Multi-arm multi-stage randomised controlled trial of Inflammatory Signal Inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic
File(s)
Published version
Author(s)
Hazell, Lorna
Cooper, Nichola
Type
Journal Article
Abstract
Objectives: To determine the safety and efficacy of ruxolitinib and fostamatinib compared to standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.
Design: Adaptive multi-arm, multi-stage, randomised, open label trial (3-arm, 2-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 World Health Organisation (WHO) COVID-19 severity grade of 3 or 4.
Interventions: Participants were randomly assigned 1:1:1 to receive ruxolitinib (10mg bd for 7 days then 5mg bd for 7 days), fostamatinib (150mg bd for 7 days then 100mg bd 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 (SAE).
Results: At Stage 1, 181 patients were randomised, with 4 assessed as ineligible post-randomisation. Fostamatinib was stopped early for futility with 16 participants (27.6%, N=58) developing severe COVID-19 pneumonia compared to 15 (25.0%, N=60) in the SOC arm (adjusted odds ratio (aOR) compared to SOC: 1.12; 95% confidence interval (CI): 0.49 to 2.58; p=0.608). Ruxolitinib 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 ruxolitinib arm compared to 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 fostamatinib arm, none in the ruxolitinib arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported serious adverse event and were numerically higher in the fostamatinib (10, 17.2%) and ruxolitinib (10, 16.1%) arms compared to SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the ruxolitinib arm only.
Conclusions: We found no evidence that fostamatinib 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 ruxolitinib’s effect in this population. Further study is needed.
Trial registration: NCT04581954; EUDRA-CT: 2020-001750-22
Design: Adaptive multi-arm, multi-stage, randomised, open label trial (3-arm, 2-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 World Health Organisation (WHO) COVID-19 severity grade of 3 or 4.
Interventions: Participants were randomly assigned 1:1:1 to receive ruxolitinib (10mg bd for 7 days then 5mg bd for 7 days), fostamatinib (150mg bd for 7 days then 100mg bd 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 (SAE).
Results: At Stage 1, 181 patients were randomised, with 4 assessed as ineligible post-randomisation. Fostamatinib was stopped early for futility with 16 participants (27.6%, N=58) developing severe COVID-19 pneumonia compared to 15 (25.0%, N=60) in the SOC arm (adjusted odds ratio (aOR) compared to SOC: 1.12; 95% confidence interval (CI): 0.49 to 2.58; p=0.608). Ruxolitinib 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 ruxolitinib arm compared to 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 fostamatinib arm, none in the ruxolitinib arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported serious adverse event and were numerically higher in the fostamatinib (10, 17.2%) and ruxolitinib (10, 16.1%) arms compared to SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the ruxolitinib arm only.
Conclusions: We found no evidence that fostamatinib 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 ruxolitinib’s effect in this population. Further study is needed.
Trial registration: NCT04581954; EUDRA-CT: 2020-001750-22
Date Issued
2026-02-05
Date Acceptance
2025-12-18
Citation
BMJ Open, 2026, 16 (2)
ISSN
2044-6055
Publisher
BMJ Publishing Group
Journal / Book Title
BMJ Open
Volume
16
Issue
2
Copyright Statement
© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1136/bmjopen-2025-100583
Publication Status
Published
Article Number
100583
Date Publish Online
2026-02-05