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 is a prospective, multi-site post-approval study involving previously implanted Tupos LV/ATx patients who participated
in the OPTION CRT/ATx Clinical Investigation. The purpose of this post-approval study is to collect long term survival and long term left ventricular (LV) lead data on patients previously implanted with the Tupos LV/ATx ICD and enrolled into the OPTION CRT/ATx (Cardiac Resynchronization Therapy and Atrial Therapy) clinical investigation.
Study Population Description
The study population consists of previously implanted Tupos LV/ATx patients who participated in the OPTION
CRT/ATx Clinical Investigation. These are patients receiving optimized and stable congestive heart failure (CHF) drug therapy, symptomatic CHF (NYHA class III/IV and LVEF <= 35%), intraventricular conduction delay (QRS 130 ms).
Sample Size
The post-approval study required following the existing OPTION Tupos LV/ATx patient cohort and did not
require enrollment of any new patients with Tupos LV/ATx CRT-D devices. Of the original 129 OPTION CRT/ATx patients successfully implanted with a Tupos LV/ATx, 49 patients still remained actively followed in the OPTION CRT/ATx study when FDA granted approval of the Tupos LV/ATx CRT-D device (P050023) on August 10, 2006. Therefore, since no new enrollment was planned, time to close enrollment is not applicable for this study as enrollment was closed as soon as all 49 active patients were approached and provided consent.
Data Collection
The post-approval study will report patient mortality, left ventricular (LV) lead capture thresholds and specific
left ventricular lead related complications, such as diaphragmatic stimulation and loss of left ventricular capture. In addition, data regarding the Tupos LV/ATx system status, the percentage of patients receiving CRT, and left ventricular lead adverse events will be collected.
Followup Visits and Length of Followup
The patients are followed every 3-months for a period of three years. The patient's follow-up
schedule is a continuation of the OPTION CRT/ATx follow-up schedule. The follow-up visits coincide with their routine ICD care.
Final Study Results
Actual Number of Patients Enrolled
Of the original 129 OPTION CRT/ATx patients successfully implanted with a Tupos LV/ATx, 49 patients
remained active for follow-up in the OPTION CRT/ATx study.
Actual Number of Sites Enrolled
19 sites
Patient Followup Rate
Of the original 129 OPTION CRT/ATx patients successfully implanted with a Tupos LV/ATx, 49 patients
remained active for follow-up (every 3-months for a period of three years) in the OPTION CRT/ATx study. Of the 49 patients enrolled in the post appr
Final Safety Findings
A total of 119 measurements in 47 patients were performed at routine and interim follow-ups.
The average left ventricular lead threshold at 0.5 ms pulse width was 1.7 V with a standard deviation of 1.1 V and a range of 0.5 to 6.0 V. Thirty-three percent of the patients had average thresholds 2.0V or more and 20% of the patients averaged 3.0 V or more. There were many explants due to the end of service life, accounting for 32 of the 34 reported complications. There is quite a bit of variability in the left ventricular lead threshold regardless of the variability associated with the small sample size. However, 80% of the final thresholds were < 3V, and 96% were < 4V.
Study Strengths and Weaknesses
Weakness: Of the 49 patients enrolled in the post-approval study, 10 withdrew consent, 4 died,
