tetano
Editor, Senior Moderator
BMJ Open
. 2026 Feb 5;16(2):e100583.
doi: 10.1136/bmjopen-2025-100583.
Multiarm multistage randomised controlled trial of inflammatory signal inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic
Lorna Hazell[SUP] #[/SUP][SUP] 1 [/SUP], Clio Pillay[SUP] #[/SUP][SUP] 2 3 [/SUP], Victoria Cornelius[SUP] 1 [/SUP], Rachel Phillips[SUP] 1 [/SUP], Asad Charania[SUP] 2 3 [/SUP], James Wason[SUP] 4 [/SUP], Svetlana Cherlin[SUP] 4 [/SUP], Sinisa Savic[SUP] 5 6 [/SUP], Ashley Whittington[SUP] 7 [/SUP], Pratap Neelakantan[SUP] 8 [/SUP], Paul Collini[SUP] 9 [/SUP], Lucy Cook[SUP] 2 3 [/SUP], Michelle Willicome[SUP] 2 3 [/SUP], Dragana Milojkovic[SUP] 2 3 [/SUP], Onn Min Kon[SUP] 10 11 [/SUP], Taryn Youngstein[SUP] 3 11 [/SUP], Andrew Innes[SUP] 2 3 [/SUP], Mark Thursz[SUP] 3 12 [/SUP], Graham S Cooke[SUP] 3 13 [/SUP], Nikhil Vergis[SUP] #[/SUP][SUP] 2 3 [/SUP], Nichola Cooper[SUP] #[/SUP][SUP] 14 3 [/SUP]
Affiliations
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.
Keywords: COVID-19; Clinical Trial; Drug Therapy.
. 2026 Feb 5;16(2):e100583.
doi: 10.1136/bmjopen-2025-100583.
Multiarm multistage randomised controlled trial of inflammatory signal inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic
Lorna Hazell[SUP] #[/SUP][SUP] 1 [/SUP], Clio Pillay[SUP] #[/SUP][SUP] 2 3 [/SUP], Victoria Cornelius[SUP] 1 [/SUP], Rachel Phillips[SUP] 1 [/SUP], Asad Charania[SUP] 2 3 [/SUP], James Wason[SUP] 4 [/SUP], Svetlana Cherlin[SUP] 4 [/SUP], Sinisa Savic[SUP] 5 6 [/SUP], Ashley Whittington[SUP] 7 [/SUP], Pratap Neelakantan[SUP] 8 [/SUP], Paul Collini[SUP] 9 [/SUP], Lucy Cook[SUP] 2 3 [/SUP], Michelle Willicome[SUP] 2 3 [/SUP], Dragana Milojkovic[SUP] 2 3 [/SUP], Onn Min Kon[SUP] 10 11 [/SUP], Taryn Youngstein[SUP] 3 11 [/SUP], Andrew Innes[SUP] 2 3 [/SUP], Mark Thursz[SUP] 3 12 [/SUP], Graham S Cooke[SUP] 3 13 [/SUP], Nikhil Vergis[SUP] #[/SUP][SUP] 2 3 [/SUP], Nichola Cooper[SUP] #[/SUP][SUP] 14 3 [/SUP]
Affiliations
- PMID: 41644167
- DOI: 10.1136/bmjopen-2025-100583
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.
Keywords: COVID-19; Clinical Trial; Drug Therapy.