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Severe Trauma PatientHEPTRAUMANCT07506473

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

A study testing Enoxaparin standard dose and Enoxaparin intermediate dose in people with Severe Trauma Patient and Venous Thromboembolism, run by University Hospital, Grenoble at 17 sites in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Severe Trauma Patient, Venous Thromboembolism
What is being tested?
Enoxaparin standard dose and Enoxaparin intermediate dose
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
540 participants
Where
17 sitesFrance
Study dates
Apr 2026to May 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • Protected person (art. L1121-5 to L1121-8 of the CSP or art. 31 to 35 of European regulation 536/2014)

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

17 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Alexandre GODON contact

+33 4 76 76 75 75

agodon1@chu-grenoble.fr

Juliana BENY contact

+33 4 76 76 79 55

JBeny@chu-grenoble.fr

17 sites in 1 country

France17 sites

  • CHU Angers

    Angers, 49100

    Sigismond LASOCKI, +33 2 41 35 36 35, silasocki@chu-angers.fr

    Sigismond LASOCKI

  • CHU Clermont Ferrand

    Clermont-Ferrand, 63000

    Benjamin RIEU, +33 4 73 75 41 56, brieu@chu-clermontferrand.fr

    Benjamin RIEU

  • Hôpital Beaujon AP-HP

    Clichy, 92110

    Charles BERNARD, +33 1 40 87 50 81, charles.bernard@aphp.fr

    Charles BERNARD

  • CHU Grenoble Alpes

    Grenoble, 38000

    Alexandre GODON, +33 4 76 76 75 75, agodon1@chu-grenoble.fr

    Juliana BENY, +33 4 76 76 79 55, JBeny@chu-grenoble.fr

  • AP-HP Bicêtre

    Le Kremlin-Bicêtre, 94270

    Inaame ETTOUMI, +33 1 45 21 25 44, inaame.ettoumi@aphp.fr

    Inaame ETTOUMI

  • CHRU Lille

    Lille, 59000

    Delphine GARRIGUE, +33 3 62 94 36 00, delphine.garrigue@chru-lille.fr

    Delphine GARRIGUE

  • Hôpital Edouard Herriot HCL

    Lyon, 69003

    Anne-Claire LUKASZEWICZ, +33 4 72 11 96 86, anne-claire.lukaszewicz@chu-lyon.fr

    Anne-Claire LUKASZEWICZ

  • HCL Lyon Sud

    Lyon, 69310

    Jean Stéphane DAVID, +33 4 78 86 41 40, jean-stephane.david@chu-lyon.fr

    Jean Stéphane DAVID

  • Assistance Publique - Hôpitaux de Marseille

    Marseille, 13005

    Gary DUCLOS, +33 4 91 96 55 31, GARY.DUCLOS@ap-hm.fr

    Gary DUCLOS

  • CHU Montpellier

    Montpellier, 34080

    Pauline DERAS, +33 4 67 33 82 57, p-deras@chu-montpellier.fr

    Pauline DERAS

  • CHU Nantes

    Nantes, 44000

    Yannick HOURMANT, +33 2 40 08 73 80, yannick.hourmant@chu-nantes.fr

    Yannick HOURMANT

  • Hôpital Pitié-Salpêtrière APHP

    Paris, 75013

    Pauline GLASMAN, +33 1 84 82 71 17, pauline.glasman@aphp.fr

    Pauline GLASMAN

  • Hôpital Européen Georges Pompidou AP-HP

    Paris, 75015

    Anne GODIER, +33 1 56 09 25 84, anne.godier@aphp.fr

    Anne GODIER

  • CHU Rennes

    Rennes, 35000

    Yoann LAUNEY, +33 2 99 28 24 22, yoann.launey@chu-rennes.fr

    Yoann LAUNEY

  • CHU Strasbourg

    Strasbourg, 67200

    Julien POTTECHER, +33 3 88 12 70 95, julien.pottecher@chru-strasbourg.fr

    Julien POTTECHER

  • CHU de Toulouse

    Toulouse, 31300

    Véronique ROMANDA, +33 6 43 56 44 07, ramonda.v@chu-toulouse.fr

    Véronique ROMANDA

  • CHU Tours

    Tours, 37000

Other trials in France

About this study

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

Read more

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.

Being tested
Enoxaparin standard dose, Enoxaparin intermediate dose
Keywords
Thromboprophylaxis, Severe trauma, Anticoagulant
Medical subject headings
Venous Thromboembolism, Wounds and Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Enoxaparin standard doseDrug

    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.

