Covid-19 Living Data

Trial NCT04790786
Publication OPTIMISE-C19 - Huang D, JAMA Netw Open (2022) (published paper)

Funding: Mixed (The Federal COVID Response Team (formerly called Operation Warp Speed) supplies mABs to UPMC, participates in design discussions, and is provided regular updates. UPMC supports this trial with resources and internal funds, and leadership was involved in all aspects of the trial including design, analysis, data interpretation, and manuscript preparation. The US government provided casirivimab-imdevimab, and GlaxoSmithKline and Vir Biotechnology provided sotrovimab. Preliminary results were shared with GlaxoSmithKline and Vir Biotechnology before preprint submission, but the organization had no role in manuscript preparation or interpretation of results.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	Outpatients mild to moderate infection with COVID-19 positive aged 12-120 years eligible for mAB under FDA EUA. As per the current EUA criteria: Adult (> 18 years old) Children > 12 years old weighing at least 40 kg With a positive SARS-CoV-2 antigen or PCR test and within 10 days of symptom onset High risk of disease progression. High risk is defined as patients who meet at least one of the following criteria: A Body Mass Index (BMI) ≥ 35 Have chronic kidney disease Have diabetes Have immunosuppressive disease Are currently receiving immunosuppressive treatment Are ≥ 65 years old Are ≥ 55 years of age AND have cardiovascular disease, OR hypertension, OR chronic obstructive pulmonary disease/other chronic respiratory disease. Are 12-17 years of age AND have: BMI≥85th percentile for their age and gender based on CDC growth charts, OR sickle cell disease, OR congenital or acquired heart disease, OR neurodevelopmental disorders (eg, cerebral palsy), OR amedical-related technological dependence, for example, tracheostomy or gastrostomy), OR asthma, reactive airway or other respiratory disease that requires daily medication for control.
Exclusion criteria	Are hospitalized for the treatment of COVID-19 Require oxygen therapy for the treatment of COVID-19 Require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity Have a known hypersensitivity to any antibody ingredient death is deemed to be imminent or inevitable Previous participation in this REMAP within the last 90 days.
Interventions
	Treatment Sotrovimab 500 mg Intravenously single dose
	Control REGN-COV2 2400 mg (1200 mg of each drug) intravenously single dose
Participants
	Randomized NR Analyzed 3558 participants Sotrovimab=1104 REGN-COV2=2454
	Characteristics of participants N= 3558 Mean age : NR 1639 males Severity : Mild: n= 3558/ Asymptomatic: n=0 Number of vaccinated participants: 339
Primary outcome
	In the register Alive and Free from Hospitalization [Time Frame: 28 days after initial participation]: Days alive and free from hospitalization. Patients that are both living and not in the hospital will meet criteria to be counted in this outcome.
	In the report Hospital-free days up to day 28 after mAb treatment. This outcome was an ordinal end point, with death as the worst outcome (labeled as −1) followed by the length of time alive and free of hospitalization, such that the best outcome would be 28 hospital-free days. If a patient had intervening days free of hospitalization and was then rehospitalized, the patient was given credit for the intervening days as free of hospitalization.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
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 trial registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. There is no change from the trial registration in the intervention and control treatments. The primary outcome in the article reflects that in the registry. Some outcomes from the registry are not reported in the paper (e.g., mortality at 90 days, viral negative conversion). Authors noted, "With a pragmatic adaptive design, this trial had no set sample size; the sample size was dependent on case volume, mAb treatment capacity, and meeting predetermined statistical thresholds for equivalence or inferiority." The article reports an early analysis to September 2021 conducted in the context of the Delta crisis. NCT reports much higher recruitment with end of study in June 2022.