Patient Representatives

Enrollment for ACTT-1 began on February 21, 2020, and ended on April 19, 2020. There were 60 trial sites and 13 subsites in the United States (45 sites), Denmark (8), the United Kingdom (5), Greece (4), Germany (3), Korea (2), Mexico (2), Spain (2), Japan (1), and Singapore (1). Eligible patients were randomly assigned in a 1:1 ratio to receive either remdesivir or placebo. Randomization was stratified by study site and disease severity at enrollment. Patients were considered to have severe disease if they required mechanical ventilation, if they required supplemental oxygen, if the oxygen saturation as measured by pulse oximetry (Spo₂) was 94% or lower while they were breathing ambient air, or if they had tachypnea (respiratory rate ≥24 breaths per minute). Remdesivir was administered intravenously as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily on days 2 through 10 or until hospital discharge or death. A matching placebo was administered according to the same schedule and in the same volume as the active drug. A normal saline placebo was used at the European sites and at some non-European sites owing to a shortage of matching placebo; for these sites, the remdesivir and placebo infusions were masked with an opaque bag and tubing covers to maintain blinding. All patients received supportive care according to the standard of care for the trial site hospital. If a hospital had a written policy or guideline for use of other treatments for Covid-19, patients could receive those treatments. In the absence of a written policy or guideline, other experimental treatment or off-label use of marketed medications intended as specific treatment for Covid-19 were prohibited from day 1 through day 29 (though such medications could have been used before enrollment in this trial).
The trial protocol was approved by the institutional review board at each site (or by a centralized institutional review board as applicable) and was overseen by an independent data and safety monitoring board. Written informed consent (or consent by other institutional review board-approved process) was obtained from each patient or from the patient’s legally authorized representative if the patient was unable to provide consent. Full details of the trial design, conduct, oversight, and analyses can be found in the protocol and statistical analysis plan (available with the full text of this article at NEJM.org).