Thromboprophylaxis for Patients in ICU With COVID-19

Study Overview
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Brief Summary
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The respiratory distress that goes with COVID-19 infection has been related to a procoagulant state, with thrombosis at both venous and arterial levels, that determines hypoxia and tissue dysfunction at several organs. The main sign of this thrombotic activity seems to be the D-Dimers, that have been proposed to identify patients with poor prognosis at an early stage. Knowledge on how to prevent or even treat this procoagulant state is scarce. COVID-19 patients may be out of general thromboprophylaxis recommendations, and recent studies suggest a better prognosis in severe COVID-19 patients receiving anticoagulant therapy with low molecular weight heparin (LMWH). However, the LMWH efficacy and safety, mainly in patients admitted to an Intensive Care Unit, remains to be validated.

Detailed Description
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Many reports have postulated a procoagulant state along with the respiratory distress caused by coronavirus SARS-CoV2. A complex physiopathology has been proposed trying to explain this profile, mainly based on the thromboinflammatory concept, with thrombosis at both venous and arterial levels. Microvascular thrombi impair the blood flow all over the body, with a vascular shunt due to capillary obstruction, that determines hypoxia and tissue dysfunction at several organs, being the lung the more affected one. Although D-Dimers (DD) are not specific indicators of clot formation, its elevation, in combination with other parameters (hyperfibrinogenemia, mild thrombocytopenia) may suggest a systemic coagulation activation with an increase of thrombin generation and fibrinolysis. In fact, in a retrospective Chinese analysis, a DD higher than 1000 ng/ml was proposed to identify patients with poor prognosis at an early stage. Nevertheless, knowledge on how to prevent or even treat this procoagulant state is scarce. Thromboprophylaxis with low molecular-weight heparin (LMWH) is recommended in most medical patients admitted to the hospital and in nearly all patients in an Intensive Care Unit (ICU). But COVID-19 patients may be out of these recommendations, and some treatment schemes has been proposed, although how to decide the suitable LMWH for each clinical situation is controversial. Recent retrospective studies suggest a better prognosis in severe COVID-19 patients receiving anticoagulant therapy with LMWH. However, the LMWH efficacy and safety, mainly in COVID-19 patients admitted to the ICU, remains to be validated.

Official Title
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Effectiveness of Thromboprophylaxis With Low Molecular Weight Heparin in Critically Ill Patients With COVID-19. A Prospective, Cohort, Multicenter Study.

Conditions
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Covid19, Anticoagulant Therapy, Thrombosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed SARS-CoV2 infection from a respiratory tract sample using a polymerase chain reaction assay. Admitted to ICU Exclusion Criteria: Non-confirmed SARS-CoV2 infection No data at first day ICU admission Patient with do-not resuscitate orders Patient who did not meet the outcomes of death or ICU discharge by the time of study completion date

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anticoagulation<br>Patients receiving an anticoagulant dose (equal or higher than 150 IU/kg/24 h) of LMWH within the first 48 hours after the ICU admission | |
| Thromboprophylaxis<br>Patients receiving a prophylactic dose (lower than 150 IU/kg/24 h) of LMWH within the first 48 hours after the ICU admission | |
| No heparin<br>Patients receiving no anticoagulant drug within the first 48 hours after the ICU admission | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU mortality | Rate of mortality | From admission to ICU discharge, an average of 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU incidence of thrombotic events | A composite endpoint to evaluate efficacy made up of: myocardial infarction, stroke, incidental pulmonary thromboembolism, pulmonary thromboembolism with worsening of hypoxemia, Pulmonary thromboembolism with hemodynamic repercussion, other venous thromboses without pulmonary thromboembolism | From admission to ICU discharge, an average of 1 month | 
| ICU incidence of bleeding events | Composite endpoint to evaluate safety made up of: bleeding needing transfusion, bleeding wit hemodynamic repercussion, other bleeding (minor bleeding) | From admission to ICU discharge, an average of 1 month | 
| Length of ICU stay | Days admitted in ICU | From admission to ICU discharge, an average of 1 month | 
| Length of invasive mechanical ventilation | Days treated with invasive mechanical ventilation (controlled or assisted) | From admission to ICU discharge, an average of 1 month | 
| Effect of LMWH in other parameters | Description of the relationship if any between the use of LMWH and thrombotic or inflammatory parameters (D-Dimer levels, ferritin) or lung dead space | From admission to ICU discharge, an average of 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Low Molecular weight heparin, Thromboprophylaxis, Anticoagulant treatment, Thrombosis