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.
Prospective, open-label, multi-center cohort study
Study Population Description
Newly Enrolled Post-approval Study Population
Consecutive patients who are eligible to receive a ION Stent as
indicated by the product labeling will be evaluated for enrollment into the study ION US Post Approval Study (PAS). Only those participants in the PAS cohort that are identified as PERSEUS-like will contribute towards the primary endpoint and the main secondary endpoint. Data from the entire PAS cohort will be used in the additional secondary endpoints.
PERSEUS-like has been defined as all patients without acute MI, graft stenting, chronic total occlusion, in-stent restenosis, failed brachytherapy, bifurcation, ostial lesion, severe tortuosity, moderate or severe calcification by visual estimate in target lesion or target vessel proximal to target lesion, multivessel stenting, Reference Vessel Diameter (RVD) < 2.25 mm, RVD >
4.00 mm, lesion length > 28 mm, cardiogenic shock, acute or chronic renal function (serum creatinine > 3.0mg/dl or patient on dialysis).
PERSEUS-like TAXUS Element Population
The new PERSEUS-like ION US PAS cohort participants will be combined with the following extant cohorts of the TAXUS Element (ION) patients from the TAXUS PERSEUS Workhorse (WH) and Small Vessel (SV) Clinical Trials and the TAXUS Element PERSEUS-like patients from the TAXUS Element EU COA
study (TE-Prove). This will constitute the PERSEUS-like TAXUS Element total study population evaluated under the Primary Endpoint, Main Secondary Endpoint, and Diabetic Subset analysis.
The ION US PAS uses data from their newly enrolled subjects and other ION
enrolled ION PAS US cohort will be 1,115 subjects enrolled at up to 65
The ION population is expected to be approximately 1,901 subjects with 12- month follow-up. This includes the 1,140 ION subjects from the TAXUS PERSEUS WH and SV Clinical Trials with 12-month follow-up, 360 ION PERSEUS-like subjects from the TAXUS Element EU COA study (TE-Prove) and approximately 401 ION PERSEUS-like subjects from the ION US Post-
To allow for approximately 3.5% attrition per year, 2,012 PERSEUS-like subjects will be required to provide at least 1,660 PERSEUS-like subjects through 3-year follow-up. This will include 1,166 subjects enrolled in the TAXUS PERSEUS WH and SV Clinical Trials, 400 ION PERSEUS-like subjects from the TAXUS Element EU COA study (TEProve) and approximately 446
ION PERSEUS-like subjects from the ION US Post Approval Study. Assuming that 40% of the total enrolled population is on-label subjects, a total enrollment of 1,115 subjects will be required in the ION US post-approval study.
The 12-month CD/MI rate for ION
Annual increase in Academic Research Consortium (ARC) (definite/probable)
ST rate in the PERSEUS-like ION population, starting at 24 months.
Additional secondary endpoints include:
1. Stent Thrombosis (ST) rate, using Academic Research Consortium (ARC) definition (definite/probable) in the following populations: overall subject population, ION on-label subject population and off- label subject population.
2. Rate of longitudinal stent deformation.
3. Overall and ION stent-related MACE rates (cardiac death, MI, TVR).
4. Overall and ION stent-related cardiac death or MI rates.
5. Overall and ION stent-related target vessel failure (TVF) rates.
6. Overall and ION stent-related TVR rates.
7. Overall and ION stent-related cardiac death rates.
A total of 1,111 subjects were enrolled in the ION post-approval study.
The ION PERSEUS-like population
for the primary and primary secondary endpoint analysis (n=1,789)
comprised of 1,166 subjects enrolled in the TAXUS PERSEUS Workhorse and Small Vessel Clinical Trials,
306 ION PERSEUS-like subjects from the TAXUS Element EU COA study and 317 ION PERSEUS-like subjects from the ION US Post Approval Study.
Actual Number of Sites Enrolled
Patient Followup Rate
At two years the follow-up rate was 92.26% (1025/1111).
This study was originally designed to follow-up
the subjects five years post-procedure. The study follow-
up was reduced to two years post-procedure because available long-term evidence showed that the rate of late stent thrombosis for this device was not expected to substantially increase after 2 years.
Final Safety Findings
The annual increase in Academic Research Consortium (ARC)-defined (definite/probable) stent thrombosis (ST) for the ION
stent from the pooled ION PERSEUS-like subjects is 0.23% (4/1720) with an upper 1-sided 95% confidence interval of 0.37% which is less than the pre-specified performance goal of 1% (p<0.0001).
Final Effectiveness Findings
The overall cardiac death or myocardial infarction rate for the ION PERSEUS-like subjects is 2.3%
(40/1729) with an upper one-sided 95% confidence interval of 2.9% which is less than the pre-specified performance goal (p < 0.0001).
Study Strengths and Weaknesses
This study met its performance goals and had a large sample size. This study demonstrated
that the ION Paclitaxel-Eluting Coronary Stent System had a rate of ARC-definite/probable ST to be significantly less than 1% year-to-year. The study also had a low rate of attrition, thus minimizing selection bias. Subject follow-up was only for two-years. However, this device has been assessed long-term in other studies.
Recommendations for Labeling Changes
A labeling change is not recommended because the results of this post-approval study are consistent
with those of the PERSEUS Clinical Trial Program. The current label of the ION Paclitaxel-Eluting Platinum Chromium Coronary Stent System includes longer-term (5 years) results on the PERSEUS Clinical Trial Program.