  • Enoxaparin intermediate doseDrug

    In the experimental group, patients will receive 2 injections of enoxaparin 4000 IU until day 14 or hospital discharge.

Study groups in NCT07506473
Study groupRoleWhat they receive
Standard Dose LMWHActive comparatorPatients 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.
Receives: Drug: Enoxaparin standard dose
Intermediate Dose LMWHExperimentalPatients in the experimental group receive a intermediate dose of enoxparin. They receive two injections of enoxaparin per day.
Receives: Drug: Enoxaparin intermediate dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Within 14 days following randomisation after severe trauma

Secondary outcomes (6)

  1. 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

    Measured: Within 14 days following randomisation

  2. 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

    Measured: Within 14 days following randomisation

  3. 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

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

  4. 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)

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

  5. 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

    Measured: At day 30 following randomisation

  6. 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

    Measured: At day 30 following randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2026
  2. Study startApr 2026 (estimated)
  3. Primary completionMay 2028 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
540 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07506473
Sponsor's protocol ID
38RC23.0261
Other IDs
2025-522832-16-00, 2025
Acronym
HEPTRAUMA
Status last verified
Apr 2026
First submitted
26 Mar 2026
Last updated
29 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Laporte S, Chapelle C, Bertoletti L, Lega JC, Cucherat M, Zufferey PJ, Darmon JY, Mismetti P; META-EMBOL Group. Indirect comparison meta-analysis of two enoxaparin regimens in patients undergoing major orthopaedic surgery. Impact on the interpretation of thromboprophylactic effects of new anticoagulant drugs. Thromb Haemost. 2014 Sep 2;112(3):503-10. doi: 10.1160/TH14-01-0064. Epub 2014 Jun 26.

    PubMed 24965841

  • Grange L, Chapelle C, Ollier E, Zufferey PJ, Douillet D, Killian M, Mismett P, Laporte S. Adjusted versus fixed doses of LMWHs in trauma patients: A systematic review and meta-analysis. Anaesth Crit Care Pain Med. 2022 Dec;41(6):101155. doi: 10.1016/j.accpm.2022.101155. Epub 2022 Sep 7.

    PubMed 36087698

  • Harrington D, D'Agostino RB Sr, Gatsonis C, Hogan JW, Hunter DJ, Normand ST, Drazen JM, Hamel MB. New Guidelines for Statistical Reporting in the Journal. N Engl J Med. 2019 Jul 18;381(3):285-286. doi: 10.1056/NEJMe1906559. No abstract available.

    PubMed 31314974

  • Klok FA, Ageno W, Barco S, Binder H, Brenner B, Duerschmied D, Empen K, Faggiano P, Ficker JH, Galie N, Ghuysen A, Held M, Heydenreich N, Huisman MV, Jimenez D, Kozak M, Lang IM, Lankeit M, Munzel T, Petris A, Pruszczyk P, Quitzau K, Schellong S, Schmidt KH, Stefanovic BS, Verschuren F, Wolf-Puetz A, Meyer G, Konstantinides SV; PEITHO-2 Investigators. Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study. Thromb Haemost. 2017 Dec;117(12):2425-2434. doi: 10.1160/TH17-06-0434. Epub 2017 Dec 6.

    PubMed 29212130

  • Mantz J, Samama CM, Tubach F, Devereaux PJ, Collet JP, Albaladejo P, Cholley B, Nizard R, Barre J, Piriou V, Poirier N, Mignon A, Schlumberger S, Longrois D, Aubrun F, Farese ME, Ravaud P, Steg PG; Stratagem Study Group. Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial. Br J Anaesth. 2011 Dec;107(6):899-910. doi: 10.1093/bja/aer274. Epub 2011 Aug 27.

    PubMed 21873632

  • Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ni Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. No abstract available.

    PubMed 31504429

  • Bouzat P, Bosson JL, David JS, Riou B, Duranteau J, Payen JF; PROCOAG study group. Four-factor prothrombin complex concentrate to reduce allogenic blood product transfusion in patients with major trauma, the PROCOAG trial: study protocol for a randomized multicenter double-blind superiority study. Trials. 2021 Sep 16;22(1):634. doi: 10.1186/s13063-021-05524-x.

    PubMed 34530886

  • Gauss T, Bouzat P, Geeraerts T. Epidemiology of trauma: From medico-administrative database to large prospective registry. Anaesth Crit Care Pain Med. 2019 Oct;38(5):439-440. doi: 10.1016/j.accpm.2019.08.001. No abstract available.

