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Low recruitement
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The ongoing COVID-19 pandemic affects millions of humans worldwide and has led to thousands of acute medical hospitalizations. There is evidence that hospitalized cases often suffer from an important infection-related coagulopathy and from elevated risks of thrombosis. Anticoagulants may have positive effects here, to reduce the burden of thrombotic disease and the hyperactivity of coagulation, and may also hold beneficial anti-inflammatory effects against sepsis and the development of ARDS.
The investigators hypothesize that high-dose anticoagulants, compared with low-dose anticoagulants, lower the risk of venous and arterial thrombosis, disseminated intravascular coagulation (DIC) and mortality. This open-label controlled trial will randomize hospitalized adults with severe COVID-19 infection to therapeutic anticoagulation vs. thromboprophylaxis during the hospital stay.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Therapeutic anticoagulation | Experimental | Participants will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or intravenous unfractionated heparin, from admission until the end of hospital stay or clinical recovery. |
|
| Prophylactic anticoagulation | Active Comparator | Participants will be treated with prophylactic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or unfractionated heparin, from admission until the end of hospital stay or clinical recovery. If hospitalized in the intensive care unit, they will receive an augmented thromboprophylaxis regimen as standard of care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enoxaparin | Drug | Two different doses of anticoagulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite outcome of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality | Risk of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality | 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial thrombosis | Risk of ischemic stroke, myocardial infarction and/or limb ischemia | 30 days |
| Venous thromboembolism | Risk of symptomatic venous thromboembolism or asymptomatic proximal leg deep vein thrombosis |
| Measure | Description | Time Frame |
|---|---|---|
| Major bleeding | Risk of ISTH-defined major bleeding | 30 days |
| Clinically relevant non-major bleeding | Risk of ISTH-defined CRNMB | 30 days |
Inclusion Criteria: adult patient with COVID-19 infections, admitted to:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Geneva University Hospitals | Geneva | Switzerland | ||||
| Centre Hospitalier Universitaire Vaudois (CHUV) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35244208 | Derived | 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: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2. | |
| 33502773 | Derived | 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. |
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| ID | Term |
|---|---|
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017984 | Enoxaparin |
| D006493 | Heparin |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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| 30 days |
| Disseminated intravascular coagulation | Risk of DIC | 30 days |
| All-cause mortality | Risk of all-cause mortality | 30 days |
| Sepsis-induced coagulopathy | Risk of SIC | 30 days |
| Acute respiratory distress syndrome | Risk of ARDS | 30 days |
| Durations of hospital stay, ICU stay, ventilation | Number of days with these care processes | 30 days |
| Sequential organ failure assessment score | Highest score per participant | 30 days |
| Clinical deterioration | Risk of clinical deterioration | 30 days |
| Heparin-induced thrombocytopenia | Risk of documented HIT | 30 days |
| PaO2/FiO2 index | Measures of PaO2/FiO2 among participants with mechanical ventilation | 30 days |
| Lausanne |
| Switzerland |
| Ospedale Regionale di Locarno | Locarno | Switzerland |
| Hôpital du Valais | Sion | Switzerland |
| 32407672 | Derived | 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. |