Low-molecular-weight heparin to prevent venous thromboembolism in COVID-19 patients : a randomized controlled trial of different doses

Effectiveness of low molecular weight heparin at increased doses prophylaxis weight-adjusted, compared with lower doses prophylaxis (intermediate or standard), on the onset of venous thromboembolism in coronavirus disease 2019 (COVID-19) hospitalized patients : The randomized multicentric controlled open-label trial COVI-DOSE

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-001709-21-FR

Enrollment

550

Registered

2020-04-16

Start date

2020-04-29

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prevention of thromboembolic events in hospitalised COVID-19 infected patients MedDRA version: 20.0 Level: HLGT Classification code 10014523 Term: Embolism and thrombosis System Organ Class: 10047065 - Vascular disorders

Interventions

Trade Name: Enoxaparin (LOVENOX or other specialties) Product Name: Enoxaparin (Low Molecular Weight Heparin) Pharmaceutical Form: Injection INN or Proposed INN: enoxaparin CAS Number: 9005-49-6 Other

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Adult - Having been given an informed consent to participate or consent from relatives in case of vital emergency (patients not able to give a consent) -Hospitalization for a acute respiratory COVID-19 infection probable or confirmed -SARS-Cov-2 infection diagnosed by biology (positive PCR for COVID-19 on a nasophayngeal swab or any other saple and/or serological method) or by a composite criterium associating lung injury on imaging and clinical / biological symptoms suggestive of COVID-19 (eg : dyspnea, cough, fever, biological inflammatory syndrome, lymphopenia, elevated liver enzymes). - Health Insurance Coverage Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 230 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 320

Exclusion criteria

Exclusion criteria: -End-stage kidney disease (glomerular filtration rate 180 mmHg) or diastolic (> 110 mmHg) hypertension during more than 12 hours or needing an intravenous treatment, recent (2N ou ACT>2N), thrombocytopenia < 75 G/L, heparin-induced thrombocytopenia, contraindication to blood-derived products -Lower limb Venous Doppler ultrasound not feasible (bilateral transfemoral amputation, or severe burns) - Death expected within 48 hours - Persons referred in articles L.1121-5 to L.1121-8 and L.1122-2 of the Public Health Code: o Pregnant, parturient or breastfeeding woman; o Person deprived of liberty for judicial or administrative decision; o Person under psychiatric care; o Minor person (non-emancipated); o Adult person under legal protection (any form of public guardianship).

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the effectiveness, during the hospitalization, of low molecular weight heparin at increased doses prophylaxis weight-adjusted, compared with lower doses prophylaxis (intermediate or standard), on the onset of venous thromboembolism, causing death or not, in coronavirus 19 patients hospitalized in medical care units or intensive care units;Secondary Objective: To evaluate the effectiveness of a weight-ajusted increased prophylactic dose of low molecular weight heparin, compared with a lower prophylactic dose, on : 1a. Major bleeding, 1b. Major and clinical relevant non-major bleeding, 2. Net clinical benefit corresponding to the association of venous thromboembolism and major bleeding 3a. Venous thrombosis at other sites than the primary outcome, 3b. Symptomatic arterial thrombosis 4. All-cause mortality 5. Primary outcome in predefined sub-groups (eg. renal function) 6. To identify variables associated with the risk of venous thromboembolism ;Primary end point(s): The primary endpoint is the onset of a symptomatic venous thromboembolic event, during the hospitalization stay (and limited to D28 of hospitalization), as defined by a: - Symptomatic deep venous thrombosis, whatever the site and confirmed by a compression ultrasonography or an abnormal computed tomography angiogram with venous opacification or - Symptomatic pulmonary embolism, confirmed by: • a computed tomography angiogram, • or a V/Q scan, • or the presence, in a patient with a recent worsening dyspnea, of a deep venous thrombosis and/or a right ventricular dysfonction diagnosed by a transthoracic echocardiography in an unstable patients unable to benefit from a CT angiogram (2019 European Society of Cardiology Guidelines) or - Unexplained death when a pulmonary embolism cannot be excluded. The primary endpoint is a composite measure of clinical events and/or survival, as recommended by the WHO guidelines on COVID-19 Therapeutic Trial Synopsis (february, 2020). For	—

