Trial NCT04501978
Publication ACTIV-3/TICO LY-CoV555 Study Group, N Engl J Med, 2020
Primary outcome on the report: Time to a sustained recovery, which was defined as hospital discharge to home and remaining at home for at least 14 days. Two ordinal outcomes that are measuredat day 5 bothclassified according to seven-level ordinal scales,are termed pulmonary and pulmonary-plus outcomes.The primary safety outcome was a composite of death, serious adverse events, or grade 3 or 4 adverse events through day 5.
Bias Author's judgement Support for judgement
Randomization
Low 		Quote: "Hospitalized patients with Covid-19 were randomly assigned in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including remdesivir and, when indicated, supplemental oxygen and glucocorticoids. Randomization was stratified according to the trial pharmacy, since each pharmacy could serve more than one trial site. LY-CoV555 or placebo was administered as a single intravenous infusion over a 1-hour period. The infusion was prepared by trial pharmacists. All other personnel, including investigators and research staff, clinical staff, and patients, were unaware of the trial-group assignments."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Low 		Quote (report): “The infusion was prepared by trial pharmacists. All other personnel, including investigators and research staff, clinical staff, and patients, were unaware of the trial-group assignments.”
Quote (protocol): “blinding of the participant and clinical staff will be achieved by placing a colored sleeve over the infusion bags used for investigational agents and placebos”
Comment: Blinded study (patients and physicians).
Data were analyzed using modified intention-to-treat analysis (a small proportion not included was randomized on day of termination and never received treatment or follow up) which is appropriate to assess the effect of assignment to intervention.
Missing outcome data
Low 		Comment: 326 patients randomized; 314 patients analyzed.
Data available for >95% of population.
Risk assessed to be low for the outcomes: Mortality. Time to death. Clinical improvement. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events.
Measurement of the outcome
Low 		Comment: Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality. Time to death. Clinical improvement. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan and trial registry were available.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality. Time to death. Clinical improvement. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events.
Overall risk of bias
Low