Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Abstract

Importance:

Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.

Objective:

To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.

Design, Setting, and Participants:

Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021.

Interventions:

Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529).

Main Outcomes and Measures:

The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.

Results:

Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).

Conclusions and Relevance:

Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown.

Trial Registration:

ClinicalTrials.gov Identifier: NCT04545060.

• Authors: Anil Gupta, Yaneicy Gonzalez-Rojas, Erick Juarez, Manuel Crespo Casal, Jaynier Moya, Diego Rodrigues Falci, Elias Sarkis, Joel Solis, Hanzhe Zheng, Nicola Scott, Andrea L Cathcart, Sergio Parra, Jennifer E Sager, Daren Austin, Amanda Peppercorn, Elizabeth Alexander, Wendy W Yeh, Cynthia Brinson, Melissa Aldinger, Adrienne E Shapiro, COMET-ICE Investigators
• Journal: JAMA (JAMA) Vol. 327 Issue 13 Pg. 1236-1246 (04 05 2022) ISSN: 1538-3598 [Electronic] United States
• PMID: 35285853 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing
• Antiviral Agents
• sotrovimab

Topics

• Acute Disease
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Antibodies, Neutralizing (administration & dosage, therapeutic use)
• Antiviral Agents (administration & dosage, therapeutic use)
• COVID-19 (mortality)
• Disease Progression
• Hospitalization
• Humans
• Infusions, Intravenous
• Middle Aged
• Respiration, Artificial
• SARS-CoV-2
• Treatment Outcome
• COVID-19 Drug Treatment