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.
The HERCULES trial is a prospective, non-randomized, multi-center, single-arm clinical trial to demonstrate efficacy and
safety of the RX Herculink Elite Renal Stent System (Herculink Elite) in the treatment of suboptimal post-procedural percutaneous transluminal renal angioplasty (PTRA) of atherosclerotic de novo or restenotic renal artery stenoses in patients with uncontrolled hypertension.
Study Population Description
The population is entirely comprised of the existing 202-patient HERCULES study cohort.
The sample size and power calculation were based on the primary endpoint of binary restenosis
rate at 9 months. The OPC for the binary restenosis rate at 9 months was determined to be based on the ASPIRE-2 and SOAR clinical studies.
- Major Adverse Events: (death, nephrectomy, embolic events resulting in kidney damage) reported for all follow
up visits up to 36 months. - Target lesion revascularization (TLR) for all follow-up visits up to 36 months. - Primary patency rate at 24 and 36 months. - Secondary patency through 36 months for all visits. - Change in blood pressure, anti-hypertensive medication intake, and renal function for all follow up visits up to 36 months.
The binary restenosis rate at 9 months was 10.5% (22/209), with the upper one-sided 95%
CI of 14.7%, which was significantly below the pre-specified PG of 28.6% (p < 0.0001, exact binomial test).
Final Effectiveness Findings
3 year rates: -The freedom from TLR Kaplan-Meier Survival Analysis was 87.6%. -The study device, procedure, and
clinical success rates were high: 96.0% (237/247), 99.2% (238/240) and 98.0% (197/201), respectively. -Primary and secondary patency rates at 36 months were 82.9% and 95.8%, respectively. -There was a significant improvement in blood pressure from baseline. -There was no difference in the mean serum creatinine (sCr) and renal function from baseline.
Study Strengths and Weaknesses
Strengths - Outcome well below performance goal Weakness - High attrition rate (27%).