Abstract: PO2532
ACCESS (NCT02513303): A Phase 3 US Multicenter Randomized Controlled Trial Evaluating Efficacy of a Perivascularly Delivered Sirolimus Formulation (Sirogen™) for Improving Hemodialysis AVF Outcomes
Session Information
- Late-Breaking Clinical Trials Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Vascular Access
Authors
- DeVita, Maria V., Lenox Hill Hospital, New York, New York, United States
- Kopyt, Nelson P., Lehigh Valley Health Network, Allentown, Pennsylvania, United States
- Khawar, Osman, Balboa Nephrology Medical Group, San Diego, California, United States
- Atray, Naveen K., Capital Nephrology Medical Group, Sacramento, California, United States
- Gandhi, Nirav, West Anaheim Medical Center, Anaheim, California, United States
- Hendon, Kendra S., Parkwest Medical Center, Knoxville, Tennessee, United States
- Lynn, Robert I., Albert Einstein College of Medicine, Bronx, New York, United States
- Iyer, Sriram, Lenox Hill Hospital, New York, New York, United States
Group or Team Name
- On behalf of the ACCESS Trial Investigators
Background
Lack of a prophylactic therapeutic for improving AV Fistula Suitability for Dialysis (FSD) is an unmet need. Sirolimus delivered locally to the vessel wall is a clinically proven anti-proliferative. Advancing age, female gender & comorbidities like coronary artery disease (CAD) are known risks for AVF maturation.
Methods
The Full Analysis Set (FAS) included 243 pts randomized 1:1; 125 Sirogen 118 Controls; 174 ESRD 69 CKD; 205 RCF 38 BCF. End points: Clinical FSD: AVF use with 2 needles with mean Qb ≥300 ml/min (2N/300) for at least 2/3rd of the HD sessions during a 30-day period starting day 150 (FSD6; Primary Endpoint) or day 330 (FSD12). Ultrasound FSD: outflow vein diameter ≥6mm, Qa ≥500ml/min; criteria used if CKD pt. was not on HD by day 150 or 330. Secondary Patency (SP): Fistula survival without abandonment; Fistula Maturation (FM): AVF use for 3 consecutive 2N/300 HD sessions.
Results
Age subgroup analysis provides explanation supported by data for endpoint results shown in Table. 2/3rd of randomized pts were <65y (lower risk). In ESRD pts ≥65y clear evidence of Rx effect (Figs 1,2); RCF outcomes were even more compelling. Exceptional control performance in <65y group masked treatment effect. No evidence of Rx failure. No safety concerns.
Conclusion
1. No differences in prespecified endpoints
2. Demographic differences & risk imbalance (bias favored controls) motivated a post hoc age subgroup analysis
a. <65y: Control overperformance (not Rx failure) negated endpoint differences & influenced overall outcomes
b. ≥65y: Maturation Benefit (FM) is significant & durable (FSD12, SP)
3. Confirmatory Trial is planned
FAS: Outcomes
| Characteristics | Sirogen | Controls |
| Age Mean (SD) y | 59.7 (14.9) | 57.7 (13.9) |
| Age ≥65y | 51 (40.8%) | 36 (30.5%) |
| Females No (%) | 28 (22.4%) | 23 (19.5%) |
| CAD No (%) | 50 (40%) | 30(25.4%) |
| FSD6* | 63.2% | 68.5% |
| FSD12* | 73.4% | 71.8% |
| SP* | 81% | 81.8% |
*p=ns
Funding
- Commercial Support – Vascular Therapies, Inc