CATALYST trial protocol: A multicentre, open label, phase II, multi arm trial for an early and accelerated evaluation of the potential treatments for COVID 19 in hospitalised adults
IntroductionSevere SARS CoV 2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, pro inflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs. Methods and analysisThe CATALYST trial is a multi arm, open label, multi centre, 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 polymerase chain reaction (RT 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 disseminationThe 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 05 May 2020, current protocol version (v6.0) approval on 12 Oct 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 numberEudraCT Number: 2020 001684 89 ISRCTN Number: 40580903 Strengths and limitations of this trialO_LICATALYST will provide a rapid readout on the safety and proof of concept of candidate novel treatments C_LIO_LICATALYST will enable phase III trial resources to be focussed and allocated for agents with a high likelihood of success C_LIO_LICATALYST uses Bayesian multi level models to allow for nesting of repeated measures data, with factors for each individual patient and treatment arm, and allowing for non linear responses C_LIO_LICATALYST is not designed to provide a definitive signal on clinical outcomes C_LI
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