Back to resultsA 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)
Primary Purpose
Acute Respiratory Distress Syndrome, COVID-19 Acute Respiratory Distress Syndrome, Covid19
Status
Withdrawn
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Imatinib Mesylate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring Acute Respiratory Distress Syndrome, ARDS, Covid-19, Imatinib, Oxygen Saturation Index, OSI, Endothelial Dysfunction, Pulmonary Oedema, Protein Kinase Inhibitor
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged ≥18 years
- Women of childbearing potential must have a negative serum pregnancy test to confirm eligibility
- Provision of signed written informed consent from the patient or patient's legally acceptable representative
- SARS-CoV-2 infection confirmed by RT-PCR laboratory test (which may include results from a test that was performed prior to hospital admission if, in the opinion of the Investigator, it is relevant to ongoing COVID-19)
Meet Berlin definition for moderate - severe ARDS
- Bilateral opacities - not fully explained by effusions, lobar/lung collapse, or nodules
- Respiratory failure not fully explained by cardiac failure or fluid overload.
- PaO2/FIO2 ≤200 mmHg with PEEP ≥5 cmH2O
- Patient requires intubation or is currently intubated and has been for ≤48 hours
Exclusion Criteria:
- Persistent septic shock (>24 hours) with a Mean Arterial Pressure (MAP) ≤65 mm Hg and serum lactate level >4 mmol/L (36 mg/dL) despite adequate volume resuscitation and vasopressor use (norepinephrine >0.2 μg/kg/min) for >6 hours
- Major trauma in the past 5 days
- Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year
- Pre-existing severe cardiopulmonary disease including, but not limited to, interstitial lung disease; severe COPD (GOLD Stage IV or FEV1<30% predicted); heart failure (estimated left ventricular ejection fraction < 40%); or a chronic lung condition requiring home oxygen treatment
- An underlying clinical condition that, in the opinion of the Investigator, would make it very unlikely for the patient to be successfully weaned from ventilation due to severe underlying diseases (e.g., severe malnutrition, severe neurological disease)
- Patients considered inappropriate for critical care (e.g., being considered for palliative care)
- Currently receiving extracorporeal membrane oxygenation (ECMO)
- Severe chronic liver disease with Child-Pugh score >12 (Appendix 1)
- White blood count <2.5 x 109/L; Hemoglobin <4.0 mmol/L (6.5g/dL); Platelets <50 x 109/L
- ALT or AST >10x upper limit of normal (ULN) or bilirubin >3x ULN
- Women who are pregnant or breast-feeding
- Use of drugs with strong CYP3A4 induction potential, such as carbamazepine, efavirenz, enzalutamide, phenobarbital, phenytoin, hypericum, mitotane, nevirapine, primidone, rifabutin and rifampicin
- Inability of the ICU staff to initiate administration of study treatment within 48 hours of intubation
- Enrolled in a concomitant clinical trial of an investigational medicinal product
- In the opinion of the investigator, progression to death is highly probable, irrespective of the provision of treatments
Sites / Locations
- Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda, Jail Road Indira Avenue)Anandpura
- St George's Hospital, P D Mello Road, Fort Road, CST Terminal,
- Government Medical College and Hospital
- PCMC PGI Yashwantrao Chavan Memorial Hospital
- NRS Medical College and Hospital
- Father Muller Hospital and Medical College
- JSS Hospital
- Indira Gandhi Government Medical College and Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intravenous Imatinib Mesylate
Intravenous Placebo
Arm Description
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.
Intravenous Placebo matched solution- administered 25ml solution, twice daily over a two-hour infusion period
Outcomes
Primary Outcome Measures
Change from baseline in Oxygen Saturation Index (OSI) at Day 10
Oxygen saturation is a calculation derived from [mean airway pressure × FiO2 × 100] / SpO2.
Secondary Outcome Measures
Change from Baseline in Oxygen Saturation Index (OSI) at Day 3 and Day 5
Oxygen saturation measured by pulse oximetry
Mortality rate at 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
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
Number of days requiring to be on mechanical ventilation
Duration of stay in ICU (Days) to Day 29 and Day 60
Number of days within the ICU
Time to first successful extubation (Hours) 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
Amongst survivors, the number of days free from mechanical ventilation
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04953052
Brief Title
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.
Acronym
IMPRESS COVID
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Number of moderate to severe ARDS patients hospitalised due to COVID19 diminishingly small. Not expected to recruit required minimum number of patients.
Study Start Date
October 14, 2021 (Anticipated)
Primary Completion Date
August 31, 2022 (Anticipated)
Study Completion Date
November 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Exvastat Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome, COVID-19 Acute Respiratory Distress Syndrome, Covid19, ARDS, Pulmonary Oedema
Keywords
Acute Respiratory Distress Syndrome, ARDS, Covid-19, Imatinib, Oxygen Saturation Index, OSI, Endothelial Dysfunction, Pulmonary Oedema, Protein Kinase Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous Imatinib Mesylate
Arm Type
Experimental
Arm Description
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.
Arm Title
Intravenous Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous Placebo matched solution- administered 25ml solution, twice daily over a two-hour infusion period
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate
Other Intervention Name(s)
Impentri
Intervention Description
An isotonic sterile solution of imatinib.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
An isotonic sterile solution
Primary Outcome Measure Information:
Title
Change from baseline in Oxygen Saturation Index (OSI) at Day 10
Description
Oxygen saturation is a calculation derived from [mean airway pressure × FiO2 × 100] / SpO2.
