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

• ClinicalTrials.gov Identifier: NCT04366960
• Recruitment Status: Completed
• First Posted: April 29, 2020
• Last Update Posted: June 8, 2021
• Sponsor: Niguarda Hospital
• Information provided by (Responsible Party): Niguarda Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: Enoxaparin	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open-label Multicentre Prospective Controlled Randomized Trial in patients with SARS-CoV-2 infection. Patients will be randomized 1:1 to 40 mg subcutaneous enoxaparin o.d. versus 40 mg enoxaparin b.i.d within 12 hours after hospitalization.
• Masking: None (Open Label)
• Masking Description: Open label
• Primary Purpose: Treatment
• Official Title: Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients: Comparison of 40 mg o.d. Versus 40 mg b.i.d. A Randomized Clinical Trial
• Actual Study Start Date: May 14, 2020
• Actual Primary Completion Date: May 25, 2021
• Actual Study Completion Date: May 25, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of venous thromboembolism detected by imaging [ Time Frame: 30 days ]
   Deep vein thrombosis events diagnosed by serial compression ultrasonography and pulmonary embolism events diagnosed by computed tomography scan

Secondary Outcome Measures :

1. In hospital major complications [ Time Frame: 30 days ]
   death, venous thromboembolism, use of mechanical ventilation, stroke, acute myocardial infarction and admission to an intensive care
2. Number of deep venous thrombosis events [ Time Frame: 30 days ]
   Deep venous thrombosis events diagnosed by serial compression ultrasonography
3. Sequential organ failure assessment [ Time Frame: 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.

4. C-reactive protein [ Time Frame: 30 days ]
   To compare C-reactive protein levels as % above the upper reference limit [URL]) among the two groups.
5. Interleukin-6 [ Time Frame: 30 days ]
   To compare Interleukin-6 levels as % above the upper reference limit [URL]) among the two groups.
6. D-dimer [ Time Frame: 30 days ]
   To D-dimer compare levels as % above the upper reference limit [URL]) among the two groups.
7. hs-troponin levels [ Time Frame: 30 days ]
   To compare hs-troponin levels as % above the upper reference limit [URL]) among the two groups.
8. Acute Respiratory Distress Syndrome [ Time Frame: 30 days ]
   To compare the incidence of SARS-CoV-2-related Acute Respiratory Distress Syndrome (ARDS) between the two groups.
9. Hospital stay [ Time Frame: 30 days ]
   To compare length of hospital stay between the two groups.
10. Right ventricular function [ Time Frame: 30 days ]
    To compare measures of right ventricular function at trans-thoracic echocardiography or CT between admission and follow-up, whenever available
11. Number of pulmonary embolism events [ Time Frame: 30 days ]
    Pulmonary embolism events diagnosed by computed tomography scan

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milano, Italy, 20162

Sponsors and Collaborators

Niguarda Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Flumignan RL, Civile VT, Tinôco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah ÁN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3:CD013739. doi: 10.1002/14651858.CD013739.pub2. Review.

Flumignan RL, Tinôco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah ÁN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10:CD013739. doi: 10.1002/14651858.CD013739. Update in: Cochrane Database Syst Rev. 2022 Mar 4;3: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.

• Responsible Party: Niguarda Hospital
• ClinicalTrials.gov Identifier: NCT04366960
• Other Study ID Numbers: 2020-001708-41
• First Posted: April 29, 2020
• Last Update Posted: June 8, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Niguarda Hospital:

COVID19

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Enoxaparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action