Lead Investigator: Gus Slotman, Inspira Health Network
Title of Proposal Research: Pre-Randomization Data Modeling to Identify COVID-19 Patients Among Whom Tocilizumab Reduced Mortality
Vivli Data Request: 7444
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Discovering effective treatments of COVID-19 infection is vital. The COVACTA randomized clinical trial (RCT) of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, a cytokine in the patient’s response to COVID-19, did not improve survival in hospitalized COVID-19 with pneumonia. Simultaneous with the COVACTA RCT, dexamethasone, a corticosteroid, reduced COVID-19 mortality in the RECOVERY RCT, and immediately became standard of care. While only 22% of COVACTA tocilizumab RCT patients received concomitant corticosteroids, 82% of the patients in the later RECOVERY group RCT of tocilizumab versus placebo in COVID-19 were on corticosteroids at randomization. Since tocilizumab improved COVID-19 survival in RECOVERY but not in COVACTA, it is not clear whether COVACTA failed because tocilizumab is not sufficient alone to reduce mortality in severe COVID-19 infection or if tocilizumab requires concomitant corticosteroids or if tocilizumab was tested in patients who were physiologically unable to benefit from it.
Hypothesis: The clinical definitions used as COVACTA tocilizumab RCT entry criteria enrolled so many patients whose pathophysiology could not benefit from the study drug that its true treatment effects were diluted to invisibiity. The present study proposes to determine whether or not it is possible to predict from pre-randomization COVACTA RCT data which COVID-19 patients not receiving concomitant steroids were able to benefit from tocilizumab. If this investigation identifies such patients within COVACTA tocilizumab in COVID-19, then the predictive models generated can be used to match tocilizumab-responsive COVID-19 pneumonia patients with this life-saving treatment, independent of corticosteroids status.
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Severe COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04320615
Sponsor ID: WA42380