    PubMed 31585763

  • Gauss T, Balandraud P, Frandon J, Abba J, Ageron FX, Albaladejo P, Arvieux C, Barbois S, Bijok B, Bobbia X, Charbit J, Cook F, David JS, Maurice GS, Duranteau J, Garrigue D, Gay E, Geeraerts T, Ghelfi J, Hamada S, Harrois A, Kobeiter H, Leone M, Levrat A, Mirek S, Nadji A, Paugam-Burtz C, Payen JF, Perbet S, Pirracchio R, Plenier I, Pottecher J, Rigal S, Riou B, Savary D, Secheresse T, Tazarourte K, Thony F, Tonetti J, Tresallet C, Wey PF, Picard J, Bouzat P; Groupe d'interet en traumatologie grave (GITE). Strategic proposal for a national trauma system in France. Anaesth Crit Care Pain Med. 2019 Apr;38(2):121-130. doi: 10.1016/j.accpm.2018.05.005. Epub 2018 May 29.

    PubMed 29857186

  • Godon A, Gabin M, Levy JH, Huet O, Chapalain X, David JS, Tacquard C, Sattler L, Minville V, Memier V, Blanie A, Godet T, Leone M, De Maistre E, Gruel Y, Roullet S, Vermorel C, Samama CM, Bosson JL, Albaladejo P; GIHP-NACO Study Group. Management of urgent invasive procedures in patients treated with direct oral anticoagulants: An observational registry analysis. Thromb Res. 2022 Aug;216:106-112. doi: 10.1016/j.thromres.2022.06.005. Epub 2022 Jun 22.

    PubMed 35785621

  • Prieto-Merino D, Smeeth L, Staa TP, Roberts I. Dangers of non-specific composite outcome measures in clinical trials. BMJ. 2013 Nov 22;347:f6782. doi: 10.1136/bmj.f6782. No abstract available.

    PubMed 24270506

  • Spyropoulos AC, Goldin M, Giannis D, Diab W, Wang J, Khanijo S, Mignatti A, Gianos E, Cohen M, Sharifova G, Lund JM, Tafur A, Lewis PA, Cohoon KP, Rahman H, Sison CP, Lesser ML, Ochani K, Agrawal N, Hsia J, Anderson VE, Bonaca M, Halperin JL, Weitz JI; HEP-COVID Investigators. Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial. JAMA Intern Med. 2021 Dec 1;181(12):1612-1620. doi: 10.1001/jamainternmed.2021.6203.

    PubMed 34617959

  • Ho KM, Rao S, Honeybul S, Zellweger R, Wibrow B, Lipman J, Holley A, Kop A, Geelhoed E, Corcoran T, Misur P, Edibam C, Baker RI, Chamberlain J, Forsdyke C, Rogers FB. A Multicenter Trial of Vena Cava Filters in Severely Injured Patients. N Engl J Med. 2019 Jul 25;381(4):328-337. doi: 10.1056/NEJMoa1806515. Epub 2019 Jul 7.

    PubMed 31259488

  • Samama CM, Laporte S, Rosencher N, Girard P, Llau J, Mouret P, Fisher W, Martinez-Martin J, Duverger D, Deygas B, Presles E, Cucherat M, Mismetti P; PRONOMOS Investigators. Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery. N Engl J Med. 2020 May 14;382(20):1916-1925. doi: 10.1056/NEJMoa1913808. Epub 2020 Mar 29.

    PubMed 32223113

  • Riou B, Rothmann C, Lecoules N, Bouvat E, Bosson JL, Ravaud P, Samama CM, Hamadouche M. Incidence and risk factors for venous thromboembolism in patients with nonsurgical isolated lower limb injuries. Am J Emerg Med. 2007 Jun;25(5):502-8. doi: 10.1016/j.ajem.2006.09.012.

    PubMed 17543652

Questions about this trial

What is this clinical trial studying?

A study testing Enoxaparin standard dose and Enoxaparin intermediate dose in people with Severe Trauma Patient and Venous Thromboembolism, run by University Hospital, Grenoble at 17 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Alexandre GODON (+33 4 76 76 75 75, agodon1@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of symptomatic deep vein thrombosis (DVT), proximal DVT, pulmonary embolism (PE). (time frame: Within 14 days following randomisation after severe trauma). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07506473, which also lists 44 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.

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