Acute Respiratory Distress SyndromePhase 2IMPRESS COVIDNCT04953052
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.
A Phase 2 study testing Imatinib Mesylate in people with Acute Respiratory Distress Syndrome and COVID-19 Acute Respiratory Distress Syndrome, run by Exvastat Ltd. at 8 sites in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, COVID-19 Acute Respiratory Distress Syndrome, Covid19
- What is being tested?
- Imatinib Mesylate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 8 sitesIndia
- Study dates
- 14 Oct 2021to 30 Nov 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
India8 sites
NRS Medical College and Hospital
Kolkata, West Bengal, 700014
Father Muller Hospital and Medical College
Mangalore, 575002
St George's Hospital, P D Mello Road, Fort Road, CST Terminal,
Mumbai, Maharashtra, 400001
JSS Hospital
Mysuru, 570004
PCMC PGI Yashwantrao Chavan Memorial Hospital
Nagar, Pune, 411018
Government Medical College and Hospital
Nagpur, Maharashtra, 440003
Indira Gandhi Government Medical College and Hospital
Nagpur, 440018
Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda, Jail Road Indira Avenue)Anandpura
Vadodara, Gujarat, 390001
About this study
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.
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.
Read more
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.
- Conditions
- Acute Respiratory Distress Syndrome, COVID-19 Acute Respiratory Distress Syndrome, Covid19, ARDS, Pulmonary Oedema
- Being tested
- Imatinib Mesylate, Placebo
- Keywords
- Acute Respiratory Distress Syndrome, ARDS, Covid-19, Imatinib, Oxygen Saturation Index, OSI, Endothelial Dysfunction, Pulmonary Oedema, Protein Kinase Inhibitor
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19, Pulmonary Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib MesylateDrug
Also called Impentri
An isotonic sterile solution of imatinib.
PlaceboDrug
An isotonic sterile solution
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Imatinib Mesylate | Experimental | 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. Receives: Drug: Imatinib Mesylate |
| Intravenous Placebo | Placebo comparator | Intravenous Placebo matched solution- administered 25ml solution, twice daily over a two-hour infusion period Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Oxygen Saturation Index (OSI) at Day 10
Oxygen saturation is a calculation derived from [mean airway pressure × FiO2 × 100] / SpO2.
Measured: From Baseline to Day 10
Secondary outcomes (7)
Change from Baseline in Oxygen Saturation Index (OSI) at Day 3 and Day 5
Oxygen saturation measured by pulse oximetry
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: At Day 29 and Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2021
- Study start14 Oct 2021 (estimated)
- Primary completion31 Aug 2022 (estimated)
- Study completion30 Nov 2022 (estimated)
Why it stopped: Number of moderate to severe ARDS patients hospitalised due to COVID19 diminishingly small. Not expected to recruit required minimum number of patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exvastat Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gary Burgess, MD, Study director, Exvastat Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04953052
- Sponsor's protocol ID
- EX003
- Other IDs
- 959310
- Acronym
- IMPRESS COVID
- Status last verified
- Jul 2022
- First submitted
- 29 Jun 2021
- Last updated
- 28 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04953052
- Acronym / sponsor ID
- IMPRESS COVID / EX003
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Number of moderate to severe ARDS patients hospitalised due to COVID19 diminishingly small. Not expected to recruit required minimum number of patients.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Exvastat Ltd.Industry (pharma, biotech, devices)
- Study start
- 14 Oct 2021 (estimated)
- Primary completion
- 31 Aug 2022 (estimated)
- Study completion
- 30 Nov 2022 (estimated)
- First posted
- 7 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Imatinib Mesylate | Experimental | Drug: Imatinib MesylateIntravenous 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 | Placebo comparator | Drug: PlaceboIntravenous Placebo matched solution- administered 25ml solution, twice daily over a two-hour infusion period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib MesylateAlso: ImpentriAn isotonic sterile solution of imatinib. | Drug | Intravenous Imatinib Mesylate |
| PlaceboAn isotonic sterile solution | Drug | Intravenous Placebo |
Primary outcome
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.
7 secondary outcomes
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
Mortality rate 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
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
Time frame: To Day 29 and to Day 60
Duration of stay in ICU (Days) to Day 29 and Day 60
Time frame: To Day 29 and to Day 60
Time to first successful extubation (Hours) to Day 29
Time frame: To Day 29
Number of days free of mechanical ventilation and survival (VFDsurv) at Day 29 and Day 60
Time frame: At Day 29 and Day 60
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Burgess, MD study director
Exvastat Ltd.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib Mesylate in people with Acute Respiratory Distress Syndrome and COVID-19 Acute Respiratory Distress Syndrome, run by Exvastat Ltd. at 8 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in Oxygen Saturation Index (OSI) at Day 10 (time frame: From Baseline to Day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2022.