Multi-arm trial of Inflammatory Signal Inhibitors 
for COVID-19 (MATIS) 

COVID-19 pneumonia is characterised by respiratory and multi-organ failure in the context of marked systemic inflammation. A number of therapeutic interventions targeting inflammatory signalling might reduce the severity of the inflammatory response phase resulting in amelioration of the lung damage thereby averting respiratory failure and the need for mechanical ventilation.

MATIS is a multi-site, two stage, open label, randomized (1:1:1) controlled trial to evaluate the efficacy of two inflammatory signal inhibitors, ruxolitinib (RUX) and fostamatinib (FOS), compared to standard of care (SOC) in the treatment of COVID-19 pneumonia. Adults hospitalised with mild COVID pneumonia defined by a modified WHO COVID-19 Ordinal Score of 3 (no oxygen therapy) or 4 (oxygen by mask or nasal prongs) were eligible for inclusion.

Outcome assessment and laboratory markers were recorded at Days one, seven, fourteen and twenty eight. 
The primary objective of MATIS is to determine the efficacy of RUX and FOS compared to SOC to reduce the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia at Day 14 following randomisation.

Severe COVID-19 pneumonia is defined as by a modified WHO COVID-19 Ordinal Score ≥5, defined by the following indicators of disease severity:

• Death OR
• Requirement for invasive ventilation (with or without organ support) OR
• Requirement for non-invasive ventilation including CPAP or 
  high flow oxygen OR
• O2 saturation less than 90% on 60% inspired oxygen

The primary outcome is analysed using a binomial regression model adjusting for age, baseline COVID-19 severity, COVID vaccination status and receipt of known effective treatments, namely (steroids and IL6-inhibitors).

Secondary outcomes of interest include each of these severity indicators separately, the need for organ support, length of hospital stay, serious adverse events, treatment discontinuation, change in inflammatory markers and serum creatinine, change in the pneumonia severity on the modified WHO COVID-19 Ordinal Score and readmission rates.

Stage One of this study aimed to randomised 171, with 57 participants in each arm. If at least one experimental intervention showed promise at interim Stage One analysis, then Stage Two intended to recruit a further 95 participants per arm.