Comparison of Two Doses of Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients (X-Covid 19)

Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients: Comparison of 40 mg o.d. Versus 40 mg b.i.d. A Randomized Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Enoxaparin

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 Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 40 mg subcutaneous enoxaparin o.d.; Effects of 40 mg subcutaneous enoxaparin o.d.	Drug: Enoxaparin; Subcutaneous enoxaparin
Active Comparator: 40 mg subcutaneous enoxaparin b.i.d; Effects of 40 mg subcutaneous enoxaparin b.i.d	Drug: Enoxaparin; Subcutaneous enoxaparin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In hospital major complications	death, venous thromboembolism, use of mechanical ventilation, stroke, acute myocardial infarction and admission to an intensive care	30 days
Number of deep venous thrombosis events	Deep venous thrombosis events diagnosed by serial compression ultrasonography	30 days
Sequential organ failure assessment	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.	30 days
C-reactive protein	To compare C-reactive protein levels as % above the upper reference limit [URL]) among the two groups.	30 days
Interleukin-6	To compare Interleukin-6 levels as % above the upper reference limit [URL]) among the two groups.	30 days
D-dimer	To D-dimer compare levels as % above the upper reference limit [URL]) among the two groups.	30 days
hs-troponin levels	To compare hs-troponin levels as % above the upper reference limit [URL]) among the two groups.	30 days
Acute Respiratory Distress Syndrome	To compare the incidence of SARS-CoV-2-related Acute Respiratory Distress Syndrome (ARDS) between the two groups.	30 days
Hospital stay	To compare length of hospital stay between the two groups.	30 days
Right ventricular function	To compare measures of right ventricular function at trans-thoracic echocardiography or CT between admission and follow-up, whenever available	30 days
Number of pulmonary embolism events	Pulmonary embolism events diagnosed by computed tomography scan	30 days

Collaborators and Investigators

• Sponsor: Niguarda Hospital

Publications and helpful links

General Publications

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.
• Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9. Epub 2020 May 11. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2020
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): May 25, 2021

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: COVID19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 2020-001708-41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No