Covid-19 Living Data

Trial NCT04498273
Publication ACTIV-4B - Connors JM, JAMA (2021) (published paper)
Dates: 2020-09-01 to 2021-06-17
Funding: Public/non profit (National Institutes of Health; Other Transition Authorities from the National Heart, Lung, and Blood Institute (NHLBI); University of Pittsburgh; University of Illinois Chicago; Brigham and Women’s Hospital. Bristol Myers Squibb–Pfizer Alliance (drug donation))
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA Follow-up duration (days): 75
Inclusion criteria	Ambulatory patients between the ages of 40 and 80 years with newly diagnosed symptomatic SARS-CoV-2 infection with positive polymerase chain reaction or antigen test results Creatinine clearance was required to be greater than 30mL/min/1.73m2 Platelet count greater than 100 000/mm3 Have the ability to be contacted by telephone and, optionally, other electronic methods of communication
Exclusion criteria	Patient who had been previously hospitalized for COVID-19 Had acute leukemia Recent major bleeding Contraindication to or other indication for anticoagulation Need for single or dual antiplatelet therapy Pregnant or lactating
Interventions
	Treatment Aspirin 81 mg orally once daily for 45 days Apixaban prophylactic 2.5 mg orally twice daily for 45 days Apixaban therapeutic 5 mg orally twice daily for 45 days
	Control Placebo
Participants
	Randomized participants : Aspirin=164 Apixaban prophylactic=165 Apixaban therapeutic=164 Placebo=164
	Characteristics of participants N= 657 Mean age : NR 269 males Severity : Mild: n= 657/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Hospitalization for cardiovascular/pulmonary events [ Time Frame: 45 days ] The primary outcome will be a composite endpoint of need for hospitalization for cardiovascular/pulmonary events, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality for up to 45 days after initiation of assigned treatment.
	In the report Composite of symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, hospitalization for cardiovascular or pulmonary events, and all-cause mortality for up to 45 days after treatment initiation
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the study registry, protocol, statistical analysis plan and supplementary appendix were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments, as well as primary outcome. The registry primary outcome does not reflect the reported secondary outcomes. Adverse events are not reported. Furthermore, the study was terminated early on and not all randomized participants received their assigned treatment. "On June 18, 2021, the NHLBI accepted a recommendation from the independent data and safety monitoring board to terminate the trial early because of lower than anticipated event rates (Supplement 3); for this reason, despite the adaptive clinical trial design, no additional agents underwent evaluation." The extraction and risk of bias assessments were updated on April 25th, 2022 after contact with the authors.