Inflammatory Signal Inhibitors for COVID-19 (MATIS) (MATIS)
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ClinicalTrials.gov Identifier: NCT04581954 |
Recruitment Status : Unknown
Verified June 2022 by Imperial College London.
Recruitment status was: Recruiting
First Posted : October 9, 2020
Last Update Posted : July 1, 2022
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Tracking Information | |||||||
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First Submitted Date ICMJE | October 5, 2020 | ||||||
First Posted Date ICMJE | October 9, 2020 | ||||||
Last Update Posted Date | July 1, 2022 | ||||||
Actual Study Start Date ICMJE | October 2, 2020 | ||||||
Estimated Primary Completion Date | June 30, 2022 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Inflammatory Signal Inhibitors for COVID-19 (MATIS) | ||||||
Official Title ICMJE | Randomised Multi-arm Trial of Ruxolitinib (RUX) and Fostamatinib (FOS) for COVID-19 Pneumonia | ||||||
Brief Summary | The Multi-arm trial of Inflammatory Signal Inhibitors for COVID-19 (MATIS) study is a two-stage, open-label, randomised controlled trial assessing the efficacy of ruxolitinib (RUX) and fostamatinib (FOS) individually, compared to standard of care in the treatment of COVID-19 pneumonia. The primary outcome is the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Patients are treated for 14 days and will receive follow-up assessment at 7, 14 and 28 days after the first study dose. Patients with mild or moderate COVID-19 pneumonia will be recruited. Initially, n=171 (57 per arm) patients will be recruited in Stage 1. Following interim analysis to assess the efficacy and safety of the treatments, approximately n=285 (95 per arm) will be recruited during Stage 2. | ||||||
Detailed Description | COVID-19 pneumonia is characterised by respiratory and multi-organ failure in the context of marked systemic inflammation. It is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV2) infection. The hallmark of severe disease is hypoxia and a radiological pattern of acute lung injury that shares features with Acute Respiratory Distress Syndrome (ARDS). Early features of COVID-19 result from host viral response and typically include symptoms such as fever and dry cough. Later features, typically occurring beyond 7 days, are characterised by marked and progressive systemic inflammation, identified by elevations in a plethora of inflammatory molecules such as C-reactive protein, ferritin and IL6. In a subset of patients, hyperinflammatory responses drive acute lung injury and may result in catastrophic multi-organ failure and death. The aetiology of COVID-19 induced ARDS is incompletely understood but appears to be associated with lung inflammation effected by a monocytic and neutrophilic infiltration, elevated cytokine levels and tissue damage. Elevations in circulating inflammatory molecules are associated with poor prognosis. In particular, the COVID-19 hyperinflammatory response syndrome is associated thrombotic complications which are postulated to drive cardiac dysfunction and microvascular thrombi, suggested by elevations in troponin and D-dimer, respectively. Similar hyperinflammatory responses are also seen in macrophage activation syndromes such as haemophagocytic lymphohistiocytosis, or in the cytokine release syndrome associated with chimeric antigen receptor T cell therapy. Further, preliminary data from China and Italy have shown immediate resolution of symptoms using anti-interleukin-6 agents (anti-IL6) therapy and Janus kinase inhibitors (JAK)/signal transducer and activator of transcription (STAT) inhibitors in patients with severe disease. There may be an early window of opportunity to treat the COVID-19 hyperinflammatory syndrome before acute lung injury leads to organ failure. There are currently no approved treatments for COVID-19 pneumonia. This is a protocol for a randomised controlled, multi-arm trial of early intervention with inflammatory signal inhibitors. Study purpose 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. This trial aims to evaluate the efficacy of two inhibitors of key signalling pathways using drugs which are already licensed for use in other clinical indications. Primary objective The primary objective is to determine the efficacy of RUX and FOS to reduce the proportion of hospitalised patients progressing from mild/moderate to severe COVID-19 pneumonia. A modified World Health Organization (WHO) COVID-19 Severity Ordinal Scale (COVID-19 Therapeutic Trial Synopsis published 18th February 2020) will be used to grade clinical deterioration from Hospitalised Mild Disease (<5) to Hospitalised Severe Disease (greater than or equal to 5). The modification includes an additional grade for Hospitalised Severe Disease that allows the capture of clinical deterioration in patients for whom escalation in organ support is not offered. Patients are eligible for recruitment to MATIS at grades 3 or 4. These patients stand to gain the greatest benefit from inflammatory signal inhibitors that may ameliorate the cytokine storm and prevent organ failure. Secondary objectives
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single (Outcomes Assessor) Primary Purpose: Treatment |
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Intervention ICMJE |
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Publications * | Vergis N, Phillips R, Cornelius V, Katsarou A, Youngstein T, Cook L, Willicombe M, Pilay C, Shturova T, Almonte M, Charania A, Turner R, Kon OM, Cooke G, Thursz M, Cherlin S, Wason J, Milojkovic D, Innes AJ, Cooper N. 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. Trials. 2021 Apr 12;22(1):270. doi: 10.1186/s13063-021-05190-z. | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Unknown status | ||||||
Estimated Enrollment ICMJE |
456 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | June 30, 2022 | ||||||
Estimated Primary Completion Date | June 30, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United Kingdom | ||||||
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Administrative Information | |||||||
NCT Number ICMJE | NCT04581954 | ||||||
Other Study ID Numbers ICMJE | 20HH5926 2020-001750-22 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Imperial College London | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Imperial College London | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
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Investigators ICMJE |
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PRS Account | Imperial College London | ||||||
Verification Date | June 2022 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |