The Paclitaxel- or Sirolimus-Coated Balloons Used for Arteriovenous Fistulas-2 (PAVE-2) trial is underway to assess the efficacy of drug-coated balloons in maintaining the patency of arteriovenous fistulas (AVFs) in hemodialysis patients. This multicenter, randomized controlled trial compares paclitaxel-coated and sirolimus-coated balloons to uncoated control balloons following successful plain balloon fistuloplasty. The study aims to determine if drug-coated balloons can prolong AVF patency, reduce the need for repeat interventions, and improve patient quality of life.
Study Design and Objectives
The PAVE-2 trial is designed as a superiority trial, randomizing patients to one of three treatment arms: paclitaxel-coated balloon, sirolimus-coated balloon, or uncoated control balloon. The trial will recruit 642 patients with one or two treatment segments over a 3-year period, with a 1-year follow-up. The primary objective is to evaluate the time to loss of treatment segment primary patency (TSPP), defined as the patency of the vein segment treated during the initial plain balloon fistuloplasty without any re-intervention within 5mm proximal or distal to the treated area. Key secondary endpoints include time to loss of primary patency at any treatment segment, time to loss of access circuit primary patency, time to AVF abandonment, total number of interventions, adverse events, and patient-reported quality of life assessed using the EuroQol EQ-5D-5L and VASQoL surveys.
Patient Population and Inclusion Criteria
Patients undergoing hemodialysis with a surgically formed AVF in the arm, used for at least 8 dialysis sessions in the preceding 4 weeks, are eligible for the trial. Additional inclusion criteria include the need for fistuloplasty as determined by the local clinical team, absence of synthetic graft material or stents in the access circuit, and the ability to provide informed consent. Exclusion criteria include thrombosed access circuits, stenosis located centrally to the thoracic inlet, significant residual stenosis (more than 30%) after plain balloon fistuloplasty, and hypersensitivity to contrast medium, paclitaxel, or sirolimus.
Treatment Procedures
All patients undergo a plain balloon fistuloplasty using a high-pressure balloon sized to the nominal vein diameter to obliterate the lesion waist. Following successful plain balloon fistuloplasty, patients are randomized to receive either a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. Drug-coated balloons are inflated to nominal pressure for a minimum of 180 seconds. Image overlay/roadmap techniques are used to ensure precise treatment of the target segment. Completion fistulograms are performed to confirm the absence of angiographically visible effects after treatment.
Measures to Avoid Bias
Blinding is maintained where possible, with the treating radiologist and trial managers being aware of the treatment allocation. Patients, other radiologists, the direct care team, the site research team, and the trial statistician remain blinded. An independent radiologist reviews radiological interventions to adjudicate the primary endpoint. The Data Monitoring Committee (DMC) and Trial Steering Committee (TSC) may recommend unblinding based on interim analyses, while the statistician undertaking the primary efficacy analysis remains blinded.
Follow-Up and Data Collection
Study visits occur every 3 months for 1 year, involving assessments of access circuit interventions, changes to dialysis modality, adverse events, and quality of life. Ultrasound assessments are conducted at selected sites to measure intima-media thickness (IMT) and the degree of stenosis. Data collected include clinical notes, patient discussions, and medical history, with definitions provided for coronary artery disease, peripheral vascular disease, and stroke.
Safety and Ethics
Safety reporting adheres to requirements for research other than Clinical Trials of Investigational Medicinal Products. Serious Adverse Events (SAEs) related to the study treatment or access circuit are reported within 24 hours. The trial protocol has been reviewed and approved by the London-Hampstead Research Ethics Committee (REC), with HRA and Health and Care Research Wales (HCRW) approval.
