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

NCT07506473 | Not Yet Recruiting DMC

• 2 other identifiers: 38RC23.02612025-522832-16-00
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 17

Brief 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. 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.

Conditions

Severe Trauma Patient; Venous Thromboembolism

Keywords

Thromboprophylaxis; Severe trauma; Anticoagulant

Outcome Measures

Primary Outcomes (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).

  Within 14 days following randomisation after severe trauma

Secondary Outcomes (6)

• 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

  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

  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

  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)

  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

  At day 30 following randomisation

Study Arms (2)

Standard Dose LMWH

ACTIVE COMPARATOR

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

Intermediate Dose LMWH

EXPERIMENTAL

Patients in the experimental group receive a intermediate dose of enoxparin. They receive two injections of enoxaparin per day.

Drug: Enoxaparin intermediate dose

Interventions

Enoxaparin standard dose DRUG

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.

Standard Dose LMWH

Enoxaparin intermediate dose DRUG

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

Intermediate Dose LMWH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (17)

CHU Angers

Angers, 49100, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

Hôpital Beaujon AP-HP

Clichy, 92110, France

Location

CHU Grenoble Alpes

Grenoble, 38000, France

Location

AP-HP Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

CHRU Lille

Lille, 59000, France

Location

Hôpital Edouard Herriot HCL

Lyon, 69003, France

Location

HCL Lyon Sud

Lyon, 69310, France

Location

Assistance Publique - Hôpitaux de Marseille

Marseille, 13005, France

Location

CHU Montpellier

Montpellier, 34080, France

Location

CHU Nantes

Nantes, 44000, France

Location

Hôpital Pitié-Salpêtrière APHP

Paris, 75013, France

Location

Hôpital Européen Georges Pompidou AP-HP

Paris, 75015, France

Location

CHU Rennes

Rennes, 35000, France

Location

CHU Strasbourg

Strasbourg, 67200, France

Location

CHU de Toulouse

Toulouse, 31300, France

Location

CHU Tours

Tours, 37000, France

Location

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• 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.

  PMID: 24965841 BACKGROUND

• 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.

  PMID: 36087698 BACKGROUND

• 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.

  PMID: 31314974 BACKGROUND

• 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.

  PMID: 29212130 BACKGROUND

• 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.

  PMID: 21873632 BACKGROUND

• 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.

  PMID: 31504429 BACKGROUND

• 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.

  PMID: 34530886 BACKGROUND

• 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.

  PMID: 31585763 BACKGROUND

• 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.

  PMID: 29857186 BACKGROUND

• 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.

  PMID: 35785621 BACKGROUND

• 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.

  PMID: 24270506 BACKGROUND

• 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. Erratum In: JAMA Intern Med. 2022 Feb 1;182(2):239. doi: 10.1001/jamainternmed.2021.7668.

  PMID: 34617959 BACKGROUND

• 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.

  PMID: 31259488 BACKGROUND

• 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.

  PMID: 32223113 BACKGROUND

• 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.

  PMID: 17543652 BACKGROUND

• Smythe MA, Koerber JM, Mattson JC. The incidence of recognized heparin-induced thrombocytopenia in a large, tertiary care teaching hospital. Chest. 2007 Jun;131(6):1644-9. doi: 10.1378/chest.06-2109. Epub 2007 Mar 30.

  PMID: 17400685 BACKGROUND

• Rodier SG, Kim M, Moore S, Frangos SG, Tandon M, Klein MJ, Berry CD, Huang PP, DiMaggio CJ, Bukur M. Early Anti-Xa Assay-Guided Low Molecular Weight Heparin Chemoprophylaxis Is Safe in Adult Patients with Acute Traumatic Brain Injury. Am Surg. 2020 Apr 1;86(4):369-376.

  PMID: 32391762 BACKGROUND

• Tavoly M, Asady E, Wik HS, Ghanima W. Measuring Quality of Life after Venous Thromboembolism: Who, When, and How? Semin Thromb Hemost. 2023 Nov;49(8):861-866. doi: 10.1055/s-0042-1754390. Epub 2022 Sep 2.

