THRomboprophylaxis in Individuals Undergoing Superficial endoVEnous Treatment (THRIVE)

Study Overview
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Brief Summary
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Endovenous interventions are keyhole operations for varicose veins that are carried out from within the vein itself. Varicose veins are enlarged veins close to the surface of the skin. They are connected to the bigger deeper veins in the leg (known as deep veins). Because of this, operations to close the varicose veins can increase the chance of a blood clot forming in the deep veins. Blood clots in the deep veins happen in around 1 in 50 people after endovenous operations. A clot in the leg can cause swelling, pain, and other long-term problems. If a clot in the leg breaks off and travels to the lungs, it can cause problems with the lung' ability to move oxygen from the air into the blood and may, in rare cases, be life threatening. Varicose vein procedures may carry a slightly higher risk of blood clot formation, and we are currently unsure if current clot reducing medicines are beneficial in preventing blood clots in people having varicose vein procedures. This study will investigate if it is worthwhile prescribing medicines to reduce blood clots after varicose vein procedures.

Official Title
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THRomboprophylaxis in Individuals Undergoing Superficial endoVEnous Treatment (THRIVE) - a Multi-centre Assessor-blind Randomised-controlled Trial

Conditions
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Venous Thromboembolism, Varicose Veins

Intervention / Treatment
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* Drug: Dalteparin Sodium
* Drug: Tinzaparin Sodium
* Drug: Enoxaparin Sodium
* Drug: Rivaroxaban
* Drug: Apixaban
* Drug: Dabigatran Etexilate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (>18 years) Scheduled to undergo endovenous intervention of truncal varicose veins under local anaesthesia Treatment technologies including radiofrequency, laser, mechanochemical, foam sclerotherapy and cyanoacrylate glue Exclusion Criteria: Clinical indication for therapeutic anticoagulation e.g., atrial fibrillation Previous personal or first-degree relative history of VTE Thrombophilia Female patients of childbearing potential who have a positive pregnancy test A history of allergy to heparins or direct oral anticoagulants A history of heparin-induced thrombocytopenia Inherited and acquired bleeding disorders Evidence of active bleeding Concomitant major health problems such as active cancer and chronic renal and/or liver impairment Known thrombocytopenia (platelets known to be less than 50 x 109 /l) Surgery or major trauma in the previous 90 days Recent ischemic stroke in the previous 90 days Inability to provide consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Compression therapy alone<br> | |
| Experimental: Compression therapy + single dose of low-molecular weight heparin at time of procedure<br>A single prophylactic dose of low molecular weight heparin (LMWH) (e.g., dalteparin sodium, tinzaparin sodium, enoxaparin sodium) will be prescribed as per standard practice and administered in accordance with the relevant Summary of Product Characteristics (SmPC), manufacturer's recommendations and instructions for use. | Drug: Dalteparin Sodium<br>* Low molecular weight heparin<br>Drug: Tinzaparin Sodium<br>* Low molecular weight heparin<br>Drug: Enoxaparin Sodium<br>* Low molecular weight heparin<br>|
| Experimental: Compression therapy + single dose of LMWH at time of procedure + extended course of LMWH or DOAC<br>An extended duration of LMWH (e.g., dalteparin sodium, tinzaparin sodium, enoxaparin sodium) or an extended duration of a direct oral anticoagulant (DOAC) (e.g., rivaroxaban, apixaban, dabigatran etexilate) will be prescribed as per current local practice and administered in accordance with the relevant SmPC, manufacturer's recommendations and instructions for use. The duration of this must be at least 7 days, but can be in line with local practice i.e., 7, 10 or 14 days. | Drug: Dalteparin Sodium<br>* Low molecular weight heparin<br>Drug: Tinzaparin Sodium<br>* Low molecular weight heparin<br>Drug: Enoxaparin Sodium<br>* Low molecular weight heparin<br>Drug: Rivaroxaban<br>* Direct oral anticoagulant<br>Drug: Apixaban<br>* Direct oral anticoagulant<br>Drug: Dabigatran Etexilate<br>* Direct oral anticoagulant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Imaging confirmed lower limb deep vein thrombosis (DVT) with or without symptoms, or pulmonary embolism (PE) with symptoms within 90 days of varicose vein treatment. | The rate of lower limb DVT with or without symptoms, or PE with symptoms within 90 days of varicose vein treatment. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower limb DVT without symptoms | Duplex ultrasound scan | 21 - 28 days | 
| Lower limb DVT with symptoms | Self-reported VTE outcome questionnaire | 90 days | 
| PE with symptoms | VTE outcome questionnaire (self-reported) to determine the rate of PE | 90 days | 
| Comparisons of quality of life at 7- and 90-days post-procedure | Using EQ-5D | 90-days | 
| Cost-effectiveness of providing pharmacological thromboprophylaxis | Incremental Cost-Effectiveness Ratio (ICER) | 90 days | 
| Exploratory analyses to assess how well a VTE risk assessment tool predicts VTE outcome | Venous thromboembolism risk as determined by the Department of Health Risk Assessment tool | 90 days | 
| Exploratory analyses to assess how well a VTE risk assessment tool predicts VTE outcome | Venous thromboembolism risk as determined by the Caprini risk assessment model | 90 days | 
| Mortality rates in each group | Rate of mortality | 90 days |