A Randomized Study to Investigate the Effect of Intravenous Imatinib on the Amount of Oxygen in the Lungs and Blood of Adults With COVID-19 Needing Mechanical Ventilation and Supportive Care. (IMPRESS COVID)
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|ClinicalTrials.gov Identifier: NCT04953052|
Recruitment Status : Withdrawn (Number of moderate to severe ARDS patients hospitalised due to COVID19 diminishingly small. Not expected to recruit required minimum number of patients.)
First Posted : July 7, 2021
Last Update Posted : July 28, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Respiratory Distress Syndrome COVID-19 Acute Respiratory Distress Syndrome Covid19 ARDS Pulmonary Oedema||Drug: Imatinib Mesylate Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Randomized, Double-blind, Multicentre 2-arm, Parallel-group, Placebo-controlled Study to Investigate the Efficacy and Safety of Intravenous Imatinib Mesylate in Reducing the Severity of Hypoxemic Respiratory Failure in Patients With Critical COVID-19 Receiving Standard of Care.|
|Estimated Study Start Date :||October 14, 2021|
|Estimated Primary Completion Date :||August 31, 2022|
|Estimated Study Completion Date :||November 30, 2022|
Experimental: Intravenous Imatinib Mesylate
Intravenous Imatinib Mesylate solution- 200mg as an 8mg/ml solution, administered twice daily (400mg total daily dose). Each dose administered in a 25ml solution over a two-hour infusion period.
Drug: Imatinib Mesylate
An isotonic sterile solution of imatinib.
Other Name: Impentri
Placebo Comparator: Intravenous Placebo
Intravenous Placebo matched solution- administered 25ml solution, twice daily over a two-hour infusion period
An isotonic sterile solution
- Change from baseline in Oxygen Saturation Index (OSI) at Day 10 [ Time Frame: From Baseline to Day 10 ]Oxygen saturation is a calculation derived from [mean airway pressure × FiO2 × 100] / SpO2.
- Change from Baseline in Oxygen Saturation Index (OSI) at Day 3 and Day 5 [ Time Frame: From Baseline to Day 3 and from baseline to Day 5 ]Oxygen saturation measured by pulse oximetry
- Mortality rate at Day 29 and Day 60 [ Time Frame: Day 29 and Day 60 ]Mortality at Day 29 and Day 60
- Change from baseline in WHO 9-point ordinal scale for clinical improvement to Day 10 and Day 29 [ Time Frame: The WHO ordinal scale will be recorded Days 1-10 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.
- Duration of mechanical ventilation (Days) to Day 29 and Day 60 [ Time Frame: To Day 29 and to Day 60 ]Number of days requiring to be on mechanical ventilation
- Duration of stay in ICU (Days) to Day 29 and Day 60 [ Time Frame: To Day 29 and to Day 60 ]Number of days within the ICU
- Time to first successful extubation (Hours) to Day 29 [ Time Frame: To Day 29 ]Number of hours to extubation (removal of the endotracheal tube)
- Number of days free of mechanical ventilation and survival (VFDsurv) at Day 29 and Day 60 [ Time Frame: At Day 29 and Day 60 ]Amongst survivors, the number of days free from mechanical ventilation
- Safety- Type, frequency, severity, and relationship to study treatment of any AEs, SAEs or AEs leading to discontinuation of study treatment from Day 1 to Day 29 (final follow up visit) [ Time Frame: Day 1 to Day 29 ]Safety adverse events and serious adverse event collection
- Incidence of related Treatment-Emergent Adverse Events- Tolerability [ Time Frame: Day 1 to Day 29 ]Tolerability
- Pharmacokinetic- Imatinib plasma concentration [ Time Frame: 4 samples collected Day 1, and single samples collected Days 3 and 5 ]Imatinib plasma concentration- Multivariate hierarchical analysis will be performed on various factors (age, sex, weight, height,appha-1-acid glycoprotein, haemoglobin, ALAT, CRP, eGFR, albumin, smoking, and concomitant drugs) to explore sources of variability in patient outcome. Significant predictors will be used as covariates to improve the performance of the PK model.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04953052
|Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda, Jail Road Indira Avenue)Anandpura|
|Vadodara, Gujarat, India, 390001|
|St George's Hospital, P D Mello Road, Fort Road, CST Terminal,|
|Mumbai, Maharashtra, India, 400001|
|Government Medical College and Hospital|
|Nagpur, Maharashtra, India, 440003|
|PCMC PGI Yashwantrao Chavan Memorial Hospital|
|Nagar, Pune, India, 411018|
|NRS Medical College and Hospital|
|Kolkata, West Bengal, India, 700014|
|Father Muller Hospital and Medical College|
|Mangalore, India, 575002|
|Mysuru, India, 570004|
|Indira Gandhi Government Medical College and Hospital|
|Nagpur, India, 440018|
|Study Director:||Gary Burgess, MD||Exvastat Ltd.|