Publication ACTIV-4a - Berger JS, JAMA (2022) (published paper)
Dates: 2021-02-26 to 2021-06-19
Funding: Public/non profit (National Institutes of Health; National Heart, Lung, and Blood Institute )
Conflict of interest: Yes
Multicenter / Brazil, Italy, Spain, USA |
Follow-up duration (days): 90
Therap AC + P2Y12 inh
If Ticagrelor: 60 mg twice daily for 14 days or until hospital discharge, whichever was sooner. If Clopidogrel: Initial dose: 300 mg load dose -Maintenance dose: 75 mg/day, for 14 days or until hospital discharge, whichever was sooner.
Therap AC + P2Y12 inh=293
|Characteristics of participants|
Mean age : NR
Severity : Mild: n=58 / Moderate: n=343 / Severe: n=99 Critical: n=0
Number of vaccinated participants: NR
|In the register|
1) 21 Day Organ Support (respiratory or vasopressor) Free Days [Time Frame: 21 days from study enrollment]: which is defined as the number of days that a patient is alive and free of organ support through the first 21 days after trial entry. Organ Support is defined as receipt of non-invasive mechanical ventilation, high flow nasal canula oxygen, mechanical ventilation, or vasopressor therapy, with death at any time during the index hospitalization assigned -1 days. 2) Primary Safety Endpoint of Major Bleeding [Time Frame: 28 days from study enrollment]: Major bleeding (as defined by the ISTH).
|In the report|
1) 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 hospitalization (range, −1 to 21 days; higher scores indicate less organ support and better outcomes); 2) Major bleeding by 28 days (as defined by the International Society on Thrombosis and Hemostasis).
Yes. In English
Data-sharing willing stated in the publication:
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
|General comment||In addition to the published article, the registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. This article reports on a non–critically ill cohort, to which enrollment was discontinued when the pre-specified criterion for futility was met. The study continued in a critically ill cohort. There is no change from the trial registration in the intervention and control treatments. Ticagrelor was the preferred P2Y12 inhibitor used: 63% in intervention group received ticagrelor; 37% had clopidogrel. The primary outcome in the article reflects that in the registry. The trial (n = 562) was stopped due to futility at repeated monthly interim analyses; the trial had an adaptive sample size of 200-2000 participants.|