Measure

Time frame

Main Objective: To evaluate the effectiveness, during the hospitalization, of low molecular weight heparin at increased doses prophylaxis weight-adjusted, compared with lower doses prophylaxis (intermediate or standard), on the onset of venous thromboembolism, causing death or not, in coronavirus 19 patients hospitalized in medical care units or intensive care units;Secondary Objective: To evaluate the effectiveness of a weight-ajusted increased prophylactic dose of low molecular weight heparin, compared with a lower prophylactic dose, on : 1a. Major bleeding, 1b. Major and clinical relevant non-major bleeding, 2. Net clinical benefit corresponding to the association of venous thromboembolism and major bleeding 3a. Venous thrombosis at other sites than the primary outcome, 3b. Symptomatic arterial thrombosis 4. All-cause mortality 5. Primary outcome in predefined sub-groups (eg. renal function) 6. To identify variables associated with the risk of venous thromboembolism ;Primary end point(s): The primary endpoint is the onset of a symptomatic venous thromboembolic event, during the hospitalization stay (and limited to D28 of hospitalization), as defined by a: - Symptomatic deep venous thrombosis, whatever the site and confirmed by a compression ultrasonography or an abnormal computed tomography angiogram with venous opacification or - Symptomatic pulmonary embolism, confirmed by: • a computed tomography angiogram, • or a V/Q scan, • or the presence, in a patient with a recent worsening dyspnea, of a deep venous thrombosis and/or a right ventricular dysfonction diagnosed by a transthoracic echocardiography in an unstable patients unable to benefit from a CT angiogram (2019 European Society of Cardiology Guidelines) or - Unexplained death when a pulmonary embolism cannot be excluded. The primary endpoint is a composite measure of clinical events and/or survival, as recommended by the WHO guidelines on COVID-19 Therapeutic Trial Synopsis (february, 2020). For

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Secondary

Measure	Time frame
Secondary end point(s): 1a. The onset of a major bleeding as defined by the International Society on Thrombosis and Haemostasis: • Bleeding causing a fall in hemoglobin level = 2 g/dL or needing a transfusion (whole blood or red cells) = 2 units, and/or • a bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or • fatal bleeding. 2d. The onset of a clinically-relevant non major bleeding as defined by the International Society on Thrombosis and Haemostasis as any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not ?t the criteria for the ISTH de?nition of major bleeding but does meet at least one of the following criteria: • requiring medical intervention by a healthcare professional, and/or • needing a temporary cessation of the study treatment, and/or • causing discomfort for the patient such as pain. The clinically-relevant non major bleeding may be : macroscopic haematuria, gastrointestinal bleeding, hemoptysis, muscle hematoma, spontaneous subcutaneous hematoma > 25 cm2 or provoked subcutaneous hematoma > 100 cm2, multiple source bleeding, hematoma / bleeding from other site. 2. The net clinical benefit defined as composite criterium associating venous thromboembolism and major bleeding 3a. The onset of venous thrombosis at other sites than the primary outcome: • superficial venous thrombosis, and/or • venous central catheter-related thrombosis/PiCC-line/Midline, and/or • thombosis of an extracorporeal dialysis circuit (diagnosed by a dysfunction of the circuit), and/or • thrombosis of an extracorporeal membrane oxygenation (diagnosed by a dysfunction of the circuit) • deep vein thrombosis in other sites (eg. upper limb, splanchnic vein thrombosis, cerebral thrombophlebitis) These thromboses must be confirmed by a referenc	—

Measure

Time frame

Secondary end point(s): 1a. The onset of a major bleeding as defined by the International Society on Thrombosis and Haemostasis: • Bleeding causing a fall in hemoglobin level = 2 g/dL or needing a transfusion (whole blood or red cells) = 2 units, and/or • a bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or • fatal bleeding. 2d. The onset of a clinically-relevant non major bleeding as defined by the International Society on Thrombosis and Haemostasis as any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not ?t the criteria for the ISTH de?nition of major bleeding but does meet at least one of the following criteria: • requiring medical intervention by a healthcare professional, and/or • needing a temporary cessation of the study treatment, and/or • causing discomfort for the patient such as pain. The clinically-relevant non major bleeding may be : macroscopic haematuria, gastrointestinal bleeding, hemoptysis, muscle hematoma, spontaneous subcutaneous hematoma > 25 cm2 or provoked subcutaneous hematoma > 100 cm2, multiple source bleeding, hematoma / bleeding from other site. 2. The net clinical benefit defined as composite criterium associating venous thromboembolism and major bleeding 3a. The onset of venous thrombosis at other sites than the primary outcome: • superficial venous thrombosis, and/or • venous central catheter-related thrombosis/PiCC-line/Midline, and/or • thombosis of an extracorporeal dialysis circuit (diagnosed by a dysfunction of the circuit), and/or • thrombosis of an extracorporeal membrane oxygenation (diagnosed by a dysfunction of the circuit) • deep vein thrombosis in other sites (eg. upper limb, splanchnic vein thrombosis, cerebral thrombophlebitis) These thromboses must be confirmed by a referenc

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Countries

France

Contacts

Public ContactDirection de la Recherche Clinique

CHRU de Nancy

dripromoteur@chru-nancy.fr33383 155285

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026