A multicentre, prospective, non-randomised, clinical trial was performed. Forty-six patients with clinically relevant access circuit stenosis were recruited from January 2019 through January 2020. The study was undertaken at three centres experienced with complex vascular access (Churchill Hospital, Oxford, UK; Queen Elizabeth University Hospital, Glasgow, Scotland; General Hospital of Athens “G. Gennimatas”, Athens, Greece). The trial is registered at clinicaltrials.gov (identifier: NCT03644017). The study followed good clinical practice guidelines and local regulatory requirements. An independent data monitoring/clinical event committee (DMC) was formed with three individuals with expertise in clinical trials and safety evaluations. The DMC reviewed and adjudicated reinterventions, access abandonments, as well as device and procedure-relatedness of adverse events.
The eligible population comprised patients undergoing HD through an AV circuit with clinical and radiological evidence of stenosis in the peripheral or central veins. Eligible patients required a mature AVF in the arm with ≥ 1 successful dialysis session or an AVG created ≥ 30 days prior. The target lesion was ≤ 9 cm in length with at least 50% stenosis. Patients with secondary lesions were excluded. Table 1 lists all eligibility criteria.
All patients provided written informed consent and were informed that they had the right to withdraw from the study at any time for any reason. Eighty-three patients were consented with 46 meeting the eligibility criteria and receiving treatment (consecutive enrolment). Enrolled patients included 16 patients with AVF and 10 with AVG and stenosis of the peripheral outflow veins (e.g. cephalic arch, basilic vein swing point); 9 with stenosis at the graft-vein anastomosis; and 11 with CVS. Figure 1 summarizes patient accountability. Tables 2 and 3 detail patient demographics and access circuit/target lesion characteristics. Tables S1 and S2 list patient’s concurrent medical conditions and anticoagulant/antiplatelet regimens.
WRAPSODY Endoprosthesis (Merit Medical Systems, Inc.; South Jordan, Utah, USA) is a self-expanding, cell-impermeable endoprosthesis. The endoprosthesis is composed of a helically wound nitinol wire stent fully encapsulated in a multilayer fluoropolymer covering (Fig. 2). The covering’s luminal layer is composed of a spun polytetrafluoroethylene (spun PTFE) designed to limit fibrin deposition and thrombus formation. The cell-impermeable middle layer is designed to prevent transmural cell growth. The outer layer is made of a traditional expanded polytetrafluoroethylene (ePTFE), permitting cell-ingrowth for device anchoring. The device is offered in various sizes, ranging in diameter from 6.0–16.0 mm (allowing treatment of vessels from 4.6–14.4 mm in diameter) and ranging in length from 30−125 mm.
Study Treatment and Follow-Up
Procedures were undertaken by four operators across the three sites, all with experience in interventional procedures. An uncoated standard angioplasty balloon (type and size left to site discretion) was used for pre-dilation. Full expansion of the pre-dilation balloon was required. Following pre-dilation, reassessment, and eligibility confirmation, patients were treated with the study device. To ensure adequate fixation and wall vessel apposition, devices were deployed in a 10–25% oversized configuration (vs. adjacent healthy vessel) with at least 1 cm overlap with healthy vessel or the synthetic graft. Devices were post-dilated with a balloon no greater than the endoprosthesis’ diameter. If multiple devices were deployed in an overlapped configuration, post-dilation of the first device occurred before deploying the second. If different sized devices were overlapped to accommodate vessel diameter changes, the smaller device was deployed first. Patients were treated and discharged according to each centre’s standard of care, including anticoagulant or antiplatelet administration. Table S4 summarizes device disposition.
An in-person physical examination was scheduled at 1, 3, 6, and 12 months post-procedure with additional visits as needed for assessment and treatment of access circuit dysfunction. Follow-up times were chosen to facilitate analysis over the critical period when current interventions fail. Physical examinations included at minimum an assessment of hand, arm, neck, and trunk oedema; pain related to dialysis circuit; respiratory and neurological symptoms; skin changes; and a review of AEs and interventions. The access circuit was also assessed for quality of flow.
The primary safety measure was the proportion of patients without any localised or systemic safety events affecting the access circuit during the first 30 days that resulted in surgery, hospitalization, or death. The primary effectiveness measure was the target lesion primary patency rate (TLPP) at 30 days. TLPP was defined as the interval of uninterrupted patency from initial study procedure to the next intervention performed on the target lesion or uncorrectable target lesion occlusion, whichever occurs first.
Secondary outcome measures included clinical (resumption of successful dialysis for at least one session), anatomical (less than 30% residual stenosis), and procedural success (achievement of both clinical and anatomical success). Device- or procedure-related adverse events and TLPP were further assessed at 3, 6, and 12 months. Assisted TLPP, access circuit primary patency (ACPP), and access circuit secondary patency were evaluated at 1, 3, 6, and 12 months. Table S4 contains a definition for each outcome measure.
Statistics and Data Corporation (SDC) and Clinlogix provided statistical analysis services for the study. Statistics were calculated using SAS (v9.4, SAS Institute Inc.). As this was a single-arm study, statistical analysis only included descriptive statistics (e.g. mean and standard deviation). Patency values were calculated using the Kaplan–Meier method. An interim analysis was preformed when all patients completed the 6-month visit.
Role of the Study Sponsor
Study devices were supplied by the sponsor. The sponsor was involved in establishing the study design; data collection, analysis, and interpretation; as well as the preparation of and decision to submit the manuscript. All authors confirm that they had full access to the study data and accept responsibility for publication submission.