Time Frame
From Baseline to Day 10
Secondary Outcome Measure Information:
Title
Change from Baseline in Oxygen Saturation Index (OSI) at Day 3 and Day 5
Description
Oxygen saturation measured by pulse oximetry
Time Frame
From Baseline to Day 3 and from baseline to Day 5
Title
Mortality rate at Day 29 and Day 60
Description
Mortality at Day 29 and Day 60
Time Frame
Day 29 and Day 60
Title
Change from baseline in WHO 9-point ordinal scale for clinical improvement to Day 10 and Day 29
Description
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
Title
Duration of mechanical ventilation (Days) to Day 29 and Day 60
Description
Number of days requiring to be on mechanical ventilation
Time Frame
To Day 29 and to Day 60
Title
Duration of stay in ICU (Days) to Day 29 and Day 60
Description
Number of days within the ICU
Time Frame
To Day 29 and to Day 60
Title
Time to first successful extubation (Hours) to Day 29
Description
Number of hours to extubation (removal of the endotracheal tube)
Time Frame
To Day 29
Title
Number of days free of mechanical ventilation and survival (VFDsurv) at Day 29 and Day 60
Description
Amongst survivors, the number of days free from mechanical ventilation
Time Frame
At Day 29 and Day 60
Other Pre-specified Outcome Measures:
Title
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)
Description
Safety adverse events and serious adverse event collection
Time Frame
Day 1 to Day 29
Title
Incidence of related Treatment-Emergent Adverse Events- Tolerability
Description
Tolerability
Time Frame
Day 1 to Day 29
Title
Pharmacokinetic- Imatinib plasma concentration
Description
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.
Time Frame
4 samples collected Day 1, and single samples collected Days 3 and 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged ≥18 years
Women of childbearing potential must have a negative serum pregnancy test to confirm eligibility
Provision of signed written informed consent from the patient or patient's legally acceptable representative
SARS-CoV-2 infection confirmed by RT-PCR laboratory test (which may include results from a test that was performed prior to hospital admission if, in the opinion of the Investigator, it is relevant to ongoing COVID-19)
Meet Berlin definition for moderate - severe ARDS
Bilateral opacities - not fully explained by effusions, lobar/lung collapse, or nodules
Respiratory failure not fully explained by cardiac failure or fluid overload.
PaO2/FIO2 ≤200 mmHg with PEEP ≥5 cmH2O
Patient requires intubation or is currently intubated and has been for ≤48 hours
Exclusion Criteria:
Persistent septic shock (>24 hours) with a Mean Arterial Pressure (MAP) ≤65 mm Hg and serum lactate level >4 mmol/L (36 mg/dL) despite adequate volume resuscitation and vasopressor use (norepinephrine >0.2 μg/kg/min) for >6 hours
Major trauma in the past 5 days
Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year
Pre-existing severe cardiopulmonary disease including, but not limited to, interstitial lung disease; severe COPD (GOLD Stage IV or FEV1<30% predicted); heart failure (estimated left ventricular ejection fraction < 40%); or a chronic lung condition requiring home oxygen treatment
An underlying clinical condition that, in the opinion of the Investigator, would make it very unlikely for the patient to be successfully weaned from ventilation due to severe underlying diseases (e.g., severe malnutrition, severe neurological disease)
Patients considered inappropriate for critical care (e.g., being considered for palliative care)
Currently receiving extracorporeal membrane oxygenation (ECMO)
Severe chronic liver disease with Child-Pugh score >12 (Appendix 1)
White blood count <2.5 x 109/L; Hemoglobin <4.0 mmol/L (6.5g/dL); Platelets <50 x 109/L
ALT or AST >10x upper limit of normal (ULN) or bilirubin >3x ULN
Women who are pregnant or breast-feeding
Use of drugs with strong CYP3A4 induction potential, such as carbamazepine, efavirenz, enzalutamide, phenobarbital, phenytoin, hypericum, mitotane, nevirapine, primidone, rifabutin and rifampicin
Inability of the ICU staff to initiate administration of study treatment within 48 hours of intubation
Enrolled in a concomitant clinical trial of an investigational medicinal product
In the opinion of the investigator, progression to death is highly probable, irrespective of the provision of treatments
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Burgess, MD
Organizational Affiliation
Exvastat Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda, Jail Road Indira Avenue)Anandpura
City
Vadodara
State/Province
Gujarat
ZIP/Postal Code
390001
Country
India
Facility Name
St George's Hospital, P D Mello Road, Fort Road, CST Terminal,
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400001
Country
India
Facility Name
Government Medical College and Hospital
City
Nagpur
State/Province
Maharashtra
ZIP/Postal Code
440003
Country
India
Facility Name
PCMC PGI Yashwantrao Chavan Memorial Hospital
City
Nagar
State/Province
Pune
ZIP/Postal Code
411018
Country
India
Facility Name
NRS Medical College and Hospital
City
Kolkata
State/Province
West Bengal
ZIP/Postal Code
700014
Country
India
Facility Name
Father Muller Hospital and Medical College
City
Mangalore
ZIP/Postal Code
575002
Country
India
Facility Name
JSS Hospital
City
Mysuru
ZIP/Postal Code
570004
Country
India
Facility Name
Indira Gandhi Government Medical College and Hospital
City
Nagpur
ZIP/Postal Code
440018
Country
India
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
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.
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