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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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INTERMACS Companion


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General
Study Status Completed
Application Number P030011 S011/ PAS002
Date Current Protocol Accepted 11/27/2015
Study Name INTERMACS Companion
General Study Protocol Parameters
Study Design Prospective & Retrospective Study
Data Source External Registry
Comparison Group Concurrent & Historical Control
Analysis Type Analytical
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description This is a two armed (partially retrospective and partially prospective), multi center, non randomized, cohort registry study that uses the INTERMACS Registry to compare performance of the TAHt when supported with the Companion 2 Driver System vs. performance of the TAH쳌t when supported with the CSS Console.

The primary endpoint will be the comparison of the positive outcome rate for TAHt patients initially supported with the Companion 2 Driver System compared to the positive outcome rate for patients initially supported with the CSS Console (concurrent cohort). Positive outcome will be assessed at both three and six months post-implant, and is defined as transplant, transfer to Freedom Driver, or continuing on implant driver support. The hypothesis is that the C2 Driver is non-inferior in positive outcome rate to the CSS Console by a margin of 10 percentage points.”

“Secondary Objectives will be to provide descriptive statistics on enrollment, adverse events, and outcomes for all TAHt patients enrolled in the INTERMACS registry. Additionally, the positive outcome rate for all patients initially supported with the Companion 2 Driver System will be compared to the positive outcome rate of all patients initially supported with the CSS Console (cumulative cohort).

Study Population Description Patients in the INTERMACS Registry who are implanted with the TAH쳌t and used the C2 Driver System as their initial driver.

There will be 2 control groups used for comparison. One consists of all Patients in the INTERMACS Registry who are implanted with the TAH쳌t who used the CSS Console (cumulative cohort). The other consists only patients in the INTERMACS Registry who were implanted with the TAH쳌t after The C2 Driver System began to be used June 2012 (concurrent cohort).





Sample Size The study will be composed of 200 patients supported by the Companion 2 Driver System and all INTERMACS Registry patients supported by the CSS Console at the time that the sample size for the C2 Driver System reaches 200.
Data Collection The data will be collected as defined in the INTERMACS Protocol.

The primary endpoint of survival rate at 3 and 6 months post implant will be evaluated according to the hypothesis mentioned above. Secondary objectives include the analysis of the same hypothesis except the comparing the C2 Driver System to the cumulative CSS console cohort.

Follow-up Visits and Length of Follow-up 4 years

Per INTERMACS Registry (1 week, 1 month, 3 month, 6 month and every 6 months thereafter).
Interim or Final Data Summary
Actual Number of Patients Enrolled A total of 200 Companion 2 (C2) Driver and 89 CSS Console users were enrolled in the concurrent cohort; a total of 225 C2 Driver and 268 CSS Console users were enrolled in the cumulative cohort.
Actual Number of Sites Enrolled A total of 57 INTERMACS clinical sites contributed data. (Database Closure Date for the Final Report: June 30, 2017)
Patient Follow-up Rate The follow up rate through six months is 99.5% for C2 Driver users and 100% for CSS Console users (*only one patient, who was initially supported by the C2 Driver, was lost to follow-up.)
Final Safety Findings Mortality Data:

The positive outcome (“survival”) rate in concurrent cohort:

At 3 months: 65.5% for C2 Driver users (lower bound of 95% confidence interval=58.5%) vs. 77.5% for CSS Console users. The non-inferiority was not met.

At 6 months: 60.0% for C2 Driver Users (lower bound of 95% confidence interval=52.9%) vs. 74.2% for CSS Console users. The non-inferiority was not met.

For patients who did not achieve positive outcome (“no survival”), all occurrences were due to death.

The survival rate in concurrent cohort, stratified by pre-implant circulatory rescue intervention:

Patients with rescue intervention:

1. At 3 months: 58.4% for C2 Driver users vs. 79.2% for CSS Console users

2. At 6 months: 55.8% for C2 Driver users vs. 72.9% for CSS Console users

Patients without rescue intervention:

1. At 3 months: 69.9% for C2 Driver users vs. 75.6% for CSS Console users

2. At 6 months: 62.6% for C2 Driver users vs. 75.6% for CSS Console users

The survival rate in cumulative cohort:

At 3-months: 66.2% for C2 Driver users vs. 82.5% for CSS Console users

At 6-months: 60.6% for C2 Driver users vs. 78.4% for CSS Console users

Neurological Adverse Events:

The proportion of patients with neurological adverse events in concurrent cohort:

Through 3 months: 31.0% for C2 Driver users vs. 13.5% for CSS Console users

Through 6 months: 31.5% for C2 Driver users vs. 14.6% for CSS Console users

The difference in neurological adverse events appeared to be driven mainly by the difference in cerebrovascular accident (CVA) for the two groups.

The proportion of patients with CVA events (concurrent cohort):

CVA through 3 months: 26.5% for C2 Driver users vs. 7.9% for CSS Console users (P<0.0001)

CVA through 6 months: 27.0% for C2 Driver users vs. 7.9% for CSS Console users (P<0.0001)

The proportion of patients with CVA events (concurrent cohort), stratified by pre-implant circulatory rescue intervention:

Patients with rescue intervention:

1. CVA through 3 months: 26.0% for C2 Driver users vs. 6.3% for CSS Console users

2. CVA through 6 months: 26.0% for C2 Driver users vs. 6.3% for CSS Console users

Patients without rescue intervention:

1. CVA through 3 months: 26.8% for C2 Driver users vs. 9.8% for CSS Console users

2. CVA through 6 months: 27.6% for C2 Driver users vs. 9.8% for CSS Console users

Other Adverse Events: The study also compared the occurrence of eleven other adverse events in patients initially supported with the C2 driver to those initially supported with the CSS Console. These adverse events were: arterial non-CNS thromboembolism, bleeding, device malfunction, hepatic dysfunction, infection, pericardial drainage, psychiatric episode, renal dysfunction, respiratory dysfunction, venous thromboembolism and wound dehiscence. There was no statistically significant difference in the occurrence of these eleven adverse events between C2 driver users and CSS Console users through 3 months and through 6 months.



Study Strengths & Weaknesses Strength: The follow-up rate was high in the study; the data source used in the study represented real-world data.

Weaknesses: The study reported higher mortality and CVA adverse events for patients initially supported by C2 Driver System than those initially supported by the CSS Console. However, we do not know the causes for these observed differences. The summary results did not adjust for potential confounding factors, such as patient characteristics or device characteristics. The existing data in INTERMACS Registry are limited in that detailed device characteristics (e.g. driver operating parameters, driver history, previously reported driver issues) and comprehensive patient pre-implant characteristics were not captured. Furthermore, the study was not powered to detect a significant difference between C2 driver group and CSS Console group for the secondary adverse event endpoints.

Recommendations for Labeling Changes Yes. It is recommended that the label be updated to reflect the higher rates of unsuccessful outcomes and neurological adverse events in the C2 driver group compared to CSS Console group.


INTERMACS Companion Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
six month report 06/24/2014 06/24/2014 On Time
one year report 02/11/2015 02/18/2015 Overdue/Received
18 month report 06/24/2015 06/24/2015 On Time
two year report 01/25/2016 01/27/2016 Overdue/Received
three year report 12/24/2016 12/23/2016 On Time
42 month report 07/10/2017 07/10/2017 On Time
48 month report/final report 12/24/2017 12/22/2017 On Time


Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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