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anticoagulant, curative dose (n=311) vs. anticoagulant, prophylactic dose (n=304)
randomized controlled trial
therapeutic anticoagulation
in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3–0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30.
prophylactic anticoagulation
standard in-hospital enoxaparin or unfractionated heparin
COVID 19 hospitalized
open-label
31 hospitals in Brazil
anticoagulant, curative dose (n=1190) vs. anticoagulant, prophylactic dose (n=1054)
randomized controlled trial
therapeutic-dose anticoagulation with heparin
usual care pharmacological thromboprophylaxis
COVID-19 mild to moderate
open-label
prematurely discontinued after a planned adaptive analysis of data from 1398 patients showed that the prespecified stopping criteria for superiority of therapeutic-dose anticoagulation had been reached in both the high and low d-dimer cohorts
heparin at therapeutic dose (n=228) vs. standard of care (n=237)
randomized controlled trial
Therapeutic heparin (high dose nomogram)
Unfractionated heparin OR low molecular weight heparin (tinzaparin 175 U/kg once per day, enoxaparin 1.5 mg/kg once per day or 1 mg/kg twice per day or dalteparin 200 U/kg administered until discharged from hospital, 28 days or death
Prophylactic heparin
Prophylactic subcutaneous heparin (low molecular weight heparin or unfractionated heparin) adjusted for body mass index and creatinine clearance.
Prophylactic doses of heparin were thus restricted to evidence based protocols for the prevention of venous thromboembolism for medical patients admitted to hospital. Study treatment was started within 24 hours after randomisation and continued until the first of hospital discharge, day 28, study withdrawal, or death. If a participant was admitted to ICU, continuation of the allocated treatment was recommended.
COVID-19 mild to moderate
Moderate illness was defined as admission to hospital ward level of care (ie, not to ICU), not already mechanically ventilated, and not imminently requiring mechanical ventilation or critical care. D-dimer levels were required to be above the upper limit of normal of the local hospital in the presence of an oxygen saturation ≤93% on room air, or ≥2 times the upper limit of normal irrespective of oxygen saturation. Participants were excluded if they had substantial bleeding risks, an absolute indication for or any contraindication to heparin anticoagulation based on care team judgment, were pregnant, or ift hey had already experienced, or would imminently experience any component of the primary outcome (all cause death, non-invasive or invasive mechanical ventilation, or ICU admission).
Open-label, randomized.
Multicenter: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US.
462 participants
anticoagulant, curative dose (n=191) vs. anticoagulant, prophylactic dose (n=191)
randomized controlled trial
full-dose anticoagulation
standard-dose prophylactic anticoagulation
COVID-19 severe or critically
open label
34 centers, United States
2x2 factorial deisgn with clopidogrel or no antiplatelet therapy; recruitment was stopped early in 03/2022 (∼50% planned recruitment) due to waning ICU-level COVID-19 rates
anticoagulant, curative dose (n=591) vs. anticoagulant, prophylactic dose (n=616)
randomized controlled trial
therapeutic anticoagulation with heparin
Therapeutic anticoagulation was administered according to local site protocols for the treatment of acute venous thromboembolism for up to 14 days or recovery
pharmacological thromboprophylaxis as per local usual care
COVID-19 severe or critically
open-blind
NCT02735707, NCT04505774, NCT04359277, NCT04372589
anticoagulation, intermediate prophylactic dose (n=276) vs. anticoagulant, prophylactic dose (n=286)
randomized controlled trial
intermediate-dose prophylactic anticoagulation
enoxaparin, 1mg/kg daily
standard-dose prophylactic anticoagulation
enoxaparin, 40mg daily
COVID-19 severe or critically
open-label
10 academic centers in Iran
2 × 2 factorial design comparing intermediate-dose vs standard-dose prophylactic anticoagulation and statin therapy vs matching placebo
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