Lead Investigator: Gus Slotman, Inspira Health Network
Title of Proposal Research: IDENTIFYING TOCILIZUMAB-RESPONSIVE COVID-19 PATIENTS FROM COVACTA, EMPACTA, AND REMDACTA RANDOMIZED CLINICAL TRIAL PRE-RANDOMIZATION DATA
Vivli Data Request: 8342, 7444
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Discovering effective treatments of COVID-19 infection is vital. In the EMPACTA randomized clinical trial (RCT) (NCT04372186) and the COVACTA RCT (NCT04320615) and the REMDACTA (NCT04409262) RCTs tocilizumab, a monoclonal antibody against the interleukin-6 receptor, did not improve survival in hospitalized COVID-19 patients with pneumonia. These RCT failures may indicate that tocilizumab was not effective. However, alternatively non-specific clinical RCT entry criteria may have enrolled so many patients not responsive to tocilizumab’s IL-6 inhibition that its true treatment effects were blunted.
Hypothesis: The clinical definitions used as COVACTA, EMPACTA, and REMDACTA RCT entry criteria may have enrolled so many patients whose pathophysiology could not benefit from tocizumab that its true treatment effects were diluted to invisibility. Previously the SMART prognostic methodology identified 55% of the COVACTA tocilizumab RCT in COVID-19 among whom tocilizumab reduced mortality by over 14%, while in the other COVACTA patients, with placebo mortality 1/3 of that in the responder group, tocilizumab increased mortality by 16%. The present study proposes to determine whether or not similar cohorts exist in the REMDACTA and EMPACTA RCT’s and if the SMART predictive models are similar in these studies. If this investigation identifies such patients, then the predictive models generated and validated in the combined databases of the 3 RCTs can be used to match tocilizumab-responsive COVID-19 pneumonia patients with this life-saving treatment
Requested Studies:
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
(Note: Additional studies added as part of Data Request 8342)
A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04409262
Sponsor ID: WA42511
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04372186
Sponsor ID: ML42528