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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 f/u of the premarket cohorts

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Study Status Progress Adequate
Application Number P130021 S002/ PAS001
Date Current Protocol Accepted 05/09/2017
Study Name Continued f/u of the premarket cohorts
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source New Data Collection
Comparison Group Concurrent Control
Analysis Type Descriptive
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description Extended follow-up study of all available subjects that were enrolled in the Medtronic CoreValve® U.S. Pivotal Trial and Continued Access Study who received the Medtronic CoreValve® System (MCS) or underwent surgical aortic valve replacement (SAVR).
Study Population Description High risk and extreme risk subjects currently consented to and enrolled in the Medtronic U.S. Pivotal Trial and Continued Access Study who received the MCS or underwent SAVR.
Sample Size All available subjects enrolled in the US Pivotal Trial, 394 subjects randomized to transcatheter aortic valve replacement (TAVR) and 401 subjects randomized to surgical aortic valve replacement (SAVR), and 76 roll-in subjects in all sites (up to 45) and approximately 2800 CAP subjects.
Data Collection The primary endpoint of all-cause mortality at 12 months in High Risk subjects is non-inferior to surgical aortic valve replacement (SAVR), has been met. Clinical outcomes will be characterized annually through 5 years.

The secondary endpoints through 12 months have been evaluated. The following secondary endpoints will characterize clinical outcomes annually through 5 years:

A. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) event rates via Kaplan-Meier. MACCE is defined as a composite of:

¿ all-cause death

¿ myocardial infarction (MI)

¿ all stroke, and

¿ reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

2. The occurrence of individual MACCE components event rates via Kaplan-Meier

3. Major Adverse Events (MAE) event rates via Kaplan-Meier

4. Conduction disturbance requiring permanent pacemaker implantation event rates via Kaplan-Meier

5. Change in NYHA class

6. Quality of Life (QoL) change using the following measures:

¿ Kansas City Cardiomyopathy Questionnaire (KCCQ)

¿ SF 12, and

¿ EuroQoL

7. Echocardiographic assessment of valve performance using the following measures:

¿ transvalvular mean gradient

¿ effective orifice area

¿ degree of aortic valve regurgitation (transvalvular and paravalvular)

8. Aortic valve disease hospitalization event rates via Kaplan-Meier

9. Cardiovascular deaths and valve-related deaths event rates via Kaplan-Meier

10.Strokes (of any severity) and TIAs event rates via Kaplan-Meier

11.Evidence of prosthetic valve dysfunction
Follow-up Visits and Length of Follow-up Annually through 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled 656
Actual Number of Sites Enrolled 41 study sites
Patient Follow-up Rate 96.2% at 5 years (152/158)
Final Safety Findings The Kaplan Meier (K-M) rate of all-cause mortality or major stroke in the extreme risk (ER) Pivotal Cohort at 60 months was 71.7% in Iliofemoral subjects and 72.6% in combine group. The KM rate for all-cause mortality at 60 months was 70.9% in Iliofemoral subjects and 71.6% in combine group. The KM rate of cardiovascular mortality at 60 months was 55.0% in Iliofemoral group and 55.8% in combine group.
Final Effect Findings The mean change in NYHA class at 60 month compared to baseline remained statistically significant with a mean reduction of -1.5 + 0.8 in Iliofemoral subjects and -1.4+0.8 in combine group (p<0.0001). The change in KCCQ overall summary score at 60 months compared to baseline remained statistically significant with a mean change of 21.2 ± 27.9 in Iliofemoral subjects and 21.2+27.0 in combine group (p<0.0001). The EOAs values remained stable throughout the follow-up visits and the EOA mean for all sizes was reported 1.83+0.64 cm2 at 60 months.
Study Strengths & Weaknesses The ER Pivotal trial compliance rate was high (i.e., 96.7%) at 5 years. The ER Pivotal trial met the primary endpoints and provided long term data. However, the KM rate of all-cause mortality was high (i.e., 71.6%) in the combine group at 5 years. These patients tended to have a worse baseline health condition with high STS score of 10.4 ± 5.6% (combined group) and this could have contributed to the high all-cause mortality. Given that all-cause mortality is an evaluable endpoint for the study, this data was captured. Thus, patient exit through death is likely to have less impact on the validity of the study results.
Recommendations for Labeling Changes The CoreValve System used for this study is no longer marketed – replaced by the EvolutR and then the EvolutPro. No labeling changes are recommended.

Continued f/u of the premarket cohorts Schedule

Report Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
one year report 01/17/2015 11/28/2014 On Time
two year report 01/17/2016 11/27/2015 On Time
three year report 03/17/2017 03/17/2017 On Time
Final Report for Extreme Risk Cohort 10/13/2017 10/13/2017 On Time
four year report 03/17/2018 03/15/2018 On Time
five year report 03/17/2019 03/13/2019 On Time
High risk final report 09/26/2019 09/26/2019 On Time
final report 01/29/2020 01/29/2020 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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