ABSTRACT

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

The 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.

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

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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).

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Yes

Data Availability

Data will be made available on reasonable request.

AbbreviationsAEAdverse eventANOVAAnalysis of varianceCRFCase report formDHRADepartment of Health Risk AssessmentDOCADirect-acting oral anticoagulantDVTDeep vein thrombosisECTUEdinburgh Clinical Trials UnitEHITEndothermal heat-induced thrombosisGCPGood clinical practiceHATHospital-acquired thrombosisHEAPHealth economics analysis planHRAHealth Regulatory AuthorityHTAHealth Technology AssessmentICERIncremental cost-effectiveness ratioiDMCIndependent Data Monitoring CommitteeLMWHLow-molecular weight heparinMHRAMedicines and Healthcare Regulatory AgencyNHSNational Health ServiceNICENational Institute for Care and ExcellenceNIHRNational Institute for Health ResearchNNTNumber needed to treatPEPulmonary embolismPIPrincipal InvestigatorPPIPatient and public involvementPTSPost-thrombotic syndromeQALYQuality adjusted life yearsRATRisk assessment toolRCTRandomised controlled trialREDCapResearch Electronic Data CaptureRECResearch Ethics CommitteeSAESerious adverse eventSAPStatistical analysis planSMSShort message serviceTSCTrial Steering CommitteeUKUnited KingdomVTEVenous thromboembolism