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

Introduction Endovenous 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 analysis A 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 number ISRCTN18501431 ARTICLE SUMMARY Strengths and limitations of this study ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05735639 ### Funding Statement This work is supported by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR152877). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data will be made available on reasonable request. * AE : Adverse event ANOVA : Analysis of variance CRF : Case report form DHRA : Department of Health Risk Assessment DOCA : Direct-acting oral anticoagulant DVT : Deep vein thrombosis ECTU : Edinburgh Clinical Trials Unit EHIT : Endothermal heat-induced thrombosis GCP : Good clinical practice HAT : Hospital-acquired thrombosis HEAP : Health economics analysis plan HRA : Health Regulatory Authority HTA : Health Technology Assessment ICER : Incremental cost-effectiveness ratio iDMC : Independent Data Monitoring Committee LMWH : Low-molecular weight heparin MHRA : Medicines and Healthcare Regulatory Agency NHS : National Health Service NICE : National Institute for Care and Excellence NIHR : National Institute for Health Research NNT : Number needed to treat PE : Pulmonary embolism PI : Principal Investigator PPI : Patient and public involvement PTS : Post-thrombotic syndrome QALY : Quality adjusted life years RAT : Risk assessment tool RCT : Randomised controlled trial REDCap : Research Electronic Data Capture REC : Research Ethics Committee SAE : Serious adverse event SAP : Statistical analysis plan SMS : Short message service TSC : Trial Steering Committee UK : United Kingdom VTE : Venous thromboembolism