The COVID-19 pandemic has led to an increase in the number of patients admitted to intensive care units (ICU) with acute respiratory distress syndrome (ARDS). ARDS is a severe, life-threatening medical condition characterised by inflammation and fluid in the lungs. There is no proven therapy to reduce fluid leak, also known as pulmonary oedema, in ARDS. However, recent studies have discovered that imatinib prevents fluid leak in the lungs in inflammatory conditions, while leaving the immune response intact. Adding imatinib into the standard care package may, therefore, decrease mortality and reduce the duration of mechanical ventilation compared with standard care alone, in critically-ill patients with COVID-19. To help determine the impact of imatinib in these patients we present a randomised, double-blind, multi-centre, 2-arm, parallel-group, placebo-controlled clinical study of intravenous imatinib in 84 mechanically-ventilated, adult subjects with COVID-19-related ARDS. Study participants (patients who have consented into the study) will receive the study drug (imatinib or placebo) twice daily for a period of 10 days. The effect of the intervention will be tested by measuring the change from baseline in the Oxygen Saturation Index (OSI) at day 10. OSI is a non-invasive means of measuring oxygenation and is an independent predictor of mortality in patients with ARDS, serving thus as a relevant endpoint from which to assess the efficacy of imatinib. Other measurements will include regular blood tests as part of safety assessments. Time on ventilation and morbidity and mortality will be recorded as secondary outcome measures. Blood tests will also allow the investigation of the pharmacokinetic properties of imatinib, as well as biomarkers of inflammation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
An isotonic sterile solution of imatinib.
An isotonic sterile solution
Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda, Jail Road Indira Avenue)Anandpura
Vadodara, Gujarat, India
St George's Hospital, P D Mello Road, Fort Road, CST Terminal,
Mumbai, Maharashtra, India
Government Medical College and Hospital
Nagpur, Maharashtra, India
PCMC PGI Yashwantrao Chavan Memorial Hospital
Nagar, Pune, India
NRS Medical College and Hospital
Kolkata, West Bengal, India
Father Muller Hospital and Medical College
Mangalore, India
JSS Hospital
Mysuru, India
Indira Gandhi Government Medical College and Hospital
Nagpur, India
Change from baseline in Oxygen Saturation Index (OSI) at Day 10
Oxygen saturation is a calculation derived from \[mean airway pressure × FiO2 × 100\] / SpO2.
Time frame: From Baseline to Day 10
Change from Baseline in Oxygen Saturation Index (OSI) at Day 3 and Day 5
Oxygen saturation measured by pulse oximetry
Time frame: From Baseline to Day 3 and from baseline to Day 5
Mortality rate at Day 29 and Day 60
Mortality at Day 29 and Day 60
Time frame: Day 29 and Day 60
Change from baseline in WHO 9-point ordinal scale for clinical improvement to Day 10 and Day 29
The WHO Ordinal Scale for Clinical Improvement (0 to 8, where a higher value indicates worse outcome). It measures illness severity over time using the following categories: Uninfected, Ambulatory (no limitation of activities), Ambulatory (limitation of activities), Hospitalized (no O2 therapy), Hospitalized (O2 by nasal prongs or mask), Hospitalized (O2 by NIV or HFNO), Hospitalized (intubation and invasive mechanical ventilation), Hospitalized (ventilation and additional organ support \[vasopressors, CVVH, ECMO\]), Death.
Time frame: The WHO ordinal scale will be recorded Days 1-10 and Day 29
Duration of mechanical ventilation (Days) to Day 29 and Day 60
Number of days requiring to be on mechanical ventilation
Time frame: To Day 29 and to Day 60
Duration of stay in ICU (Days) to Day 29 and Day 60
Number of days within the ICU
Time frame: To Day 29 and to Day 60
Time to first successful extubation (Hours) to Day 29
Number of hours to extubation (removal of the endotracheal tube)
Time frame: To Day 29
Number of days free of mechanical ventilation and survival (VFDsurv) at Day 29 and Day 60
Amongst survivors, the number of days free from mechanical ventilation
Time frame: At Day 29 and Day 60
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