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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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Continued Follow-Up (HW-PAS-03)


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General
Study Status Progress Adequate
Application Number P100047 / PAS003
Date Current Protocol Accepted 02/14/2014
Study Name Continued Follow-Up (HW-PAS-03)
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source New Data Collection
Comparison Group No Control
Analysis Type Descriptive
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description Multicenter, prospective, a continued follow-up study consisting of patients from the HeartWare Trials under IDE G070199
Study Population Description patients at risk of death from refractory, advanced heart failure and implanted with a HVAS under IDE G070199
Sample Size at the time of PMA and Protocol approval a total of 152 patients (30 from the HW 003 BTT study and 122 from the CAP study) were potentially eligibile for participation
Data Collection Main: Transplant, explant, death

Observational: Overall survival on device, Final patient status, Re- hospitalizations, INTERMACS adverse events, Quality of Life (QOL) measures (KCCQ and EuroQol EQ-5D-5L), Functional Status (NYHA and 6- minute walk (6MW)).
Follow-up Visits and Length of Follow-up 5 years post implant of original device and every 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled This study included a. 22 Bridge to Transplant (BTT) subjects and b.

79 Continued Access Program (CAP) subjects

Actual Number of Sites Enrolled The HeartWare Continued Follow-Up Post Approval Study 3 (HWPAS-

03) enrolled 25 study sites

Patient Follow-up Rate The overall follow up rate for this study is 62.4% (n=63/101), with 3 patients voluntarily

withdrawing and 1 patient relocating to a non-PAS-enrolled site. 35 patients (34.65%) died during the

study. In the BTT cohort, 14 patients (63.6%) completed the study and 8 (36.4%) patients died during

the study. In the CAP cohort, 49 patients (62.0%)completed the study, 3 patients (3.8%) (n=) voluntarily

withdrew, 26 patients (32.9%) died during the study and 1 patient (1%) r
Final Safety Findings The safety endpoints of interest are overall survival on device, final patient status, re-hospitalization and

INTERMACs-defined adverse events.

Overall Survival on Device

The Kaplan-Meier survival rate is 50.3% for the 20 month follow-up period that the BTT patients were

followed in HW-PAS-03. For the CAP cohort, the Kaplan-Meier survival rate is 44.3% for the 54-month

follow-up period in HW-PAS-03.

Final Patient Status

For final patient status in HW-PAS-03, 67 patients were alive at study completion from both on-device

and off-device populations. 26 were still on the HeartWare ventricular assist device (HVAD) (21 on

original and 5 post-exchange) and 41 subjects alive after being explanted for transplant. 8/22 (36.4%)

and 26/79 (32.9%) died respectively for the BTT and CAP cohorts. Of the 34 who died, 64.7% died on the

original device, 17.6% died post-explant for transplant and 17.6% died post-exchange.

Rehospitalization

Seventy-eight patients out of 84 on original devices (92.9%) had at least one re-hospitalization while on device and 44 (52.4%) had 3 or more re-hospitalizations while on-device during the HW-PAS-03 study.

INTERMACS adverse events

There were 36/84 subjects (42.9%) who had 49 device malfunction/failure events on a HeartWare ventricular assist device (including post-exchange to another HeartWare VAS). Of those, 34 subjects (40.5%) had 44 serious device malfunction/failure events. The three most common adverse events were infection, device malfunction/failure and bleeding.

There were 16/84 HW-PAS-03 subjects (19.0%) who had 23 neurological dysfunction events on a HeartWare device (including post-exchange to another HeartWare VAS). Of those, 6 out of 84 subjects (7.1%) had seven CT confirmed ischemic cerebrovascular accidents (ICVAs), 9 out of 84 subjects (10.7%) who had 12 CT confirmed hemorrhagic cerebrovascular accidents (HCVAs), and 4 out of 84 subjects (4.8%) had four transient ischemic attacks (TIAs).

Final Effect Findings The effectiveness endpoints of interest are quality of life measures, functional testing scores (KCCQ, 6 Minute Walk Test and NYHA Class), NIH Stroke Scale, and the modified Rankin Score.

Quality of Life

The CAP cohort had a EQ-5D-DL score ranging from 70 at 18 months post-implant to 82 at 12 months post-implant. BTT cohort scores range from 58 at 60 months-post-implant to a high of 70 at 48 months post-implant.

Functional Testing

The average KCCQ score increased from 36.8 at baseline to 60.6 at 60-months post-implant. In the CAP cohort, the average KCCQ score increased from 36.9 at baseline to 57.6 at 60 months post-implant . The BTT cohort average KCCQ score increased from 36.6 at baseline to 66.4 at 60 months post-implant.

The overall average distance walked for the 6 Minute Walk Test increased from baseline at 55 meters to 200 meters at 60 months post-implant . In the CAP cohort, the average distance walked increased from 37 meters to 195 meters from baseline to 60 months post-implant. In the BTT cohort, it increased from 115 meters to 209 meters from baseline to 60 months post-implant.

Overall NYHA class changed from 95% NYHA Class IV at baseline to 5.6% NYHA Class IV at 60 months post-implant. In the BTT cohort, NYHA class change from 90.5% NYHA Class IV at baseline to 12.5% NYHA Class IV at 60 months post-implant. In the CAP cohort, NYHA Class changed from 96.8% NYHA Class IV at baseline to 0% NYHA Class IV at 60 months post-implant.

NIH Stroke Scale

Over 70% of the subjects completed the NIH Stroke Scale, with more than half of the visits having greater than 80% completion. The average NIH Stroke Scale score was between 0-0.5 at all timepoints where results were available, and no subjects reported a score greater than 6 at any timepoint.

Modified Rankin Score

Over 85% of subjects completed the mRS assessment at all timepoints, with most of the visits having over 95% completion. Over 75% of subjects who completed the mRS assessment had an mRS of 0 at all timepoints and over 90% of all subjects who completed the mRS assessment had an mRS less than or equal to 3 at follow-up timepoints. There were 14 incidences of an mRS score greater than 3 in 7 subjects total, including mRS assessments at the onset of a neurological dysfunction event or at enrollment into the PAS03 study.
Study Strengths & Weaknesses Strengths: The Heartware Continued Follow up Access HW-PAS-03 study patients is the first long-term follow-up study for adverse events past the standard premarket/IDE follow-up times. This study also uses INTERMACs adverse event definitions and captures the various adverse event proportions sufficiently and the high follow-up rate is reliable. There are few patients that are lost to follow-up or withdraw from the study.

Weaknesses:

Not all BTT and CAP subjects from the premarket/IDE cohort are followed in the PAS. Therefore, not all IDE patients that had adverse events were included in the PAS and are excluded from analysis. Only the healthy patients that survived and were enrolled in the PAS are included in the PAS, biasing the survival estimates if interpreted from implant to end of PAS study period.
Recommendations for Labeling Changes Yes


Continued Follow-Up (HW-PAS-03) Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
six month report 05/21/2013 05/20/2013 On Time
one year report 11/20/2013 11/13/2013 On Time
18 month report 05/21/2014 05/14/2014 On Time
two year report 12/19/2014 12/18/2014 On Time
three year report 12/20/2015 11/19/2015 On Time
four year report 11/19/2016 11/17/2016 On Time
five year report 11/19/2017 11/16/2017 On Time
final report 03/30/2018 03/29/2018 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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