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 proposed study is a prospective non-randomized observational study, with subjects obtained from the INTERMACS
Registry, which included at least 84 sites with IRB approval as of December 31, 2007. The sponsor proposes to use the first 169 patients implanted with HeartMate II and the first 169 controls. If less than 169 control patients have entered the study by the time that 169 HeartMate patients have entered the study, consecutive controls will be chosen retrospectively.
Study Population Description
All 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. In addition, all other patients implanted with a HeartMate II during the post market study, who are not part of an IDE, and not "Bridge to Transplant (patient currently listed for transplant)" nor "Possible Bridge to Transplant - Likely to be eligible" will be analyzed as a separate group to help assess how the device is used in the community.
169 HeartMate patients and 169 controls from the INTERMACS Registry
Endpoints include: 1) procedural success, 2) incidence of adverse events. Bleeding adverse events will include
information on date and site of bleeding, anticoagulation use, and amount of blood transfusion, 3) Device malfunctions and failures, 4) Quality of Life as measured by EuroQOL (at 3 and 6 months), 4) Neurocognitive function (Trailmaking B), assessed in a subset of sites, detailed in a separate protocol, and 5) One year post explant survival.
Followup Visits and Length of Followup
All subjects and controls will be assessed at one week, one month, 3 months, 6
months, and one year post explant. Patients will be followed until one year post explant.
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
Final Safety Findings
The most common adverse events overall were bleeding, infection, cardiac arrhythmia, and respiratory failure. Compared
to the Comparison group, HMII patients had significantly lower risk for adverse events including device malfunctions. The most common type of device malfunction was ?external control system failure, 21 cases reported.
Final Effectiveness Findings
Success was defined as LVAS support for at least 180 days or to transplant, or
to explant due to myocardial recovery and survival for at least 60 days post explant. Ninety-percent (90%) of the HMII patients achieved success compared to 79% of the Comparison patients (Fishers exact P=0.0064).
Study Strengths and Weaknesses
Strengths: Follow-up rate was very high (99%); all subjects were prospectively followed; a concurrent control
group was available for comparison; all data was collected and evaluated through a registry that utilized standardized methods for data collection and evaluation.
Weakness: Potential confounding variables were not controlled for in comparing subjects with controls ? however, baseline data was similar in the two groups.
Recommendations for Labeling Changes
Labeling changes should be accomplished in accordance with the findings of the PAS.