{
  "abstract": "Objectives To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.Design Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage).Setting Five hospitals in England between October 2020 and September 2022.Participants Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4.Interventions Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC.Main outcome measures Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs).Results At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only.Conclusions We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hospital admission. Due to early stopping, the trial was underpowered to establish RUX’s effect in this population. Further study is needed.Trial registration number NCT04581954; EUDRA-CT: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001750-22/GB.",
  "authors": [
    {
      "affiliations": [
        "Imperial College Clinical Trials Unit, Imperial College London, London, UK"
      ],
      "name": "Lorna Hazell"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Clio Pillay"
    },
    {
      "affiliations": [
        "Imperial College Clinical Trials Unit, Imperial College London, London, UK"
      ],
      "name": "Victoria Cornelius"
    },
    {
      "affiliations": [
        "Imperial College Clinical Trials Unit, Imperial College London, London, UK"
      ],
      "name": "Rachel Phillips"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Asad Charania"
    },
    {
      "affiliations": [
        "Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "James Wason"
    },
    {
      "affiliations": [
        "Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Svetlana Cherlin"
    },
    {
      "affiliations": [
        "Immunology, Leeds Teaching Hospitals NHS Trust, Leeds, UK",
        "University of Leeds, Leeds, West Yorkshire, UK"
      ],
      "name": "Sinisa Savic"
    },
    {
      "affiliations": [
        "Infectious Diseases and Acute Medicine, Northwick Park Hospital, Harrow, London, UK"
      ],
      "name": "Ashley Whittington"
    },
    {
      "affiliations": [
        "Haemato-Oncology, Royal Berkshire NHS Foundation Trust, Reading, UK"
      ],
      "name": "Pratap Neelakantan"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"
      ],
      "name": "Paul Collini"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Lucy Cook"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Michelle Willicome"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Dragana Milojkovic"
    },
    {
      "affiliations": [
        "Respiratory Medicine, Imperial College Healthcare NHS Trust, London, London, UK",
        "National Heart and Lung Institute, Imperial College London, London, London, UK"
      ],
      "name": "Onn Min Kon"
    },
    {
      "affiliations": [
        "Imperial College Healthcare NHS Trust, London, UK",
        "National Heart and Lung Institute, Imperial College London, London, London, UK"
      ],
      "name": "Taryn Youngstein"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Andrew Innes"
    },
    {
      "affiliations": [
        "Imperial College Healthcare NHS Trust, London, UK",
        "Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK"
      ],
      "name": "Mark Thursz"
    },
    {
      "affiliations": [
        "Imperial College Healthcare NHS Trust, London, UK",
        "Department of Infectious Diseases, Imperial College London, London, UK"
      ],
      "name": "Graham S Cooke"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Nikhil Vergis"
    },
    {
      "affiliations": [
        "Department of Immunology and Inflammation, Imperial College London, London, UK",
        "Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Nichola Cooper"
    }
  ],
  "title": "Multiarm multistage randomised controlled trial of inflammatory signal inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic",
  "uid": "e0fc01d5-0635-5152-8406-634c2f354cc8"
}