A Randomized Controlled Trial Comparing Crude Versus Heparin-Bonded PTFE Graft in Below the Knee Bypass Surgery for Critical Limb Ischemia (REPLACE Trial): Design and Protocol

Background: Although autogenous venous grafts are preferable for below-the-knee bypass surgery in patients with critical limb ischemia, some 20% of patients will have no suitable vein for grafting, compelling a resort to artificial graft materials. Retrospective subgroup analyses within published studies comparing heparin-bonded polytetrafluoroethylene (PTFE) with crude PFTE graft in below-the-knee bypass suggest that heparin-bonded graft offers superior long-term patency rates, but this has not been prospectively verified in patients with critical limb ischemia. Methods: A single-blind randomized controlled trial in 20 French centers has been designed. Patients assessed as having no suitable autologous vein for bypass grafting for critical lower limb ischemia will be randomized to receive either a heparin-bonded PTFE graft or a crude PTFE graft. A literature review suggested expected 1-year patency rates of 53% for the crude ePTFE arm and 74% for the heparin-bonded PTFEarm. Onanalyzing 1-year patency rate as a binary variable, for a significance level alpha = 0.05 and a randomization ratio of 1: 1, a total of 176 patients (88 in each arm) will be required to obtain approximately 80% power to reject the null hypothesis. Assuming 10% dropout at 1 year and 20% mortality, 228 patients will be randomized (114 patients in each arm). Results: The primary outcome variable will be patency at 1 year assessed by duplex ultrasound color-flow scan. Any intervention to open up or prevent a graft occlusion before 1 year will be classified as loss of patency. Technical success, deaths, complications, major adverse cardiovascular and limb events, length of hospitalization, and quality of life will also be recorded and analyzed as secondary outcome variables. Cost-utility and cost-effectiveness analyses based on standard tariffs in the French health insurance system will be performed. Conclusions: The REPLACE trial is the first randomized controlled trial designed to determine if heparin-bonded PTFE graft is superior to crude PTFE graft in below-the-knee bypass surgery for critical limb ischemia.