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

Introduction

Severe 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 analysis

The 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 <underline>></underline>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 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 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 number

EudraCT Number: 2020-001684-89

ISRCTN Number: 40580903

Strengths and limitations of this trial

• CATALYST will provide a rapid readout on the safety and proof-of-concept of candidate novel treatments

• CATALYST will enable phase III trial resources to be focussed and allocated for agents with a high likelihood of success

• CATALYST 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

• CATALYST is not designed to provide a definitive signal on clinical outcomes