Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial
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SciScore for 10.1101/2021.06.02.21258204: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The trial was approved by the East Midlands-Nottingham 2 Research Ethics Committee (20/EM/0115) and given national Urgent Public Health Status.
Consent: 19 Written informed consent was obtained from all patients with capacity.Sex as a biological variable Exclusion criteria included planned palliative care, pregnancy or breastfeeding, women of childbearing potential and non-vasectomised men who were unwilling to use effective contraception for the duration of the trial and throughout the drug-defined post-trial period, known HIV or chronic hepatitis B or C infection, concurrent immunosuppression with biological agents, a history of haematopoietic stem cell or solid organ transplant, … SciScore for 10.1101/2021.06.02.21258204: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The trial was approved by the East Midlands-Nottingham 2 Research Ethics Committee (20/EM/0115) and given national Urgent Public Health Status.
Consent: 19 Written informed consent was obtained from all patients with capacity.Sex as a biological variable Exclusion criteria included planned palliative care, pregnancy or breastfeeding, women of childbearing potential and non-vasectomised men who were unwilling to use effective contraception for the duration of the trial and throughout the drug-defined post-trial period, known HIV or chronic hepatitis B or C infection, concurrent immunosuppression with biological agents, a history of haematopoietic stem cell or solid organ transplant, known hypersensitivity to drug products or excipients, tuberculosis or other severe infections such as (non-SARS-CoV-2) sepsis, abscesses, and opportunistic infections requiring treatment, moderate or severe heart failure (NYHA class III/IV), or any other indication or medical history, that in the opinion of the patient’s local investigator, made the patient unsuitable for trial participation. Randomization Study design: The CATALYST trial is a randomised, open label, phase 2, multi-arm proof-of-concept trial. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:One previous non-randomised study of infliximab suggested potential efficacy, albeit with significant limitations including small sample size, use of historical controls, and being conducted prior to routine use of corticosteroids.26 This, together with circumstantial data, justified our inclusion of infliximab.18 However, although TNF inhibitors are widely used in inflammatory diseases, not all IMID are responsive, and TNF itself may suppress certain pro-inflammatory factors that may be relevant to COVID-19 such as type 1 interferon expression and Th17 cell differentiation.27 Inhibition of such cross-regulatory effects may underlie our negative findings, or simply indicate that TNF is not on a critical path to driving inflammatory responses as measured by CRP in patients hospitalised with COVID-19. GM-CSF inhibition might also have an additional benefit in retarding neutrophil recruitment and activation that may be of importance in the pathogenesis of severe COVID-19 and acute respiratory distress syndrome.28 Our safety data suggest that the lack of response to infliximab is not due to an increase in secondary infections. Whilst we cannot exclude the possibility of benefit being seen in a subset of patients or in larger studies, the clear divergence in primary outcome is broadly reflected in the secondary clinical findings and justifies the prioritisation of GM-CSF inhibition over TNF inhibition for further study in hospitalised COVID-19 patients. GM-CSF has an important rol...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title ISRCTN40580903 NA NA Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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