A multicentre clinical trial to assess arteriovenous fistula (AVF)-first and arteriovenous graft (AVG)-first access strategies in older end-stage renal disease (ESRD) patients on haemodialysis has been deemed feasible following a two-year pilot study investigating the same topic.
The findings of the pilot study were presented at the 12th Congress of the Vascular Access Society (VAS; 6–9 April 2021, online), and demonstrated an average cannulation success rate of 55% following AVF-first or AVG-first access placement surgery—while primary access failures were observed in nine (31%) of the 29 participating patients.
“Our Kaplan-Meier event curves for AV access primary failures showed that most of the graft primary failures occurred in the early post-operative period, while most of the fistula primary failures became apparent in the later post-operative period,” said Mariana Murea, associate professor of nephrology at Wake Forest School of Medicine (Winston-Salem, USA), and the study’s presenting author.
“And, the time to successful access cannulation was also shorter in the graft group compared to the fistula group.”
The parallel-group, open-label pilot study was conducted between September 2018 and September 2020 at 16 outpatient dialysis units affiliated with the Wake Forest healthcare system, and was sponsored by the US National Institute on Aging (NIA).
Its main objective was to determine the feasibility of enrolling and randomising older adults with advanced kidney disease to a surgical intervention of either AVG—the intervention group—or AVF—the comparator group—as well as informing the future design and conduct of a multicentre clinical trial to compare the safety and effectiveness of both access placement strategies in older populations.
Patients considered eligible to be enrolled in the study were therefore aged 65 years or older, receiving haemodialysis for incident ESRD via a central venous catheter (CVC), and surgically-eligible to receive either an AVG or AVF access. Patients who had received a previous AV access creation were not considered eligible.
Over an 18-month recruitment period, 36 eligible patients consented and were enrolled in the pilot study, with 18 being allocated to an AVF-first access group and 18 being allocated to an AVG-first access group. A total of seven patients did not undergo their assigned surgical access placement in the trial for various reasons, meaning 16 participants ultimately underwent AVF placement surgery, and 13 underwent AVG placement surgery.
According to Murea, outcomes including gait speed, grip strength, pain at the AV access site, patient-reported satisfaction and kidney disease health-related quality of life were assessed multiple times throughout the 24 weeks after the initial access placement procedure. Cannulation of an AV access in the study was considered successful if it became the patient’s sole haemodialysis access, and their CVC was removed, while primary failure of the AV access was seen as either immediate, early, or late, depending on if access failure was observed at 48 hours, three months or six months respectively after the placement.
Under these considerations, successful cannulation was observed in eight (50%) of the 16 patients who underwent AVF placement surgery, with five (31%) demonstrating either early or late primary access failure. Successful cannulation was also observed in eight (62%) of the 13 patients who underwent AVG placement, while four (31%) demonstrated primary access failure.
This resulted in an overall successful cannulation rate of 55% across both types of placement surgery, with successful cannulation being observed in 16 of the 29 participants, and early or late primary access failure being observed in nine (31%). The median time taken to complete these successful cannulations was 113.5 days in the AVF group and 75 days in the AVG group, averaging out at 95 days across all 29 of the patients who underwent AV access placement surgery.
Regarding adverse events, Murea stated that three deaths occurred during the trial, accounting for more than 10% of the participants who underwent access placement surgery. Two of these were in the AVG-first group, while the other was in the AVF-first group. Murea also said the rates of catheter-related bloodstream infections (n=4; 31%) and AV access infections (n=3; 23%) observed were higher in the graft group when compared to the two occurrences (13%) of each of these infections types in the fistula group.
The study’s researchers concluded that there was a high prevalence of morbidity and mortality burden (27%) preventing AV access surgery in older patients with incident ESRD observed during the trial. Despite this, they deemed the enrolling and randomising of older adults with ESRD into a trial to assess surgical placement of AVF vs AVG to be feasible, but qualified this by adding that older patients with incident or prevalent ESRD, and patients who have previously received AV access surgeries in their life, should also be included in any future, larger-scale clinical trial. The need to reduce the frequency of questionnaire-based assessments in future trials was also listed by Murea as one of the key lessons learned during the pilot study.
With regard to its primary intention of assessing the feasibility of a larger study, Murea said the pilot study achieved its a priori feasibility criteria for patient enrolment rate (78%), intervention rate (81%) and retention rate (90%), and concluded that the study can now proceed—with design modifications—to a multicentre clinical trial.
Murea stated that a proposal for setting up a larger, multicentre randomised controlled trial (RCT) involving six different academic health systems had already been submitted to the NIA in June 2020, with a recruitment goal of 262 older dialysis patients over a period of three years having already been identified. Under the proposed trial, half of these patients will undergo AVG placement surgery, while the other half will undergo AVF placement.
The aims of the multicentre RCT, according to Murea, will include comparing the effectiveness and safety of both AVF and AVG access interventions—by looking at rates of catheter-free days and access-related infections—as well as assessing healthcare costs, patient-reported outcomes, and the relationship between pre-operative frailty and AV access failure, for each.