Sholzberg 2021a.

Study name	Coagulopathy of COVID‐19: a pragmatic randomized controlled trial of therapeutic anticoagulation versus standard care as a rapid response to the COVID‐19 pandemic (RAPID COVID COAG)
Starting date	11 May 2020
Contact information	Michelle Sholzberg St. Michael's Hospital, Toronto, Ontario, Canada 416‐864‐5389 | Michelle.Sholzberg@unityhealth.to
Methods	Multicentre, quadruple masking (participant, care provider, investigator, outcomes assessor), investigator‐sponsored, 2‐armed, parallel‐assignment RCT
Participants	462 participants, ≥ 18 years, female and male Inclusion criteria Laboratory‐confirmed diagnosis of SARS‐CoV‐2 via RT‐PCR as per the WHO protocol or by nucleic acid‐based isothermal amplification Admitted to hospital 1 D‐dimer value ≥ 2 times ULN (within 72 h of hospital admission) ≥ 18 years Informed consent from the participant (or legally authorised substitute decision maker) Exclusion criteria Pregnancy BMI < 18.5 kg/m² or ≥ 40 kg/m² Haemoglobin < 80 g/L in the last 72 h Platelet count < 50 x 109/L in the last 72 h Known fibrinogen < 1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation) Known INR > 1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation) Participant already on intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high‐risk participants into consideration) Participant already on therapeutic anticoagulation at the time of screening (low‐ or high‐dose nomogram UFH, LMWH, warfarin, DOAC (any dose of dabigatran, apixaban, rivaroxaban, edoxaban) Participant on dual antiplatelet therapy, when one of the agents cannot be stopped safely Known bleeding within the last 30 days requiring emergency room presentation or hospitalisation Known history of a bleeding disorder of an inherited or active acquired bleeding disorder Known history of HIT Known allergy to UFH or LMWH Admitted to the ICU at the time of screening Treated with non‐invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening (of note: high‐flow oxygen delivery via nasal cannula is acceptable and is not an exclusion criterion)
Interventions	Experimental: therapeutic anticoagulation Therapeutic anticoagulation with LMWH or UFH (high‐dose nomogram). The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply Therapeutic anticoagulation will be administered until discharged from hospital, 28 days or death. If the participant is admitted to the ICU or requiring ventilatory support, we recommend continuation of the allocated treatment as long as the treating physician is in agreement Comparison: standard care In Canada and the USA, administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalised medical patients, in the absence of contraindication, is considered standard care
Outcomes	Primary Composite outcome of ICU admission (yes/no), non‐invasive positive pressure ventilation (yes/no), invasive mechanical ventilation (yes/no), or all‐cause death (yes/no) up to 28 days (time frame: up to 28 days) Secondary All‐cause death (time frame: up to 28 days) Composite outcome of ICU admission or all‐cause death (time frame: up to 28 days) Major bleeding (time frame: up to 28 days). Major bleeding as defined by the ISTH Scientific and Standardization Committee recommendation Number of participants who received red blood cell transfusion (time frame: up to 28 days). Red blood cell transfusion (≥ 1 unit) Number of participants with transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate (time frame: up to 28 days) Number of hospital‐free days alive up to day 28 (time frame: up to 28 days) Number of ICU‐free days alive up to day 28 (time frame: up to 28 days) Number of ventilator‐free days alive up to day 28 (time frame: up to 28 days) Number of participants with VTE (time frame: up to 28 days) Number of participants with arterial thromboembolism (time frame: up to 28 days) Number of participants with HIT (time frame: up to 28 days) Changes in D‐dimer up to day 3 (time frame: up to day 3)
Notes	NCT04362085 | No data provided