Paclitaxel-assisted balloon angioplasty of venous stenosis in haemodialysis access: PAVE RCT
Authors: Karunanithy Narayan , Robinson Emily J , Calder Francis , Dorling Anthony , Peacock Janet L , Wang Yanzhong , Gardner Leanne M , Robson Michael G 
Published: September 2021

Background
Reliable vascular access is essential for patients receiving haemodialysis. An arteriovenous fistula is the preferred option; however, these are prone to developing stenotic segments. These lesions are treated with angioplasty, but there is a high rate of recurrence. When the PAVE (Paclitaxel-assisted balloon Angioplasty of Venous stenosis in haEmodialysis access) trial was conceived, a number of small studies suggested that restenosis may be reduced by paclitaxel-coated balloons.

Objective
To test the efficacy of paclitaxel-coated balloons in arteriovenous fistulas.

Design
A randomised controlled trial.

Setting
Twenty UK centres.

Participants
Patients (aged ≥ 18 years) referred with a clinical indication for angioplasty of an arteriovenous fistula (212 patients in total, 106 per group).

Interventions
High-pressure plain balloon fistuloplasty was performed in all patients. In the intervention arm, the second component was insertion of a paclitaxel-coated balloon. In the control arm, an identical procedure was followed, but using a standard balloon.

Main outcome measures
The primary end point was time (days) to loss of target lesion primary patency. Secondary patency end points were time to loss of access circuit primary patency and time to loss of access circuit cumulative patency. Other secondary end points included angiographically determined late lumen loss, rate of binary angiographic restenosis, procedural success, number of thrombosis events, fistula interventions, adverse events during follow-up and patient quality of life.

Results
Primary analysis showed no evidence for a difference in time to end of target lesion primary patency between groups (hazard ratio 1.18, 95% confidence interval 0.78 to 1.79; p = 0.440). An adjusted secondary analysis with prespecified clinical covariates gave similar results (hazard ratio 1.11, 95% confidence interval 0.69 to 1.78; p = 0.664). Prespecified secondary outcomes included the time to intervention anywhere in the access circuit or the time until the fistula was abandoned. There were no differences in these patency-related secondary outcomes or in any other secondary outcomes, such as adverse events.

Limitations
The PAVE trial was not a fully blinded trial. It was impossible to ensure that treating radiologists were blinded to treatment allocation because of the appearance of the paclitaxel-coated balloon. The extent to which our findings can be generalised to patients with multiple lesions could be questioned, given the proportion randomised. However, if paclitaxel-coated balloons had been effective at a single lesion segment, then there is no plausible reason why they could not be effective in patients with multiple lesions.

Conclusions
There were no differences in primary or secondary outcomes. Following a plain balloon angioplasty, additional treatment with a paclitaxel-coated balloon does not provide benefit.

Future work
The reasons for differences between the results of the PAVE trial and of other studies deserve further analysis and consideration. Other interventions to prevent restenosis following a fistuloplasty are needed.

Trial registration
Current Controlled Trials ISRCTN14284759.

Funding
This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 13. See the NIHR Journals Library website for further project information.