Comparison of Two Doses of Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients

Phase 3

Completed

• Conditions: Covid19
• Interventions: Drug: Enoxaparin

• Registration Number: NCT04366960
• Lead Sponsor: Niguarda Hospital

Brief Summary

The purpose of this study is to determine whether a higher dose of low molecular weight heparin (enoxaparin 40 mg b.i.d.) is superior than the standard prophylaxis dose (enoxaparin 40 mg o.d.) in reducing thromboembolic events in COVID-19 patients.

Detailed Description

Coronavirus disease-19 (COVID-19 ), which is caused by SARS-CoV-2 infection, are apparently at high risk of venous thromboembolism (VTE), as a consequence of activation of the hemostatic system which, in the most severe cases, can also be associated with the formation of microthrombi and clinically relevant disseminated intravascular coagulation. Concerns about the efficacy of thromboprophylaxis with standard doses of low-molecular-weight heparin (LMWH) has been raised. Therefore, LMWH at higher doses than those recommended for thromboprophylaxis is used in some hospitals, although no evidence exists yet of higher efficacy of high doses compared to standard prophylactic doses. This practice might as well increase the risk of major bleeding. The investigators designed a randomized trial comparing standard prophylactic dose of subcutaneous enoxaparin (40 mg o.d.) with higher dose (40 mg b.i.d) with the aim of testing whether high-dose thromboprophylaxis is more effective than standard dose in preventing VTE in COVID-19 patients.

Study Timeline

• Study First Submitted: 2020-04-24
• Study First Submitted QC: 2020-04-27
• Study First Posted: 2020-04-29
• Study Start: 2020-05-14
• Primary Completion: 2021-05-25
• Study Completion: 2021-05-25
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-07
• Last Update Posted: 2021-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

• All-comers patients aged >=18 years and admitted to hospital with laboratory-confirmed SARS-CoV-2 infection

Exclusion Criteria

• Patients admitted directly to an intensive care unit;
• Estimated creatinine clearance <15 ml/min/1.73m2;
• Patients needing anticoagulant for prior indication;
• Participants involved in other clinical trials;
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
40 mg subcutaneous enoxaparin o.d.	Enoxaparin	Effects of 40 mg subcutaneous enoxaparin o.d.
40 mg subcutaneous enoxaparin b.i.d	Enoxaparin	Effects of 40 mg subcutaneous enoxaparin b.i.d

Primary Outcome Measures

Name	Time	Method
Incidence of venous thromboembolism detected by imaging	30 days	Deep vein thrombosis events diagnosed by serial compression ultrasonography and pulmonary embolism events diagnosed by computed tomography scan

Secondary Outcome Measures

Name	Time	Method
Number of deep venous thrombosis events	30 days	Deep venous thrombosis events diagnosed by serial compression ultrasonography
D-dimer	30 days	To D-dimer compare levels as % above the upper reference limit \[URL\]) among the two groups.
Number of pulmonary embolism events	30 days	Pulmonary embolism events diagnosed by computed tomography scan
Sequential organ failure assessment	30 days	Maximum sequential organ failure assessment (SOFA) score comparison between the two groups.; The SOFA score ranges from 0 to 24. Higher SOFA score is associated with a greater risk of death or prolonged intensive care unit stay.
C-reactive protein	30 days	To compare C-reactive protein levels as % above the upper reference limit \[URL\]) among the two groups.
Interleukin-6	30 days	To compare Interleukin-6 levels as % above the upper reference limit \[URL\]) among the two groups.
In hospital major complications	30 days	death, venous thromboembolism, use of mechanical ventilation, stroke, acute myocardial infarction and admission to an intensive care
hs-troponin levels	30 days	To compare hs-troponin levels as % above the upper reference limit \[URL\]) among the two groups.
Hospital stay	30 days	To compare length of hospital stay between the two groups.
Right ventricular function	30 days	To compare measures of right ventricular function at trans-thoracic echocardiography or CT between admission and follow-up, whenever available
Acute Respiratory Distress Syndrome	30 days	To compare the incidence of SARS-CoV-2-related Acute Respiratory Distress Syndrome (ARDS) between the two groups.

Trial Locations

Locations (1)

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy