The primary outcome measure was the time to recovery, with the day of recovery defined as the first day, during the 28 days after enrollment, on which a patient attained category 1, 2, or 3 on the eight-category ordinal scale. The competing event of death was handled in a manner similar to the Fine–Gray competing-risk approach.13 (link) The categories are the same as those used in ACTT-11 (link) and are listed in Table S1 in the Supplementary Appendix . The primary analysis was a stratified log-rank test of the time to recovery with remdesivir plus baricitinib as compared with remdesivir plus placebo, stratified according to baseline disease severity (i.e., score on the ordinal scale of 4 or 5 vs. 6 or 7 at enrollment).
The key secondary outcome measure was clinical status at day 15, based on the eight-category ordinal scale. Other secondary outcome measures included the time to improvement by one or two categories from the ordinal score at baseline; clinical status, as assessed on the ordinal scale at days 3, 5, 8, 11, 15, 22, and 29; mean change in the ordinal score from day 1 to days 3, 5, 8, 11, 15, 22, and 29; time to discharge or to a National Early Warning Score of 2 or less (on a scale from 0 to 20, with higher scores indicating greater clinical risk) that was maintained for 24 hours, whichever occurred first; change in the National Early Warning Score from day 1 to days 3, 5, 8, 11, 15, 22, and 29; number of days of receipt of supplemental oxygen, noninvasive ventilation or high-flow oxygen, and invasive ventilation or extracorporeal membrane oxygenation (ECMO) up to day 29 (if these were being used at baseline); the incidence and duration of new use of oxygen, new use of noninvasive ventilation or high-flow oxygen, and new use of invasive ventilation or ECMO; duration of hospitalization up to day 29 (patients who remained hospitalized at day 29 had a value of 28 days); and mortality at 14 and 28 days after enrollment. Secondary safety outcomes included grade 3 and 4 adverse events and serious adverse events that occurred through day 29, discontinuation or temporary suspension of trial-product administration for any reason, and changes in assessed laboratory values over time. There was a single primary hypothesis test. For secondary outcomes, no adjustments for multiplicity were made.
Prespecified subgroups were defined according to sex, disease severity (as defined for stratification and by an ordinal score of 4, 5, 6, and 7 at enrollment), age (18 to 39 years, 40 to 64 years, or ≥65 years), race, ethnic group, duration of symptoms before randomization (measured as ≤10 days or >10 days, in quartiles, and as the median), site location, and presence of coexisting conditions.
The key secondary outcome measure was clinical status at day 15, based on the eight-category ordinal scale. Other secondary outcome measures included the time to improvement by one or two categories from the ordinal score at baseline; clinical status, as assessed on the ordinal scale at days 3, 5, 8, 11, 15, 22, and 29; mean change in the ordinal score from day 1 to days 3, 5, 8, 11, 15, 22, and 29; time to discharge or to a National Early Warning Score of 2 or less (on a scale from 0 to 20, with higher scores indicating greater clinical risk) that was maintained for 24 hours, whichever occurred first; change in the National Early Warning Score from day 1 to days 3, 5, 8, 11, 15, 22, and 29; number of days of receipt of supplemental oxygen, noninvasive ventilation or high-flow oxygen, and invasive ventilation or extracorporeal membrane oxygenation (ECMO) up to day 29 (if these were being used at baseline); the incidence and duration of new use of oxygen, new use of noninvasive ventilation or high-flow oxygen, and new use of invasive ventilation or ECMO; duration of hospitalization up to day 29 (patients who remained hospitalized at day 29 had a value of 28 days); and mortality at 14 and 28 days after enrollment. Secondary safety outcomes included grade 3 and 4 adverse events and serious adverse events that occurred through day 29, discontinuation or temporary suspension of trial-product administration for any reason, and changes in assessed laboratory values over time. There was a single primary hypothesis test. For secondary outcomes, no adjustments for multiplicity were made.
Prespecified subgroups were defined according to sex, disease severity (as defined for stratification and by an ordinal score of 4, 5, 6, and 7 at enrollment), age (18 to 39 years, 40 to 64 years, or ≥65 years), race, ethnic group, duration of symptoms before randomization (measured as ≤10 days or >10 days, in quartiles, and as the median), site location, and presence of coexisting conditions.
