Bivalirudin Versus Enoxaparin in Critically Ill COVID-19 Patients

Study Overview
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Brief Summary
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Coronavirus Disease (COVID-19) is characterized by a hypercoagulable state, sometimes difficult to be managed with heparin. Bivalirudin, a member of the direct thrombin inhibitor drug class, offers potential advantages compared to heparin, including to its ability to exert its effect by directly attaching to and inhibiting freely circulating and fibrin-bound thrombin. Investigators have therefore designed this pilot open-label randomized controlled trial to assess if a off-label infusion of bivalirudin may reduce thrombosis, mortality, Intensive Care Unit (ICU) length of stay and increase ventilator free days of patients admitted in ICU for acute respiratory failure due to COVID-19, as compared to first-line treatment with heparin.

Official Title
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Bivalirudin Versus Enoxaparin for Anticoagulation in Critically Ill COVID-19 Patients: a Pilot Randomized Controlled Trial

Conditions
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Acute Respiratory Failure, SARS CoV 2 Infection, Anticoagulants

Intervention / Treatment
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* Drug: Enoxaparin Sodium
* Drug: Bivalirudin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ratio between arterial partial pressure to inspired fraction of oxygen (PaO2/FiO2) < 200 mmHg age equal or greater of 18 years/old detection of coronavirus 2019 at the nasal swab; need for endotracheal intubation and invasive mechanical ventilation Exclusion Criteria: known allergies to one of the two investigated drugs presence of hematological diseases pregnancy recent (10 days) surgery presence of active bleeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enoxaparin sodium<br>Enoxaparin sodium twice daily, according to the renal function and clinical indication | Drug: Enoxaparin Sodium<br>* Enoxaparin will be subcutaneously administered at a dosage from 4000 to 8000 twice daily according<br>|
| Experimental: Bivalirudin<br>Bivalirudin will be administered by continuous infusion, until day 7. Bivalirudin will be administered at dosage of 0,25 mg/kg in first 30 minutes, followed by continuous infusion of 0,2 mg/kg/h until 7 days. The infusion rate will be adjusted targeting a prothrombin time ratio of about 1.5. | Drug: Bivalirudin<br>* Bivalirudin will be intravenously administered to obtain an activated prothrombin time (aPTT) of 1.5 fold of the normal values.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent under invasive mechanical ventilation | number of days that patient would require invasive mechanical ventilation | from randomization till 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of vein thrombosis and embolism | Number of patients with diagnosis of deep vein thrombosis and/or pulmonary embolism | from randomization till 28 days after randomization or ICU discharge | 
| Gas Exchange | Daily evaluation of oxygenation through arterial blood gases | Every day till 28 days after randomization or ICU discharge | 
| Intensive Care Unit length of stay | Number of days spent in Intensive Care Unit | Up to 1 year | 
| Intensive Care Unit mortality | Number of patients died during the Intensive Care Unit stay | Up to 1 year |