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

April 23, 2026 updated by: University Hospital, Grenoble

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
540

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Angers, France, 49100
        • CHU Angers
        • Contact:
        • Principal Investigator:
          • Sigismond Lasocki
      • Clermont-Ferrand, France, 63000
        • CHU Clermont Ferrand
        • Contact:
        • Principal Investigator:
          • Benjamin RIEU
      • Clichy, France, 92110
        • Hôpital Beaujon AP-HP
        • Contact:
        • Principal Investigator:
          • Charles BERNARD
      • Grenoble, France, 38000
        • Chu Grenoble Alpes
        • Contact:
        • Contact:
        • Principal Investigator:
          • Alexandre GODON
      • Le Kremlin-Bicêtre, France, 94270
        • AP-HP Bicêtre
        • Contact:
        • Principal Investigator:
          • Inaame ETTOUMI
      • Lille, France, 59000
      • Lyon, France, 69003
        • Hôpital Edouard Herriot HCL
        • Principal Investigator:
          • Anne-Claire LUKASZEWICZ
        • Contact:
      • Lyon, France, 69310
        • HCL Lyon Sud
        • Principal Investigator:
          • Jean Stéphane DAVID
        • Contact:
      • Marseille, France, 13005
        • Assistance Publique - Hopitaux de Marseille
        • Contact:
        • Principal Investigator:
          • Gary DUCLOS
      • Montpellier, France, 34080
        • CHU Montpellier
        • Contact:
        • Principal Investigator:
          • Pauline DERAS
      • Nantes, France, 44000
      • Paris, France, 75013
        • Hôpital Pitié-Salpêtrière APHP
        • Contact:
        • Principal Investigator:
          • Pauline GLASMAN
      • Paris, France, 75015
        • Hôpital Européen Georges Pompidou AP-HP
        • Contact:
        • Principal Investigator:
          • Anne GODIER
      • Rennes, France, 35000
        • Chu Rennes
        • Principal Investigator:
          • Yoann LAUNEY
        • Contact:
      • Strasbourg, France, 67200
      • Toulouse, France, 31300
        • CHU de Toulouse
        • Contact:
        • Principal Investigator:
          • Véronique ROMANDA
      • Tours, France, 37000
        • CHU Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard Dose LMWH
Patients in the control group receive a standard dose of enoxaparin during 14 days. They will receive two injections per day, one of them being a placebo.
Drug: Enoxaparin standard dose

In the control group, patients will receive 1 injection of enoxaparin 4000 IU and 1 injection of placebo until day 14 or hospital discharge in the same form as enoxaparin (subcutaneous injection).

A placebo injection is administered as needed to maintain blinding and ensure the same number of injections as in the intermediate-dose arm.
Experimental: Intermediate Dose LMWH
Patients in the experimental group receive a intermediate dose of enoxparin. They receive two injections of enoxaparin per day.
Drug: Enoxaparin intermediate dose
In the experimental group, patients will receive 2 injections of enoxaparin 4000 IU until day 14 or hospital discharge.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite of symptomatic deep vein thrombosis (DVT), proximal DVT, pulmonary embolism (PE).
Time Frame: Within 14 days following randomisation after severe trauma
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).
Within 14 days following randomisation after severe trauma

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: Within 14 days following randomisation
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
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
Time Frame: Within 14 days following randomisation
  • 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
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
Time Frame: During or within 48h of the last dose of study drug
Major or clinically relevant non-major bleeding, as per ISTH definition, occurring during or within 48h of the last dose of study drug
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)
Time Frame: Within 14 days following randomisation (or until hospital discharge)
Number of red blood cell transfusions within 14 days following randomisation after severe trauma (or until hospital discharge)
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
Time Frame: At day 30 following randomisation
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
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
Time Frame: At day 30 following randomisation
Death at day 30 following randomisation after trauma
At day 30 following randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Grenoble

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alexandre GODON, Chu Grenoble Alpes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 38RC23.0261
  • 2025-522832-16-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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