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
Workhorse (WH) Trial is a prospective, randomized, controlled, single blind, multicenter, non-inferiority trial
Small Vessel (SV)
is a prospective, single-arm, multi-center sub-study
Human Pharmacokinetics (PK) is a prospective, single-arm, multi-center, international, observational sub-study
Study Population Description
Continued follow-up of the premarket cohorts:
WH - Subjects with a maximum of 2 de novo
lesions ≤ 24 mm in length in native coronary arteries ≥2.50 mm to ≤4.25 mm. PROMUS Element (test) vs. PROMUS (control)
SV - Subjects with a single target lesion ≤28 mm in length in a native coronary artery ≥2.25 mm to <2.50 mm. PROMUS Element (test) vs. TAXUS Express (historical control)
PK - Subjects with a maximum of 2 de novo lesions ≤24 mm in length in native coronary arteries ≥2.50 mm to ≤4.25 mm
Approximately 85 sites in the US, 50 in Europe, 15 in the
IC region, and 10 in Japan
WH target lesion failure (TLF), MI, or death at 12 months
SV - TLF at
PK - whole blood everolimus levels as delivered by the PROMUS Element stent.
Followup Visits and Length of Followup
Through 5 years post-procedure
12 months, 18 months, 2 years, 3 years, 4 years, and 5
years after the index procedure
Final Study Results
Actual Number of Patients Enrolled
-WH Randomized Clinical Trial: 1530
-SV Subtrial: 94
-PK Subtrial: 22
Actual Number of Sites Enrolled
Actual number of study sites enrolled
-Workhorse (WH) Randomized Clinical Trial: 132
-Small Vessel (SV) Subtrial: 23
(PK) Subtrial: 5
Patient Followup Rate
-WH Randomized Clinical Trial: 94%
-SV Subtrial: 93.3%
-PK Subtrial: 100%
Final Safety Findings
-WH Randomized Clinical Trial: At the 5 year follow-up both the PROMUS Element and PROMUS/Xience
V stent had good safety rates with no significant difference between the groups in long term clinical outcomes. The PROMUS Element continued to trend toward numerically lower event rates for cardiac death (2.6% and 3.5% respectively). The cardiac death or myocardial infarction (MI) rate at five years for the PROMUS Element and the PROMUS Xience V were 6.2% and 5.7%, respectively. Academic Research Consortium (ARC)-defined (definite/probable) stent thrombosis (ST) at five years was similar among both groups (0.8% and 0.7% respectively).
-SV Subtrial: The cardiac death or MI rate at five years for the PROMUS Element small vessel was 7.0%. No ST events were observed in the study.
-PK Subtrial: There was no death, MI or ST observed during the length of the study.
Final Effectiveness Findings
-WH Randomized Clinical Trial: the 12-month target lesion failure (TLF) primary endpoint was met, indicating
non-inferiority of the PROMUS Element stent (3.4% [25/731]) versus the PROMUS/XIENCE V stent 2.9% [21/714], p=0.0013). At the 5 year follow-up, both the PROMUS Element and PROMUS/Xience V stent had low rates of revascularization with no significant difference between the groups in long term clinical outcomes.
-SV Subtrial: The 12-month TLF primary endpoint was met. The TLF rate at 12 months was 2.4% (2/84) with an upper 1-sided 95% confidence interval of 7.31% which is less than the pre-specified performance goal of 21.1% (p<0.0001).
-PK Subtrial: There were no target vessel revascularizations reported.
Study Strengths and Weaknesses
-WH Randomized Clinical Trial: This was a large (>1,500 subjects) randomized clinical trial with a
low rate of attrition; therefore, confounding and selection bias were minimized. This study met its primary endpoint and provides longer-term (5-year) performance data for the PROMUS Element Everolimus-Eluting Coronary Stent System.
-Both SV and PK subtrials provide longer-term (5-year) performance for the device although they have small sample sizes.
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-year) performance of the device.
OSB Lead-Continued F/u of Premarket Cohort