronary Stent System versus the Cypher Sirolimus-Eluting Coronary Stent System in a patient population requiring stent implantation.
Study Population Description
This device is indicated for the improvement of the lumen diameter of carotid arteries in
patients considered at high risk for adverse events from carotid endarterectomy who require percutaneous carotid angioplasty and stenting for occlusive artery disease and meet the criteria outlined as follows:1. Patients with carotid artery stenosis (>50% for symptomatic patients by ultrasound or angiography or >80% for asymptomatic patients by ultrasound or angiography), located between the origin of the common carotid artery and the intra-cranial segment of the internal carotid artery; and 2. Patients must have a reference vessel diameter ranging between 4.8 mm and 9.1 mm at the target lesion. High-risk patients implanted with the Xact stent and Xact stent in the treatment of atherosclerotic carotid artery disease. The stent is used in conjunction with the Emboshield Pro Rapid Exchange Embolic Protection System and the Emboshield BareWire Rapid Exchange Embolic Protection System.
Sample Size
320 patients, 50 sites
Data Collection
The primary long-term endpoint is a composite of any death, stroke and myocardial infarction at
30 days plus fatal and non-fatal ipsilateral stroke from 31-365 days and annually thereafter for a total of 3 years. The secondary endpoints for this study include acute device success, procedural success at 30 days, composite of any transient ischemic attack and amaurosis fugax at 30 days, and annual rate of clinically driven target lesion revascularization through 3 years.
Followup Visits and Length of Followup
Annual follow-up through 3 years. No descriptions of enrollment and/or measures for handling follow-up are
included in protocol.
Final Study Results
Actual Number of Patients Enrolled
A total of 322 patients have been enrolled into the study.
Actual Number of Sites Enrolled
There are a total of 38 study sites that enrolled patients.
Patient Followup Rate
Follow-up rate is 75.2% (242/322).
Final Safety Findings
1) A total of six clinically driven target revascularization (TLR) events were reported in five patients.
The event free rate is 99.3% at one year, 98.2% at two years, and 98.2% at three years showing a higher (1.0~1.2%) event free percentage compared to the historical control group in the ARCHeR long term follow-up (LTFU) study.
2) Two point five percent (2.5%, 8/322) of patients experienced stoke and zero point nine percent (0.9%, 3/322) of patients experienced MI within 30 days post index procedure. Three point seven percent (3.7%, 12/322) of patients experienced stroke and four point seven percent of patients (4.7%, 15/322) experienced MI between 31 days and 3 years.
Final Effectiveness Findings
The primary endpoint was a composite of DSMI at 30 days, plus ipsilateral stroke between
days 31 and 365 and annually thereafter for 3 years. A total of 14 events were reported of which 11 events occurred within 30 days of procedure and 3 events occurred after 30 days during long-term follow-up. The overall composite event free rate is 96.6% at one year, 95.9% at two years, and 95.5% at three years showing a higher event free percentage at one-, two-, and three-year compared to the historical control group in the ARCHeR long term follow-up (LTFU) study.
Study Strengths and Weaknesses
Strength:
The study provides long term follow-up of patients at high risk for adverse events
from carotid endarterectomy implanted with the Xact stent in the treatment of atherosclerotic carotid artery disease.
Weakness:
1) Low percentage of minority group participants restricts the generalization of the results.
2) Only descriptive analysis is available for this study. No statistical tests are being made for the comparison of event free rate between the study cohort and the historical control group in the ARCHeR long term follow-up (LTFU) study.
Recommendations for Labeling Changes
Yes, labeling will be updated with the 3-year data.
