Sotrovimab vs Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2022-01-04

Studies description

Trial NCT04501978
Publication ACTIV-3 - Self WH, Lancet Infect Dis (2021) (published paper)
Dates: 2020-12-16 to 2021-03-01
Funding: Mixed (Medications provided by Vir/GlaxoSmithKline; Brii Biosciences; Gilead Sciences; US Operation Warp Speed programme, NIAID; Leidos Biomedical Research for the INSIGHT Network; NHLBI; the Research Triangle Institute for the Prevention; Early Treatment of Acute Lung Injury Network; Cardiothoracic Surgical Trials Network; the Office of Research & Development; US Department of Veterans Affairs; governments of Denmark, United Kingdom; NIH.)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / Denmark, Poland, Switzerland, USA
Follow-up duration (days): 90
Inclusion criteria
  • Adults (aged ≥18 years)
  • Admitted to hospital for acute medical care for COVID-19
  • Laboratory-confirmed SARS-CoV-2 infection (PCR or nucleic acid test)
  • COVID-19 symptoms for up to 12 days
  • Receiving no oxygen therapy or standard oxygen therapy via a nasal cannula or mask
Exclusion criteria
  • Received any SARS-CoV-2 neutralising monoclonal antibodies, hyperimmune immunoglobulin to SARS-CoV-2, or convalescent plasma from a person recovered from COVID-19 any time before admission to hospital
  • receiving high-flow oxygen via nasal cannula, non-invasive ventilation, or invasive mechanical ventilation
  • Met any of the other criteria for acute organ failure or major extrapulmonary manifestations of COVID-19
Interventions
Treatment
Sotrovimab
500 mg intravenously once-off over 60 minutes

BRII-196/BRII-198
1000 BRII-196 mg + 1000 mg BRII-198 intravenously once-off over 60 minutes
Control
Placebo

Participants
Randomized
participants :
Sotrovimab=184
Placebo=183
BRII-196/BRII-198 =179
Characteristics of participants
N= 546
Mean age : NR
308 males
Severity : Mild: n=176 / Moderate: n=360 / Severe: n=0 Critical: n=0
Primary outcome
In the register
Time from randomization to sustained recovery [ Time Frame: Up to Day 90 ] Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
In the report
Time to sustained clinical recovery up to day 90, defined as time between randomisation and return to home (with home defined as the patient's residence before COVID-19 or a location that provided similar or less intensive medical care) for 14 consecutive days.
Documents
avalaible

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes
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
Low
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. The primary outcome in the article reflected that in the registry. The study (n = 546) achieved the target sample size for the early futility assessment (n = 450), but recruitment was terminated as a result of the interim analysis so that the study did not achieve the target sample size for efficacy assessment (n = 1000).