Results of the ACCESS 2 study, evaluating arteriovenous fistula (AVF) outcomes following use of the Sirogen (Vascular Therapies) sirolimus-eluting collagen implant, have shown that the device failed to meet non-inferiority for clinical fistula maturation compared to control at six months.
Nicholas Inston (Birmingham, United Kingdom) delivered the results in a podium-first presentation during yesterday morning’s vascular access masterclass—where he commented that the trial’s failure to meet its primary endpoint may be attributable to the overperformance of the standard of care arm against expectations.
Sirogen was developed as a means of intraoperative local, perivascular drug delivery at the time of index AVF surgery to improve outcomes in patients requiring an AVF. The device consists of a sirolimus and collagen matrix for targeted local drug delivery, which is bioabsorbable within 12 weeks.
Despite an earlier randomised prospective multicentre study—ACCESS—showing no statistical difference between Sirogen and controls in prespecified endpoints, post-hoc analysis from the trial showed improved fistula maturation and secondary patency in patients with end-stage renal disease aged ≥65 years.
Investigators went on to initiate the ACCESS 2 study to validate these findings and further evaluate the effectiveness of Sirogen to improve outcomes in patients requiring an AVF. The multicentre randomised study enrolled 136 patients across 17 centres in the United States and the United Kingdom, with a primary endpoint of fistula maturation at six months.
Inston reported that 66.8% of patients in ACCESS 2’s Sirogen arm achieved clinical fistula maturation compared to 63.2% in the control—representing a 3.6% point improvement—but falling short of the 18% point improvement goal set for the trial. Comparing against past studies, Inston said that Sirogen performed largely in line with previously observed results, but the performance of the control arm versus historical benchmarks ultimately tipped the dial towards primary endpoint failure.
“Unfortunately, we failed to meet the primary endpoint here and it is really due to this freaky outcome from the control group rather than anything else,” Inston said. “It is quite reassuring that the sirolimus group has performed as it has in all the other studies.”
Trial participants saw a 10-day mean time to functional maturation improvement; however, Inston said that a study involving thousands of patients would be required to study this outcome properly.
The trial remains blinded, with 12-month secondary endpoint data collection still in progress, and secondary endpoints, which include time to first dialysis, fistula suitability for dialysis and secondary patency, may provide additional important insights, according to Inston. “I think these might actually be more important than this simple primary endpoint. There will be number of interventions raised to get there, how will these be done, what type of interventions are required to keep this group going,” he explained.
