THRomboprophylaxis in Individuals undergoing superficial endoVEnous treatment: a multi-centre, assessor blind, randomised controlled trial – THRIVE trial

Abstract

ABSTRACTIntroductionEndovenous therapy is the first-choice management for symptomatic varicose veins in NICE guidelines, with 56-70,000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and endothermal heat-induced thrombosis (EHIT), are known complications of endovenous therapy, occurring at a rate of up to 3.4%. In an attempt to reduce VTE, 73% of UK practitioners administer pharmacological thromboprophylaxis. However, no high-quality evidence to support this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE, however, further evidence is needed. The aims of this study are to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective.Methods and analysisA multi-centre, assessor-blind, randomised controlled trial (RCT). We aim to recruit 6660 participants undergoing superficial endovenous interventions under local anaesthesia. Forty sites across the UK, both NHS and private, will be included. Participants will be randomised to either intervention (a single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21-28 days post-procedure to identify asymptomatic DVT. The ultrasound duplex scan will be conducted locally by blinded assessors. Participants will also be contacted remotely for follow-up at 7-days and 90-days post-procedure. The primary outcome is imaging confirmed lower limb DVT with or without symptoms, or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance (ANOVA), adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression.Trial registration numberISRCTN18501431ARTICLE SUMMARYStrengths and limitations of this studyThe study will serve as a large, randomised controlled trial providing grade A evidence on the most clinically- and cost-effective thromboprophylaxis regimen following superficial endovenous treatment.The primary outcome holds clinical significance.Using VTE prophylaxis may be associated with adverse clinical outcomes, increased risks and may not be cost-effective.Should pharmacological thromboprophylaxis be shown to offer no additional benefit to patients undergoing superficial endovenous intervention, stopping this practice has the potential to generate significant cost savings for healthcare providers.