  PMID: 36055276 BACKGROUND

• Bonnefoy PB, Margelidon-Cozzolino V, Catella-Chatron J, Ayoub E, Guichard JB, Murgier M, Bertoletti L. What's next after the clot? Residual pulmonary vascular obstruction after pulmonary embolism: From imaging finding to clinical consequences. Thromb Res. 2019 Dec;184:67-76. doi: 10.1016/j.thromres.2019.09.038. Epub 2019 Oct 28.

  PMID: 31710860 BACKGROUND

• Ratnasekera A, Geerts W, Haut ER, Price M, Costantini T, Murphy P. Implementation science approaches to optimizing venous thromboembolism prevention in patients with traumatic injuries: Findings from the 2022 Consensus Conference to Implement Optimal Venous Thromboembolism Prophylaxis in Trauma. J Trauma Acute Care Surg. 2023 Mar 1;94(3):490-494. doi: 10.1097/TA.0000000000003850. Epub 2022 Dec 6.

  PMID: 36729882 BACKGROUND

• Hollestelle MJ, van der Meer FJM, Meijer P. Quality performance for indirect Xa inhibitor monitoring in patients using international external quality data. Clin Chem Lab Med. 2020 Oct 25;58(11):1921-1930. doi: 10.1515/cclm-2020-0130.

  PMID: 32441664 BACKGROUND

• Verhoeff K, Raffael K, Connell M, Kung JY, Strickland M, Parker A, Anantha RV. Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis. J Trauma Acute Care Surg. 2022 Aug 1;93(2):e61-e70. doi: 10.1097/TA.0000000000003580. Epub 2022 Feb 22.

  PMID: 35195094 BACKGROUND

• Tran A, Fernando SM, Gates RS, Gillen JR, Droege ME, Carrier M, Inaba K, Haut ER, Cotton B, Teichman A, Engels PT, Patel RV, Lampron J, Rochwerg B. Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis. Ann Surg. 2023 May 1;277(5):734-741. doi: 10.1097/SLA.0000000000005754. Epub 2022 Nov 22.

  PMID: 36413031 BACKGROUND

• Karcutskie CA, Dharmaraja A, Patel J, Eidelson SA, Padiadpu AB, Martin AG, Lama G, Lineen EB, Namias N, Schulman CI, Proctor KG. Association of Anti-Factor Xa-Guided Dosing of Enoxaparin With Venous Thromboembolism After Trauma. JAMA Surg. 2018 Feb 1;153(2):144-149. doi: 10.1001/jamasurg.2017.3787.

  PMID: 29071333 BACKGROUND

• Ley EJ, Brown CVR, Moore EE, Sava JA, Peck K, Ciesla DJ, Sperry JL, Rizzo AG, Rosen NG, Brasel KJ, Kozar R, Inaba K, Martin MJ. Updated guidelines to reduce venous thromboembolism in trauma patients: A Western Trauma Association critical decisions algorithm. J Trauma Acute Care Surg. 2020 Nov;89(5):971-981. doi: 10.1097/TA.0000000000002830. No abstract available.

  PMID: 32590563 BACKGROUND

• Bistervels IM, Buchmuller A, Wiegers HMG, Ni Ainle F, Tardy B, Donnelly J, Verhamme P, Jacobsen AF, Hansen AT, Rodger MA, DeSancho MT, Shmakov RG, van Es N, Prins MH, Chauleur C, Middeldorp S; Highlow Block writing committee; Highlow Investigators. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet. 2022 Nov 19;400(10365):1777-1787. doi: 10.1016/S0140-6736(22)02128-6. Epub 2022 Oct 28.

