NCT04401293.

Study name	Systemic anticoagulation with full dose low molecular weight heparin (LMWH) vs. prophylactic or intermediate dose LMWH in high risk COVID‐19 patients (HEP‐COVID Trial)
Starting date	26 April 2020
Contact information	Damian N Inlall Northwell Health, USA (516) 600‐1482 | dinlall@northwell.edu
Methods	Multicenter, prospective, triple blinded, 2‐armed, parallel‐assignment RCT
Participants	308 participants, ≥ 18 years, female and male Inclusion criteria Participant (or legally authorised representative) provides written informed consent prior to initiation of any study procedures Understands and agrees to comply with planned study procedures Male or non‐pregnant female adult ≥ 18 years of age at time of enrolment Participant consents to randomisation within 72 h of hospital admission or transfer from another facility within 72 h of index presentation Participants with a positive COVID‐19 diagnosis by nasal swab or serologic testing Hospitalised with a requirement for supplemental oxygen Have: either a D‐dimer > 4.0 x ULN, OR SIC score of ≥ 4 Exclusion criteria Indications for therapeutic anticoagulation Absolute contraindication to anticoagulation including: active bleeding recent (within 1 month) history of bleed dual (but not single) antiplatelet therapy active gastrointestinal and intracranial cancer a history of bronchiectasis or pulmonary cavitation hepatic failure with a baseline INR > 1.5 creatine clearance < 15 mL/min a platelet count < 25,000 a history of HIT within the past 100 days or in the presence of circulating antibodies contraindications to enoxaparin including a hypersensitivity to enoxaparin sodium, hypersensitivity to heparin or pork products, hypersensitivity to benzyl alcohol pregnant female inability to give or designate to give informed consent participation in another blinded trial of investigational drug therapy for COVID‐19
Interventions	Experimental: full‐dose LMWH anticoagulation therapy Participants in this study arm will be treated with therapeutic doses of SC LMWH (enoxaparin). Enoxaparin 1 mg/kg SC twice a day for creatinine clearance ≥ 30 mL/min (or enoxaparin 0.5 mg/kg SC twice a day for creatinine clearance ≥ 15 mL/min and < 30 mL/min) during the course of their hospitalisation. Comparator: prophylactic/intermediate‐dose LMWH or UFH therapy Participants in this study arm will be treated with local institutional standard of care for prophylactic‐dose or intermediate‐dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in twice daily or three times daily doses (i.e. UFH 5000 IU SC twice a day/three times a day or 7500 IU twice a day/three times a day), enoxaparin 30 mg and 40 mg SC daily or twice daily (the use of weight‐based enoxaparin i.e. 0.5 mg/kg SC twice a day for this arm is acceptable but strongly discouraged), dalteparin 2500 IU or 5000 IU a day
Outcomes	Primary Composite outcome of arterial thromboembolic events, venous thromboembolic events and all‐cause mortality at day 30 ± 2 days (time frame: day 30 ± 2 days). Risk of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), VTE (including symptomatic DVT of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non‐fatal PE), and all‐cause mortality at day 30 ± 2 days. Secondary Major bleeding (time frame: day 30 ± 2 days). Risk of major bleeding defined using the ISTH criteria Composite outcome of arterial thromboembolic events, venous thromboembolic events and all‐cause mortality at hospital day 10 + 4 (time frame: day 10 + 4). The composite of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), VTE (including symptomatic DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non‐fatal PE), and all‐cause mortality at hospital day 10 + 4 SIC score (time frame: day 30 ± 2 days). SIC score based on ISTH guidelines. Platelets, K/uL (thousands per microlitre) (0‐2) INR (0‐2) D‐Dimer Levels, ng/mL (0‐3) Fibrinogen, mg/dL (0‐1) Calculated (SIC) scores ≥ 4 predicted higher mortality rates within 30 days and greater risk of PE Progression to ARDS (time frame: day 30 ± 2 days) based on monitoring of participant conditions Need for intubation (time frame: day 30 ± 2 days.) based on monitoring of participant conditions Re‐hospitalisation (time frame: day 30 ± 2 days) based on monitoring of participant conditions
Notes	NCT04401293 | No data provided