|
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P190008 / PAS001 |
| Date Original Protocol Accepted |
11/14/2019
|
| Date Current Protocol Accepted |
03/04/2022
|
| Study Name |
IN.PACT AV Access IDE Cohort PAS
|
| Device Name |
IN.PACT AV Paclitaxel-coated Percutaneous Transluminal Angioplasty Balloon Catheter
|
| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
|
| Data Source |
Sponsor Registry
|
| Comparison Group |
Concurrent Control
|
| Analysis Type |
Analytical
|
| Study Population |
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The IN.PACT AV Access IDE Cohort Post Approval Study is a study that was initiated prior to device approval. It was designed as a prospective, global, randomized (1:1), multi-center clinical study that is ongoing at sites in the United States, New Zealand, and Japan.
|
| Study Population |
Subjects with a de novo or non-stented restenotic obstructive lesion up to 100 mm in length, located in the native arteriovenous dialysis fistulae.
|
| Sample Size |
330 subjects randomized in a ratio of 1:1 to either the IN.PACT AV Access DCB (study arm) or a standard PTA balloon (control arm).
|
| Key Study Endpoints |
The primary safety endpoint is defined as the serious adverse event (SAE) rate involving the AV access circuit through 30 days post-procedure. The primary effectiveness endpoint is defined as freedom from clinically-driven target lesion revascularization (CD-TLR) or access circuit thrombosis measured through 6 months post-index procedure.
|
| Follow-up Visits and Length of Follow-up |
Patients will be followed up to 60 months post-index procedure.
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
330
|
| Actual Number of Sites Enrolled |
16
|
| Patient Follow-up Rate |
As of the data cut-off on June 2, 2023: 96.6% (313/324) of eligible subjects completed the 30-day visit; 99.0% (309/312) of eligible subjects completed the 3 month visit; 96.7% (289/299) of eligible subjects completed the 6 month visit; 97.2% (276/284) of eligible subjects completed the 9 month visit; 94.4% (252/267) of eligible subjects completed the 12 month visit; 96.7% (236/244) of eligible subjects completed the 18 month visit; 95.5% (211/221) of eligible subjects completed the 24 month vi
|
| Final Safety Findings |
The primary safety endpoint was Serious Adverse Event (SAE) rate involving the AV access circuit through 30 days post-procedure. The 30-day SAE rate involving the AV access circuit was 4.2% in the IN.PACT AV DCB study group and 4.4% in the PTA control group. (unchanged from PMA).
New Data
Through 60 months, 35.9% (or 61 subjects) of subjects reported infections and infestations System Order Class (SOC) in the IN.PACT AV DCB study group and 27.5% (44 subjects) of subjects reported infections and infestations SOC in the standard PTA control group. In total, there were fifty-nine (59) deaths in the IN.PACT AV DCB study group and sixty (60) deaths in the Standard PTA control group.
|
| Final Effect Findings |
The primary effectiveness endpoint was target lesion primary patency through 6 months post-procedure. The 6-month target lesion primary patency rate was 82.2% in the IN.PACT AV DCB study group and 59.5% in the PTA control group (p<0.001). (data unchanged from PMA).
New Data
Abandonment of the Target AVF through 36 Months: There were a total of 14.5% (48/330) of AV Circuits abandoned through 36 months, 13.5% (23/170) in the IN.PACT AV DCB group, and 15.6% (25/160) in the Standard PTA group.
Number of Interventions required to maintain target lesion patency through 36 months: 254 for the IN.PACT AV DCB group and 289 in the Standard PTA group. Subjects with at least one intervention is 49.4% (84/170) for the IN.PACT AV DCB group and 66.3% (106/160) for the Standard PTA group (p=0.002).
Number of Interventions required to maintain access circuit patency through 36 months: 307 for the IN.PACT AV DCB group and 345 in the Standard PTA group. Subjects with at least one intervention is 57.1% (97/170) for the IN.PACT AV DCB group and 70.6% (113/160) for the Standard PTA group (p=0.010).
|
| Study Strengths & Weaknesses |
Strengths:
This study was a prospective, global, multicenter, single blinded, randomized clinical study. The sample size of 330 subjects provided adequate statistical power to achieve the primary objectives planned for the study. In order to provide a high-quality dataset that allows for a confident interpretation of the results, the overall data in this study was 90% monitored. Additional processes were employed to ensure the data quality and to minimize the reporting bias - the imaging data was adjudicated by independent imaging core laboratories. The study endpoint related major events including re-interventions, access circuit thrombosis, and all-cause deaths were adjudicated by an independent clinical event committee (CEC). Considering the additional efforts in collecting the subject’s vital status for those exited the study early, it provides an improved estimate in all-cause mortality through 60 months in this study cohort.
The study met the primary effectiveness endpoint for target lesion primary patency at 6-month, demonstrating superiority in the IN.PACT AV DCB study group compared to the PTA control group. The study also met the primary safety endpoint through 30-days with the pre-specified non-inferiority margin of 7.5%. No statistical difference in mortality was observed between the IN.PACT AV DCB and PTA control group through 60 months. The results continue to demonstrate the long-term safety and effectiveness of the IN.PACT AV DCB.
Weaknesses:
The study was originally designed for 24 months of follow-up. With the study extension to 60 months, a total of 16.4% (54/330) subjects declined consent beyond 24 months. In addition, due to the nature of the end stage renal disease (ESRD) condition in this study cohort, high proportions of the subjects exited the study before the 60-month study follow-up period mainly due to AV fistula abandonment, and withdrawal by subject. The other limitation was the sample size, that presented challenges in the subgroup analyses, such as the estimate of the safety and effectiveness outcomes by lesion type, AV type, lesion location, etc
|
| Recommendations for Labeling Changes |
Labeling changes will be recommended
|
