Aspirin vs Standard care/Placebo (RCT)

Mild outpatients

On March 17, 2022 study Ghati, 2021 was excluded from the analysis since the paper is not anymore accessible on SSRN nor on published elsewhere. We have contacted authors for further details. FOREST PLOTS -2022-04-29

Studies description

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
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
avalaible

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.