1. There was no statistically significant difference in recovery time in patients with COVID-19 pneumonia using treatment with abatacept, cenicriviroc, or infliximab compared to standard care.
2. Safety assessment endpoints showed no significant difference between the trial drugs and placebo, as both groups had a similar incidence of serious adverse events (SAE).
Evidence Rating Level: 1 (Excellent)
Study Rundown: This research study aims to address the immunopathology of COVID-19, which involves irregular immune cell function and cytokine/chemokine network dysregulation. While dexamethasone has shown mortality benefits for hospitalized COVID-19 patients, there is still significant morbidity and mortality, leading to the evaluation of other therapeutic approaches. The study is part of the ACTIV-1 Immune Modulator master protocol, which assesses immunomodulatory agents in hospitalized patients with moderate/severe COVID-19. Specifically, the study examines the effects of abatacept, cenicriviroc, and infliximab, which have unique mechanisms of action and in vitro efficacy against SARS-CoV-2, in conjunction with standard care for COVID-19 pneumonia. This randomized control trial found that hospitalized patients with COVID-19 pneumonia did not experience significantly different times to recovery for abatacept, cenicriviroc, or infliximab compared to placebo. One limitation is that COVID-19 vaccines became available during the study, but data was not collected regarding the patient’s vaccination status. Without this information, it becomes challenging to interpret the results accurately and understand the true efficacy of the immunomodulatory agents in the context of a vaccinated population. In conclusion, this study explores the value of immunomodulatory agents for patients with COVID-19 pneumonia and comments on the difficulty of choosing a primary endpoint for studies related to COVID-19 conducted in a dynamically evolving clinical landscape.
Click to read the study in JAMA
Click to read an accompanying editorial in JAMA
Relevant Reading: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): Designing Master Protocols for Evaluation of Candidate COVID-19 Therapeutics
In-Depth [randomized controlled trial]: This study was a randomized, double-masked, placebo-controlled master protocol clinical trial that included 1971 participants randomized at 95 hospitals between October 16, 2020 and December 31, 2021, using the ACTIV-1 master protocol. Participants eligible to be included in this study included adults aged 18 years or older with confirmed SARS-CoV-2 infection within 14 days, expected to be hospitalized for at least 72 hours, and showing signs of pulmonary involvement. The primary outcome was the median time to recovery by day 28, measured by the recovery rate ratio (RRR). Secondary outcomes included clinical status, mortality, and safety assessments. There was no significant difference in the primary endpoint, which measured the time to recovery from COVID-19 pneumonia for abatacept (RRR,1.12 [95% CI, 0.98-1.28]; P = 0.09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = 0.94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = 0.08) compared with standard care. Safety assessment endpoints showed no significant difference between the placebo and abatacept (risk difference, −1.7% [95% CI, −7.5% to 4.1%]), cenicriviroc (risk difference, 3.0% [95% CI, −4% to 10%]), and infliximab (risk difference, −0.8% [95% CI, −6.6% to 4.9%]).
Image: PD
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