Connors 2021 (ACTIV‐4B).

Study characteristics
Methods	Trial design: multicentre, adaptive, randomised, double‐blind, placebo‐controlled platform trial Type of publication: journal publication Setting: non‐hospitalised participants Recruitment dates: September 2020 to June 2021 Country: United States Language: English Number of centres: 52 Inclusion criteria COVID‐19 + in past 14 days Platelets > 100,000 eGFR > 30 mL/min Exclusion criteria Hospitalised for COVID‐19 Active cancer Recent major bleeding Contradiction/other indication for anticoagulation Pregnancy (or lactating) Trial registration number: NCT04498273 Date of trial registration: 4 August 2020
Participants	Age: median (IQR); 54 years (IQR, 46 to 59) Gender: 59.1% women Ethnicity: 12.7% Black, 28.1% Hispanic Number of participants (recruited/allocated/evaluated): 657 randomised, of whom 164 were randomised to receive acetylsalicylic acid, 164 to receive placebo, 165 to receive apixaban in prophylactic dose and 164 to receive apixaban in therapeutic dose Severity of disease: symptomatic SARS‐CoV‐2 infection (COVID‐19) verified by positive polymerase chain reaction or antigen test Additional diagnoses (intervention vs control): hypertension 34% vs 33%, diabetes (self‐reported) 18% vs 14%, history of smoking 24% vs 19% Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): NR
Interventions	Study arms Placebo Drug: prophylactic dose apixaban 2.5 mg Drug: therapeutic dose apixaban 5.0 mg Drug: acetylsalicylic acid 81 mg Details of intervention Antiplatelet agent: low‐dose acetylsalicylic acid 81 mg orally once a day for 45 days Control group: matching placebo once a day
Outcomes	Primary outcome: composite of symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischaemic stroke, hospitalisation for cardiovascular or pulmonary events and all‐cause mortality for up to 45 days after treatment initiation Secondary outcomes: individual components of the primary study end point as well as mortality without antecedent hospitalisation
Notes	Sponsor: This study was, in part, funded by National Institutes of Health (NIH) Agreement 1OT2HL156812‐01. Specifically, the ACTIV‐4B trial was supported by Other Transition Authorities from the National Heart, Lung, and Blood Institute (NHLBI). Grantee institutions included the University of Pittsburgh; the University of Illinois Chicago; and the Brigham and Women's Hospital. The trial drugs and matching placebo were donated by the Bristol Myers Squibb–Pfizer Alliance. COI Dr Connors reported receiving personal fees from Bristol Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi and that his institution has received research funding from CSL Behring. Dr Brooks reported receiving personal fees for data and safety monitoring board membership from Cerus Corporation. Dr Krishnan reported receiving grants from Sergey Brin Family Foundation Research in COVID. Dr Bledsoe reported receiving grants payable his institution from the National Institutes of Health (NIH) for clinical trial work and receiving consulting fees from JAJ LLC. Dr Kirwan reported receiving grants from SOCAR Research SA. Dr Everett reported receiving consulting fees from Johnson & Johnson, Gilead, and Merck. Dr Hou reported receiving grants from Brigham and Women’s Hospital, NIH, Novartis, and CalciMedica. Dr Haight reported receiving grants and nonfinancial support from OneFlorida. Dr Wilson reported receiving personal fees from Pfizer, Bristol Myers Squibb, Alexion, Janssen, and Paratek and receiving grants from Gilead. Dr Ridker reported receiving grants from Bristol Myers Squibb and Pfizer and serving as a consultant for work unrelated to this study for Corvidia, Novartis, Flame, Agepha, Inflazome, AstraZeneca, Jannsen, Civi Biopharm, SOCAR, Novo Nordisk, Uptton, Omeicos, and Boehringer Ingelheim. No other authors reported disclosures.