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 study is a prospective non-randomized observational study,with a primary objective of comparing high molecular
weight von Willebrand factor multimer levels in nonpulsatile versus pulsatile left ventricular assist device recipients.
Study Population Description
Study Population: Patients who are identified pre-implant in the INTERMACS database as "Bridge to Transplant
(patient currently listed for transplant)" or "Possible Bridge to Transplant - Likely to be eligible" will be enrolled in the post market study. Patients implanted with the Heartmate II will comprise the study group and patients implanted with any other LVAD will comprise a concurrent comparator group.
Sample Size
10 nonpulsatile and 5 pulsatile (HeartMate XVE, Thoratec PVAD) for a total sample size of
15 patients
Data Collection
Primary endpoint is to examine the change high molecular weight mutlimer von Willebrand factor from
pre-operative levels in nonpulsatile and pulsatile device recipients to 7 days post procedure. Secondary endpoint examine HMW multimer vWF levels in patients who experience a bleeding event.
Followup Visits and Length of Followup
All subjects will be assessed pre-procedure and 7days, 30 days and 6 months after device
implantation (and/or preheart transplant and 7 days after heart transplant)
Final Study Results
Actual Number of Patients Enrolled
53 enrolled (36 included in analyses)
Actual Number of Sites Enrolled
2
Patient Followup Rate
18/52
Final Safety Findings
All non-pulsatile VAD patients demonstrated significant reductions in vWF HMW multimer levels following VAD placement.
By 30 days postimplantation 100% of non-pulsatile patients tested had reduction in their HMWM levels and AvWS. Therefore, there are additional factors related to AVWF beyond decreased HMVM.
1. Higher vWF Ag levels pre-implant were measured in the pulsatile recipients versus non-pulsatile and decreased slightly by 30 days post-implant in both.
2. VWF Ag levels were higher in the bleeders at all time points in non-pulsatile patients; and both bleeders and non-bleeders had lower 30 day and 6 month vWF Ag levels compared to pre-implant levels.
3. P-selectin levels did not change significantly from baseline following non-pulsatile pump implantation. P-selectin levels were significantly lower in non-bleeders prior to implant and at 30 days post-implantation.
4. D-dimer levels declined following surgery but remained elevated through the 12 months follow up measurements.
Study Strengths and Weaknesses
Weaknesses: First, there were too few patients in the pulsatile group to power the study.
Protocol deviations resulted in only 4 of the 10 pulsatile pumps being included. Of the 4 pulsatile pumps in the study, 3 patients recevied the HeartMate XVE and 1 received the Thoratec PVAD. Second, it was unclear if the loss of large mutlimers was inside or outside of the normal range of values for multimers seen in populations not included in the study.
Strengths: This study is hypothesis generating for future research to see if certain preoperative characteristics, such as high P-Selectin and high vWF levels, could help to identify patients who could be at an increased risk of bleeding postoperatively.