  PMID: 36354038 BACKGROUND

• INSPIRATION Investigators; Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, Farrokhpour M, Sezavar SH, Payandemehr P, Dabbagh A, Moghadam KG, Jamalkhani S, Khalili H, Yadollahzadeh M, Riahi T, Rezaeifar P, Tahamtan O, Matin S, Abedini A, Lookzadeh S, Rahmani H, Zoghi E, Mohammadi K, Sadeghipour P, Abri H, Tabrizi S, Mousavian SM, Shahmirzaei S, Bakhshandeh H, Amin A, Rafiee F, Baghizadeh E, Mohebbi B, Parhizgar SE, Aliannejad R, Eslami V, Kashefizadeh A, Kakavand H, Hosseini SH, Shafaghi S, Ghazi SF, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Piazza G, Kirtane AJ, Van Tassell BW, Dobesh PP, Stone GW, Lip GYH, Krumholz HM, Goldhaber SZ, Bikdeli B. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Apr 27;325(16):1620-1630. doi: 10.1001/jama.2021.4152.

  PMID: 33734299 BACKGROUND

• Song JQ, Xuan LZ, Wu W, Huang JF, Zhong M. Low molecular weight heparin once versus twice for thromboprophylaxis following esophagectomy: a randomised, double-blind and placebo-controlled trial. J Thorac Dis. 2015 Jul;7(7):1158-64. doi: 10.3978/j.issn.2072-1439.2015.06.15.

  PMID: 26380731 BACKGROUND

• Wang TF, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014 Jan;111(1):88-93. doi: 10.1160/TH13-01-0042. Epub 2013 Oct 17.

  PMID: 24136071 BACKGROUND

• Droege ME, Mueller EW, Besl KM, Lemmink JA, Kramer EA, Athota KP, Droege CA, Ernst NE, Keegan SP, Lutomski DM, Hanseman DJ, Robinson BR. Effect of a dalteparin prophylaxis protocol using anti-factor Xa concentrations on venous thromboembolism in high-risk trauma patients. J Trauma Acute Care Surg. 2014 Feb;76(2):450-6. doi: 10.1097/TA.0000000000000087.

  PMID: 24458050 BACKGROUND

• Ko A, Harada MY, Barmparas G, Chung K, Mason R, Yim DA, Dhillon N, Margulies DR, Gewertz BL, Ley EJ. Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma. JAMA Surg. 2016 Nov 1;151(11):1006-1013. doi: 10.1001/jamasurg.2016.1662.

  PMID: 27383732 BACKGROUND

• Haentjens P. Thromboembolic prophylaxis in orthopaedic trauma patients: a comparison between a fixed dose and an individually adjusted dose of a low molecular weight heparin (nadroparin calcium). Injury. 1996 Jul;27(6):385-90. doi: 10.1016/0020-1383(96)00042-3.

  PMID: 8881132 BACKGROUND

• Kay AB, Majercik S, Sorensen J, Woller SC, Stevens SM, White TW, Morris DS, Baldwin M, Bledsoe JR. Weight-based enoxaparin dosing and deep vein thrombosis in hospitalized trauma patients: A double-blind, randomized, pilot study. Surgery. 2018 Apr 23:S0039-6060(18)30094-1. doi: 10.1016/j.surg.2018.03.001. Online ahead of print.

  PMID: 29699807 BACKGROUND

• Samama CM, Boubli L, Coloby P, Debourdeau P, Gruel Y, Mariette C, Mottier D, Rischmann P, Toubiana L, Steib A. Venous thromboembolism prophylaxis in patients undergoing abdominal or pelvic surgery for cancer--a real-world, prospective, observational French study: PReOBS. Thromb Res. 2014 Jun;133(6):985-92. doi: 10.1016/j.thromres.2013.10.038. Epub 2013 Nov 1.

  PMID: 24231117 BACKGROUND

• CRISTAL Study Group; Sidhu VS, Kelly TL, Pratt N, Graves SE, Buchbinder R, Adie S, Cashman K, Ackerman I, Bastiras D, Brighton R, Burns AWR, Chong BH, Clavisi O, Cripps M, Dekkers M, de Steiger R, Dixon M, Ellis A, Griffith EC, Hale D, Hansen A, Harris A, Hau R, Horsley M, James D, Khorshid O, Kuo L, Lewis P, Lieu D, Lorimer M, MacDessi S, McCombe P, McDougall C, Mulford J, Naylor JM, Page RS, Radovanovic J, Solomon M, Sorial R, Summersell P, Tran P, Walter WL, Webb S, Wilson C, Wysocki D, Harris IA. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial. JAMA. 2022 Aug 23;328(8):719-727. doi: 10.1001/jama.2022.13416.

