Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial

• Published in: Current controlled trials in cardiovascular medicine 2021-04, Vol.22 (1), p.270-270, Article 270
• Main Authors: Vergis, Nikhil, Phillips, Rachel, Cornelius, Victoria, Katsarou, Alexia, Youngstein, Taryn, Cook, Lucy, Willicombe, Michelle, Pilay, Clio, Shturova, Tina, Almonte, Melanie, Charania, Asad, Turner, Richard, Kon, Onn Min, Cooke, Graham, Thursz, Mark, Cherlin, Svetlana, Wason, James, Milojkovic, Dragana, Innes, Andew J, Cooper, Nichola
• Format: Article
• Language: English
• Subjects: Adult; Aminopyridines; Bacterial pneumonia; coronavirus; Coronaviruses; COVID-19; COVID-19 Drug Treatment; Drug dosages; Drug therapy; fostamatinib; Hospital patients; Humans; Letter; Morpholines; Nitriles; Oxazines - therapeutic use; Pandemics; Pneumonia; protocol; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Pyrimidines; randomised controlled trial; Randomized Controlled Trials as Topic; Respiration, Artificial; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism - prevention & control
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-021-05190-z

The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease CRP ≥ 30mg/L at any time point Informed consent from patient or personal or professional representative Agreement to abstain from sexual intercourse or use contraception that is >99% effective for all participants of childbearing potential for 42 days after the last dose of study drug. For male participants, agreement to abstain from sperm donation for 42 days after the last dose of study drug. Requiring either invasive or non-invasive ventilation including CPAP or high flow nasal oxygen at any point after hospital admission but before baseline, not