CATALYST trial protocol: a multicentre, open-label, phase II, multiarm trial for an early and accelerated evaluation of the potential treatments for COVID-19 in hospitalised adults

  1. Tonny Veenith
  2. Benjamin A. Fisher
  3. Daniel Slade
  4. Anna Rowe
  5. Rowena Sharpe
  6. David R. Thickett
  7. Tony Whitehouse
  8. Matthew Rowland
  9. James Scriven
  10. Dhruv Parekh
  11. Sarah J. Bowden
  12. Joshua S. Savage
  13. Duncan Richards
  14. Julian Bion
  15. Pamela Kearns
  16. Simon Gates

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Abstract

Severe SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, proinflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs.

Methods and analysis

The CATALYST trial is a multiarm, open-label, multicentre, phase II platform trial designed to identify candidate novel treatments to improve outcomes of patients hospitalised with COVID-19 compared with usual care. Treatments with evidence of biomarker improvements will be put forward for larger-scale testing by current national phase III platform trials. Hospitalised patients >16 years with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription PCR assay) and a C reactive protein (CRP) ≥40 mg/L are eligible. The primary outcome measure is CRP, measured serially from admission to day 14, hospital discharge or death. Secondary outcomes include the WHO Clinical Progression Improvement Scale as a principal efficacy assessment.

Ethics and dissemination

The protocol was approved by the East Midlands-Nottingham 2 Research Ethics Committee (20/EM/0115) and given urgent public health status; initial approval was received on 5 May 2020, current protocol version (V.6.0) approval on 12 October 2020. The MHRA also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration numbers

EudraCT2020-001684-89, NCT40580903 .

Article activity feed

  1. Version published to 10.1136/bmjopen-2021-050202
  2. ScreenIT

    SciScore for 10.1101/2021.02.10.21251478: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Informed consent is requested from patients with capacity by an investigator who has been delegated the responsibility on the delegation log.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableExclusion criteria include patient or personal/professional legal representative refusal, planned palliative care, pregnancy or breastfeeding women, women of childbearing potential and non-vasectomised men who are unwilling to use effective contraception for the duration of the trial and throughout the drug-defined post-trial period.

    Table 2: Resources

    Antibodies
    SentencesResources
    Initial candidate drugs included within the multi-arm design were namilumab, and infliximab, monoclonal antibodies targeting the pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α respectively.
    TNF-α
    suggested: None
    Namilumab is an anti-GM-CSF monoclonal antibody with a good safety profile up to phase II studies in rheumatoid arthritis (RA) and axial spondyloarthropathy with over 360 individuals dosed in total (15-18).
    anti-GM-CSF
    suggested: None
    Infliximab is a widely available anti-TNF alpha monoclonal antibody licensed for the treatment of a number of diseases including RA.
    anti-TNF
    suggested: None
    Software and Algorithms
    SentencesResources
    CATALYST will also be centrally monitored, which may trigger additional on-site monitoring.
    CATALYST
    suggested: (CATALYST, RRID:SCR_017127)

    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:
    Limitations of CRP, however, include lower utility for candidate therapeutics whose mechanism of action is not immunomodulation, and the diminished ability to assess drugs that directly target IL-6, due to the direct pharmacodynamics effects on CRP. This study was designed before use of IL-6 blockade outside of trials, and if tocilizumab were to be widely adopted, adaptive modification of the current trial design may be required to account for this. In conclusion, the major strength of CATALYST is its ability to provide a rapid readout on safety, and proof-of-efficacy enabling phase III trial resources to be focussed and allocated for drugs with a high likelihood of success (44, 48). This will reduce the time lag in translating early phase drugs into effective therapeutics for COVID-19.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    About SciScore

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  3. Version published to 10.1101/2021.02.10.21251478v1 on medRxiv