Berger 2022.

Study characteristics
Methods	Trial design: open‐label, Bayesian, adaptive randomised clinical trial Type of publication: journal publication Setting: hospitalised participants Recruitment dates: September 2020 to June 2021 Country: USA, Brazil, Italy, Spain Language: English Number of centres: n.i. Inclusion criteria Laboratory confirmed COVID‐19 + hospitalised without the need for intensive care (non‐critically ill cohort) D‐dimer level 2‐fold or greater than the upper limit of normal (determined at each hospital site) or 60 to 84 years of age If younger than 60 years, enrolment if at least 1 of the following criteria met: oxygen requirement > 2 L per minute or hypertension, diabetes, chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2), cardiovascular disease, or a body mass index of 35 or greater Exclusion criteria If 72 hours or more had elapsed from the hospital admission for COVID‐19 or SARS‐CoV‐2 infection confirmation Hospital discharge expected within 72 hours Contraindication to P2Y12 inhibitors or a clinical requirement for dual antiplatelet therapy Trial registration number: NCT04505774 Date of trial registration: 10 August 2020
Participants	Age: mean age, 52.7 (SD, 13.5) years Gender: 41.5% women Ethnicity: 58.5% White, 28.7% Hispanic, 26.2% Black, 2.9% Asian, 3.3% American Indian or Alaska Native Number of participants (recruited/allocated/evaluated): 562/293 were randomised to receive a therapeutic dose of heparin plus a P2Y12 inhibitor, 269 to receive therapeutic heparin as standard care/ 562 evaluated Severity of disease: symptomatic SARS‐CoV‐2 infection (COVID‐19), laboratory confirmed, hospitalised without need for intensive care unit treatment (non‐critically ill cohort) Additional diagnoses: cardiovascular disease 43.7% intervention vs 55.8% standard care (hypertension, heart failure, coronary artery disease, peripheral artery disease, cerebrovascular disease), other diseases and chronic conditions: diabetes, chronic kidney disease, liver disease, respiratory disease (COPD, asthma) Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): 65.5% vs 62.5% glucocorticoids, 56.0% vs 47.6% remdesivir, 15.0% vs 13.4% acetylsalicylic acid, anticoagulant therapy 10.6% vs 14.5%, 2.7% vs 3.9% IL‐6 inhibitors, 77.8% vs 78.4% low‐flow oxygen, 0.8% vs 0.4% high‐flow nasal cannula
Interventions	Intervention: therapeutic dose anticoagulation + P2Y12 inhibitor (heparin standard care with an added P2Y12), of whom 63.2% received ticagrelor and 36.8% clopidogrel (89.5% with recommended loading dose) for 14 days or until hospital discharge; whichever occurred first Control: therapeutic dose anticoagulation for 14 days or until hospital discharge; whichever occurred first
Outcomes	Composite primary outcome Organ support‐free days evaluated on an ordinal scale that combined in‐hospital death (assigned a value of −1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalisation (range, −1 to 21 days; higher scores indicate less organ support and better outcomes) Components of the primary outcome Alive and free of organ support Alive with organ support Death (in‐hospital) up to day 28 Survival to hospital discharge Death (overall) up to day 21 Secondary outcomes (at day 28) and individual components Major thrombotic event (myocardial infarction, pulmonary embolism, ischaemic stroke, systemic arterial embolism) or in‐hospital death Any thrombotic event (major thrombotic events plus deep venous thrombosis) or in‐hospital death Major bleeding event or in‐hospital death Components of the secondary outcomes In‐hospital death Major thrombotic event Any thrombotic event Major bleeding event
Notes	Funded by the National Institutes of Health Sponsor: National Heart, Lung, and Blood Institute Grants received by study authors: diverse national institutes (i.e. AHA, Agency for Healthcare Resources, rtc.), Astra Zeneca, Janssen, Amgen, and Amarin, Cerus Corp, Abbott Vascular, Siemens, and BioTelemetry, Bayer Pharmaceuticals, Boehringer Ingelheim, Medtronic, Merck, Pfizer, Portola, and Sanofi, Bristol Myers Squibb, Amgen, Novartis, and Novo Nordisk, Cerenovus, Basking Biosciences, Lumosa, Diamedica, Sharp & Dohme, Omron Healthcare Inc, Amgen, Espero BioPharma, Sunovion Pharmaceuticals, Haemonetics, Instrumentation Laboratories, Accriva, Haemonetics, and Haima Therapeutics