Intermediate Versus Standard Dose Enoxaparin to Prevent Venous Thromboembolism in Severe Trauma Patients: a Multicenter Double Blind Randomised Controlled Trial

N/ANot Yet RecruitingNCT07506473

University Hospital, Grenoble540 enrolled

Overview

Venous thromboembolism is a frequent issue in severe trauma patients. Guidelines for venous thromboembolism prevention include the use of pharmacological thromboprophylaxis, mainly with low-molecular-weight heparin, and/or mechanical thromboprophylaxis. However, a high incidence of venous thromboembolism is observed despite standard dose thromboprophylaxis (such as enoxaparin 40 mg once daily). An increase of the dose of anticoagulants could improve thromboprophylaxis in trauma patients. To date, two randomised trials have assessed the effect of weight-based low-molecular-weight heparin dosing vs. fixed dose in trauma patients. These pilot studies did not demonstrate a statistical difference between groups although there was a trend in favour of a lower incidence of deep vein thromboses with the increased dose low-molecular-weight heparin prophylaxis. However, both studies included non-severe trauma patients and the second study focused only on deep vein thromboses. Other studies suggested that a superior-than-standard dose of low-molecular-weight heparin, sometimes guided by the anti-Xa activity, decreases the incidence of venous thromboembolism in severe trauma without increasing bleeding events, but they were observational in nature. The hypothesis of the HEPTRAUMA trial is that, in severe trauma patients, a thromboprophylaxis with intermediate dose low-molecular-weight heparin (twice the standard dose) decreases the incidence of major venous thromboembolism compared to standard dose.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

540

Conditions

Severe Trauma Patient

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * All adult patients (age ≥18 years) admitted to an intensive care unit following trauma with an expected stay \>48 hours and a planned administration of LMWH. * Affiliation to the French social security system or European (CEAM) Exclusion Criteria: * Prehospital cardiac arrest * Hospital admission \>72 hours * More than one dose of prophylactic anticoagulant already administered since trauma * Renal failure defined by creatinine clearance of 30 mL/min or less (Cockcroft-Gault formula) * Body weight \>100 kg or \<45 kg * Indication for therapeutic anticoagulation * Major known thrombophilia (e.g. antiphospholipid syndrome, antithrombin deficiency) * Constitutional bleeding disorder (haemophilia, von Willebrand disease, coagulation factor deficiency, platelet disorder). * Thrombocytopenia inferior to 50 G.L-1 * History of heparin-induced thrombocytopenia * Study drug hypersensitivity * Limitation of life support, life expectancy ≤7 days or palliative care * Contraindication to the administration of anticoagulant according to the SPC (Active clinically significant bleeding or a condition associated with a high risk of bleeding, such as a recent haemorrhagic stroke, gastrointestinal ulcer, the presence of a malignant tumour at high risk of bleeding, recent brain, spinal or ophthalmological surgery, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intrarachid or intracerebral vascular anomalies.) * pregnant or breastfeeding woman * Inclusion in another experimental trial * Protected person (art. L1121-5 to L1121-8 of the CSP or art. 31 to 35 of European regulation 536/2014)

Locations (17)

CHU Angers

Angers, France

CHU Clermont Ferrand

Clermont-Ferrand, France

Hôpital Beaujon AP-HP

Clichy, France

CHU Grenoble Alpes

Grenoble, France

AP-HP Bicêtre

Le Kremlin-Bicêtre, France

CHRU Lille

Lille, France

Hôpital Edouard Herriot HCL

Lyon, France

HCL Lyon Sud

Lyon, France

Assistance Publique - Hôpitaux de Marseille

Marseille, France

CHU Montpellier

Montpellier, France

...and 7 more locations

Outcomes

Primary Outcomes

Composite of symptomatic deep vein thrombosis (DVT), proximal DVT, pulmonary embolism (PE).

Effect of intermediate-dose versus standard-dose enoxaparin on the 14-day risk of major venous thromboembolism (symptomatic proximal DVT or PE) in adult patients with severe trauma eligible for pharmacologic thromboprophylaxis. Analyses will be conducted in the ITT population using a competing-risk approach (death before VTE considered as a competing event).

Time frame: Within 14 days following randomisation after severe trauma

Secondary Outcomes

To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on the net clinical benefit combining major venous thromboembolism and major bleeding events

Composite of major venous thromboembolism, as defined in the primary endpoint, and major bleedings, defined by (i) the need for a haemostatic invasive procedure because of bleeding, (ii) the need for interruption of prophylactic enoxaparin for ≥48 hours because of bleeding, or (iii) bleeding in a critical organ within 14 days following randomisation after a severe trauma

Time frame: Within 14 days following randomisation

To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on the individual components of the primary outcomethe incidence of major bleeding and clinically relevant non-major bleeding as per ISTH definition

* Symptomatic DVT of the lower limb within 14 days following randomisation * Proximal DVT within 14 days following randomisation * Pulmonary embolism within 14 days following randomisation

Time frame: Within 14 days following randomisation

To evaluate the effect of intermediate versus standard dose LMWH on the incidence of major bleeding and clinically relevant non-major bleeding as per ISTH definition

Major or clinically relevant non-major bleeding, as per ISTH definition, occurring during or within 48h of the last dose of study drug

Time frame: During or within 48h of the last dose of study drug

To evaluate the effect of intermediate versus standard dose LMWH on the incidence of red blood cell transfusions within 14 days following randomisation after severe trauma (or until hospital discharge)

Number of red blood cell transfusions within 14 days following randomisation after severe trauma (or until hospital discharge)

Time frame: Within 14 days following randomisation (or until hospital discharge)

To evaluate the effect of intermediate versus standard dose LMWH on the incidence of major VTE and major bleeding at day 30 following randomisation after a severe trauma

Incidence of major VTE (as defined in the primary endpoint) and major bleeding (as per ISTH definition) at day 30 following randomisation after a severe trauma

Time frame: At day 30 following randomisation

To evaluate the effect of intermediate versus standard dose LMWH on the incidence of deaths at day 30 following randomisation

Death at day 30 following randomisation after trauma