Intermediate versus standard dose enoxaparin to prevent venous thromboembolism in severe trauma patients: a multicenter double blind randomised controlled trial (HEPTRAUMA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Grenoble Alpes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Hemic and Lymphatic Diseases [C15], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Decision date (initial)

2025-12-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To determine the effect of intermediate versus standard dose low-molecular-weight heparin on the incidence of major venous thromboembolism following severe trauma.

Secondary objectives 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,
2. To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on the incidence of major bleeding and clinically relevant non-major bleeding as per ISTH definition,
3. To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on the incidence of major venous thromboembolism and major bleeding at day 30 following randomisation after a severe trauma
4. To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on the incidence of deaths at day 30 following randomisation after a severe trauma
5. To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on: - the individual components of the primary outcome
6. To evaluate the effect of intermediate versus standard dose low-molecular-weight heparin on: - the incidence of red blood cell transfusions within 14 days following randomisation after severe trauma (or until hospital discharge)

Conditions and MedDRA coding

Severe trauma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 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
2. Affiliation to the French social security system or European (CEAM)

Exclusion criteria 16

1. Prehospital cardiac arrest
2. Hospital admission >72 hours
3. More than one dose of prophylactic anticoagulant already administered since trauma
4. Renal failure defined by creatinine clearance of 30 mL/min or less (Cockcroft-Gault formula)
5. Body weight >100 kg or <45 kg
6. Indication for therapeutic anticoagulation
7. Major known thrombophilia (e.g. antiphospholipid syndrome, antithrombin deficiency)
8. Constitutional bleeding disorder (haemophilia, von Willebrand disease, coagulation factor deficiency, platelet disorder).
9. Thrombocytopenia inferior to 50 G.L-1
10. History of heparin-induced thrombocytopenia
11. Study drug hypersensitivity
12. Limitation of life support, life expectancy ≤7 days or palliative care
13. 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.)
14. Pregnant or breastfeeding woman
15. Inclusion in another experimental trial
16. Protected person (art. L1121-5 to L1121-8 of the CSP or art. 31 to 35 of European regulation 536/2014)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite of symptomatic deep vein thrombosis, proximal deep vein thrombosis, pulmonary embolism within 14 days following randomisation after severe trauma

Secondary endpoints 2

1. Key secondary endpoint (included in a sequential hierarchical testing procedure): 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
2. Other endpoints: Major or clinically relevant non-major bleeding, as per ISTH definition, occurring during or within 48h of the last dose of study drug; Incidence of major venous thromboembolism (as defined in the primary endpoint) and major bleeding (as per ISTH definition) at day 30 following randomisation; death at day 30 following randomisation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Grenoble Alpes

Sponsor organisation

Centre Hospitalier Universitaire Grenoble Alpes

Address

Boulevard De La Chantourne, Cs 10217, La Tronche Cs 10217 La Tronche

City

Grenoble Cedex 9

Postcode

38043

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

GODON Alexandre

Public contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

GODON Alexandre

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications