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.
This is a prospective randomized study. One arm will receive balloon angioplasty of the target
lesion only, and the other arm will receive balloon angioplasty plus the FLAIR Endovascular Stent Graft (referred to as the FLAIR group).
Study Population Description
Patients with hemodynamically significant stenosis (>50%) with clinical evidence of graft dysfunction (without thrombotic occlusion)
at the synthetic arteriovenous access graft anastomosis, who have a life expectancy of at least 25 months at enrollment, who meet administrative requirements for participation in the study, are at least 18 years old, whose target lesion meets appropriate anatomic criteria, and who are not characterized by any of the study's exclusion criteria.
270 subjects, 30 sites
Primary endpoints includ: 1) access Circuit Primary Patency (ACPP - defined as the interval following
the index procedure until the next access thrombosis or reintervention; it ends with a reintervention anywhere within the access circuit.); 2) Patency Function (IPF - defined as the time from the index study procedure to complete graft abandonment divided by the number of visits for a reintervention performed on the AV access circuit in order to maintain vascular access for hemodialysis at 12 months follow-up); 3) number of device and/or procedure related adverse events; Secondary endpoints include:: 1) Number of reinterventions until graft abandonment or through 12 months post-index procedure, 2) Postintervention Assisted Primary Patency, 3) Postintervention Secondary Patency, 4) Procedure Success, and 5) Incidence of major device-related adverse events through 30 days post index procedure.
Followup Visits and Length of Followup
Subject follow-up will occur at 30 days and 6, 12 and 24 months. Follow-up will
occur by telephone at 30 days, 6 months and 24 months. It will occur by office visit/review of dialysis records at 12 months. The following will be assessed at follow-up: arteriovenous graft status, repeat interventions to the access circuit and treatment area, and device and/or procedure related adverse events.
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
Final Safety Findings
Subjects with device- or procedure-related AEs at 12 months: Control group ¡V 6%; FLAIR group
¡V 27% Subjects with device- or procedure-related AEs at 24 months: Control group ¡V 6%; FLAIR group ¡V 33%
Final Effectiveness Findings
Primary endpoint # 1: Access Circuit Primary Patency (ACPP) Time period ACPP for PTA ACPP for FLAIR 12
months 0.110 [95% CI = 0.05-0.17] 0.240 [95% CI = 0.17-0.32] 24 months 0.055 [95% CI = 0.01-0.10] 0.095 [95% CI =0.03-0.16] p value = .007 (comparison of PTA with FLAIR), showing superiority of FLAIR at 12 months
Primary endpoint # 2: Index of Patency Function (IPF) Time period IPF for PTA IPF for FLAIR (months per intervention) (months per intervention) 12 months 4.4 +/- 3.5 5.2 +/- 4.1 24 months 5.3 +/- 5.2 7.1 +/- 7.0 p value for comparison of PTA with FLAIR at 12 months is .009, showing non-inferiority (7 days) for FLAIR compared with PTA.
Study Strengths and Weaknesses
Strengths: -Þ Excellent follow-up (98%) -Þ Prospective cohort study -Þ Randomization to control vs. subject group Weakness: -Þ Some measures
of safety were found to be inferior in the subject compared with the control group. A post-hoc analysis was required in order to cast some doubt on the significance of those findings.
Recommendations for Labeling Changes
Yes: Update label with primary safety and effectiveness endpoints