  PMID: 35997730 BACKGROUND

• Major Extremity Trauma Research Consortium (METRC); O'Toole RV, Stein DM, O'Hara NN, Frey KP, Taylor TJ, Scharfstein DO, Carlini AR, Sudini K, Degani Y, Slobogean GP, Haut ER, Obremskey W, Firoozabadi R, Bosse MJ, Goldhaber SZ, Marvel D, Castillo RC. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med. 2023 Jan 19;388(3):203-213. doi: 10.1056/NEJMoa2205973.

  PMID: 36652352 BACKGROUND

• Hamada SR, Espina C, Guedj T, Buaron R, Harrois A, Figueiredo S, Duranteau J. High level of venous thromboembolism in critically ill trauma patients despite early and well-driven thromboprophylaxis protocol. Ann Intensive Care. 2017 Sep 12;7(1):97. doi: 10.1186/s13613-017-0315-0.

  PMID: 28900890 BACKGROUND

• Stein AL, Rossler J, Braun J, Sprengel K, Beeler PE, Spahn DR, Kaserer A, Stein P. Impact of a goal-directed factor-based coagulation management on thromboembolic events following major trauma. Scand J Trauma Resusc Emerg Med. 2019 Dec 30;27(1):117. doi: 10.1186/s13049-019-0697-0.

  PMID: 31888722 BACKGROUND

• Sumislawski JJ, Kornblith LZ, Conroy AS, Callcut RA, Cohen MJ. Dynamic coagulability after injury: Is delaying venous thromboembolism chemoprophylaxis worth the wait? J Trauma Acute Care Surg. 2018 Nov;85(5):907-914. doi: 10.1097/TA.0000000000002048.

  PMID: 30124623 BACKGROUND

• Perissier C, Crespy T, Godon A, Bosson JL, Bouzat P. Reasons for a late initiation of pharmacological thromboprophylaxis in severe trauma patients: A prospective observational study. Anaesth Crit Care Pain Med. 2022 Apr;41(2):101037. doi: 10.1016/j.accpm.2022.101037. Epub 2022 Feb 19. No abstract available.

  PMID: 35189398 BACKGROUND

• Duranteau J, Taccone FS, Verhamme P, Ageno W; ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis: Intensive care. Eur J Anaesthesiol. 2018 Feb;35(2):142-146. doi: 10.1097/EJA.0000000000000707.

  PMID: 29112545 BACKGROUND

• Samama CM, Gafsou B, Jeandel T, Laporte S, Steib A, Marret E, Albaladejo P, Mismetti P, Rosencher N; French Society of Anaesthesia and Intensive Care. [French Society of Anaesthesia and Intensive Care. Guidelines on perioperative venous thromboembolism prophylaxis. Update 2011. Short text]. Ann Fr Anesth Reanim. 2011 Dec;30(12):947-51. doi: 10.1016/j.annfar.2011.10.008. Epub 2011 Nov 21. No abstract available. French.

  PMID: 22104443 BACKGROUND

• Ho KM, Burrell M, Rao S, Baker R. Incidence and risk factors for fatal pulmonary embolism after major trauma: a nested cohort study. Br J Anaesth. 2010 Nov;105(5):596-602. doi: 10.1093/bja/aeq254. Epub 2010 Sep 22.

  PMID: 20861095 BACKGROUND

• Thorson CM, Ryan ML, Van Haren RM, Curia E, Barrera JM, Guarch GA, Busko AM, Namias N, Livingstone AS, Proctor KG. Venous thromboembolism after trauma: a never event?*. Crit Care Med. 2012 Nov;40(11):2967-73. doi: 10.1097/CCM.0b013e31825bcb60.

  PMID: 22890248 BACKGROUND

MeSH Terms

Conditions

Venous Thromboembolism; Wounds and Injuries

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Alexandre GODON

  CHU Grenoble Alpes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 1, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (17)