Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.
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2023-07
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Abstract
Importance
Immune dysregulation contributes to poorer outcomes in COVID-19.Objective
To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.Design, setting, and participants
Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021.Interventions
Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day).Main outcomes and measures
The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale.Results
Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies.Conclusions and relevance
Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.Trial registration
ClinicalTrials.gov Identifier: NCT04593940.Type
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Publication Info
O'Halloran, Jane A, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W McCarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, et al. (2023). Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA, 330(4). pp. 328–339. 10.1001/jama.2023.11043 Retrieved from https://hdl.handle.net/10161/31115.
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Scholars@Duke
Emily Ray Ko
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for infectious disease.
Phillip Brian Smith
Dr. Smith completed his residency in pediatrics and a fellowship in neonatal medicine at Duke University Medical Center in 2004 and 2007, respectively. He completed an MHS in clinical research from Duke University in 2006 and an MPH in biostatistics from the University of North Carolina at Chapel Hill in 2009. His research is focused on pediatric drug safety, neonatal pharmacology, and the epidemiology of neonatal infections. Dr. Smith is or has been the protocol chair for more than 14 studies of drugs in infants and children. He is the Principal Investigator for the Environmental Influences on Child Health Outcomes (ECHO) Coordinating Center.
Cameron Robert Wolfe
HIV infection, Transplant-related infectious diseases, general infectious diseases, Biological and Emergency Preparedness for hospital systems, influenza and respiratory viral pathogens
Tatyana Der
Sean Michael O'Brien
Statistical methods for healthcare provider profiling; observational studies; Bayesian data analysis.
Hussein Rashid Al-Khalidi
My research interest includes design and analysis of cardiovascular clinical trials, medical devices, survival analysis, group-sequential analysis, time-to-recurrent or multiple events, continuous-time Markov models, stochastic process, linear model, dose-response modeling, design of experiments and adaptive designs.
Daniel Kelly Benjamin
Dr. Danny Benjamin is the Principal Investigator and Chair of the National Institute of Child Health and Human Development’s Pediatric Trials Network. The Network is responsible for designing and leading clinical trials of off-patent medicines in children of all ages across all therapeutic areas. The team has established, or is actively studying, the correct dosing and safety of more than 100 of the most commonly used medicines in children. These trials are conducted under an Investigational New Drug (IND) application with guidance from the Food and Drug Administration for labeling.
The Pediatric Trials Network has directly impacted the healthcare of over 90% of American children.
Signature programs of the Network include clinical trials in premature, term infants, breast feeding mothers, and obese children. Over the past 10 years, Danny’s group has enrolled more premature infants, at more sites, in more clinical trials of off-patent anti-infectives under an IND than all other academic medical centers, pharmaceutical companies, and government agencies in the world, combined.
Danny is recognized by the National Institutes of Health as a premiere mentor and educator. His research program serves as a platform to train students and early career investigators. Danny’s group has a clinical research summer program for high school, college graduate school, and medical students that recruits and mentors ~30 students each academic year. He has been the primary or secondary mentor for 10 faculty who have received career development awards and who have then gone on to establish their own independent research programs; six of whom are now Distinguished Professors.
Danny's service to the community is expressed through his passion for coaching baseball. He has coached over 1,000 recreation league, travel league, and scholastic baseball games. He is the head coach for Smith Middle School Baseball, perennially southern conference champions. Danny and his wife own a charitable non-profit that provides athletic and fitness opportunities for disadvantaged and special-needs school-aged boys and girls.
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