Ignite Creation Date:
2024-05-06 @ 3:18 PM
Last Modification Date:
2024-10-26 @ 1:46 PM
Study NCT ID:
NCT04581954
Status:
UNKNOWN
Last Update Posted:
2022-07-01
First Post:
2020-10-05
Brief Title:
Inflammatory Signal Inhibitors for COVID-19 MATIS
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
Randomised Multi-arm Trial of Ruxolitinib RUX and Fostamatinib FOS for COVID-19 Pneumonia
Status:
UNKNOWN
Status Verified Date:
2022-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MATIS
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 n171 57 per arm patients will be recruited in Stage 1 Following interim analysis to assess the efficacy and safety of the treatments approximately n285 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 JAKsignal 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 mildmoderate 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
Determine the efficacy of RUX or FOS to reduce mortality
Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation andor ECMO
Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation including CPAP or high flow nasal oxygen
Determine the efficacy of RUX or FOS to reduce the proportion of patients suffering clinically 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 COVID-19 pneumonia
Determine the efficacy of RUX and FOS to improve the severity of COVID19 pneumonia on a modified WHO COVID19 Ordinal Scale
Determine the efficacy of RUX or FOS to reduce the level of inflammatory biomarkers
Determine the efficacy of RUX or FOS to reduce blood ferritin CRP LDH and D-dimer
Determine the efficacy of RUX or FOS to reduce the level of serum creatinine
Determine the efficacy of RUX or FOS to reduce duration of hospital admission
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 JAKsignal 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 mildmoderate 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
Determine the efficacy of RUX or FOS to reduce mortality
Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation andor ECMO
Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation including CPAP or high flow nasal oxygen
Determine the efficacy of RUX or FOS to reduce the proportion of patients suffering clinically 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 COVID-19 pneumonia
Determine the efficacy of RUX and FOS to improve the severity of COVID19 pneumonia on a modified WHO COVID19 Ordinal Scale
Determine the efficacy of RUX or FOS to reduce the level of inflammatory biomarkers
Determine the efficacy of RUX or FOS to reduce blood ferritin CRP LDH and D-dimer
Determine the efficacy of RUX or FOS to reduce the level of serum creatinine
Determine the efficacy of RUX or FOS to reduce duration of hospital admission
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-001750-22 | EUDRACT_NUMBER | None | None |