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Randomized Controlled Trial
. 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 #  1 , Clio Pillay #  2   3 , Victoria Cornelius  1 , Rachel Phillips  1 , Asad Charania  2   3 , James Wason  4 , Svetlana Cherlin  4 , Sinisa Savic  5   6 , Ashley Whittington  7 , Pratap Neelakantan  8 , Paul Collini  9 , Lucy Cook  2   3 , Michelle Willicome  2   3 , Dragana Milojkovic  2   3 , Onn Min Kon  10   11 , Taryn Youngstein  3   11 , Andrew Innes  2   3 , Mark Thursz  3   12 , Graham S Cooke  3   13 , Nikhil Vergis #  2   3 , Nichola Cooper #  14   3
Affiliations
Randomized Controlled Trial

Multiarm multistage randomised controlled trial of inflammatory signal inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic

Lorna Hazell et al. BMJ Open. .

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.

Keywords: COVID-19; Clinical Trial; Drug Therapy.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author). LH, CP, RP, AW, PN, PC, LC, MT and NV declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work. VC is a coinvestigator leading statistical design, methods and analysis for the MATIS trial, funded by Novartis and Rigel, is a committee member for the National Institute for Health and Care Research (NIHR) Academy Doctoral board, a DMEC member for the NIHR HTA-funded BAY Project. Behavioural Activation for young people with depression in specialist child and adolescent mental health services and is chair of the DMC for NIHR HTA-funded Research into Antipsychotic Discontinuation and Reductions. AC has been an employee of Roche since 2022. DM has received honorary payments from Novartis, Incyte and Ascentage Pharma, has participated on an advisory board for Ascentage Pharma and has received investigator-led institutional research funding from Incyte. MW has received honorary payments from AstraZeneca, has participated on an advisory board or data monitoring committee for Hansa Pharmaceuticals, received equipment, materials, drugs, medical writing, gifts or other services from Moderna and has had a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Hansa Pharmaceuticals. OMK has participated on an advisory board or data monitoring committee for the NIHR DILI study and has had team members funded by grants from Cepheid. GSC has participated in an end point review committee for Sanofi and is a board member for the MHRA. SS holds the Chair of British Society for Immunology-Clinical Immunology professional network. JW and SC have had team members funded by grants from Novartis and Rigel. TY is the recipient of a grant from UKRI MRC BHF Cardio-IMID Partnership, has received consulting fees for the Ad Board Abbvie 2024 and is Treasurer for the UK and Ireland Vasculitis and Rare Disease Group. AI has received consulting fees, honouraria for speakers’ bureaus, international travel support and/or personal fees from Novartis and Incyte. NC has received research grants from Novartis and Rigel for conducting MATIS, honouraria for consultancy from Novartis, Sobi, Sanofi, Amgen, Argenyx, research support from Novartis and Argenx and has funding from the NIHR Imperial Biomedical Research Centre.

Figures

Figure 1
Figure 1
Multi-Arm Trial of Inflammatory Signal Inhibitors for COVID-19 trial design.
Figure 2
Figure 2
Participant flow. SOC, standard of care.
Figure 3
Figure 3
Recruitment over time.
See this image and copyright information in PMC

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