heparin at therapeutic dose (n=228) vs. standard of care (n=237)
randomized controlled trial
some concerns about risk of bias
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.