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All Studies   All Outcomes       

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Hall et al., The Lancet Respiratory Medicine, doi:10.1016/S2213-2600(23)00376-4, TACTIC-R, NCT04390464
Dec 2023  
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Mortality, day 28 1% Improvement Relative Risk Mortality, day 14 -75% Death, mechanical ventila.. -53% Oxygen therapy -24% Discharge -3% Ravulizumab  TACTIC-R  LATE TREATMENT  RCT Is late treatment with ravulizumab beneficial for COVID-19? RCT 280 patients in the United Kingdom (May 2020 - May 2021) Higher progression (p=0.13) and higher oxygen therapy (p=0.57), not sig. c19early.org Hall et al., The Lancet Respiratory Me.., Dec 2023 Favorsravulizumab Favorscontrol 0 0.5 1 1.5 2+
RCT 417 hospitalized COVID-19 patients in the UK showing no significant difference in a composite primary endpoint (time to death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure) with baricitinib or ravulizumab. The trial was stopped early due to futility. There were no significant differences in secondary outcomes including disease severity, days to discharge, mortality, or adverse events.
risk of death, 1.0% lower, HR 0.99, p = 0.98, treatment 135, control 145, day 28.
risk of death, 75.0% higher, HR 1.75, p = 0.22, treatment 11 of 135 (8.1%), control 7 of 145 (4.8%), adjusted per study, multivariable, Cox proportional hazards, day 14.
death, mechanical ventilation, ECMO, cardiovascular organ support, renal failure, 53.0% higher, HR 1.53, p = 0.13, treatment 135, control 145, adjusted per study, multivariable, Cox proportional hazards, day 14.
risk of oxygen therapy, 24.0% higher, HR 1.24, p = 0.57, treatment 135, control 145, adjusted per study, multivariable, Cox proportional hazards, day 14.
risk of no hospital discharge, 3.1% higher, HR 1.03, p = 0.86, treatment 135, control 145, adjusted per study, inverted to make HR<1 favor treatment, multivariable, Cox proportional hazards, day 14.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hall et al., 31 Dec 2023, Randomized Controlled Trial, United Kingdom, peer-reviewed, 170 authors, study period 8 May, 2020 - 7 May, 2021, trial NCT04390464 (history) (TACTIC-R). Contact: fch22@medschl.cam.ac.uk.
This PaperRavulizumabAll
Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial
Frances C Hall, Joseph Cheriyan, Andrew P Cope, James Galloway, Ian Wilkinson, Simon Bond, Sam Norton, Edward Banham-Hall, Hannah Bayes, Michalis Kostapanos, Marianna Nodale, William G Petchey, Thomas Sheeran, Jonathan Underwood, David R Jayne, Group
Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1•11 (95% CI 0•62-1•99) for patients on baricitinib compared with standard of care alone, and 1•53 (0•88-2•67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation.
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Late treatment
is less effective
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