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.

NCT ID: NCT04953052

Last Updated: 2022-07-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-14
• Study Completion Date: 2022-11-30

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.

Conditions

Acute Respiratory Distress Syndrome; COVID-19 Acute Respiratory Distress Syndrome; Covid19; ARDS; Pulmonary Oedema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Imatinib Mesylate

Intervention Type: DRUG

An isotonic sterile solution of imatinib.

Intravenous Placebo

Intravenous Placebo matched solution- administered 25ml solution, twice daily over a two-hour infusion period

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

An isotonic sterile solution

Interventions

Imatinib Mesylate

An isotonic sterile solution of imatinib.

Intervention Type: DRUG

Placebo

An isotonic sterile solution

Intervention Type: DRUG

Other Intervention Names

Impentri

Eligibility Criteria

Inclusion Criteria

1. Male or female patients aged ≥18 years

2. Women of childbearing potential must have a negative serum pregnancy test to confirm eligibility

3. Provision of signed written informed consent from the patient or patient's legally acceptable representative

4. 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)

5. Meet Berlin definition for moderate - severe ARDS

1. Bilateral opacities - not fully explained by effusions, lobar/lung collapse, or nodules

2. Respiratory failure not fully explained by cardiac failure or fluid overload.

3. PaO2/FIO2 ≤200 mmHg with PEEP ≥5 cmH2O

6. Patient requires intubation or is currently intubated and has been for ≤48 hours

Exclusion Criteria

1. 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

2. Major trauma in the past 5 days

3. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year

4. 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

5. 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)

6. Patients considered inappropriate for critical care (e.g., being considered for palliative care)

7. Currently receiving extracorporeal membrane oxygenation (ECMO)

8. Severe chronic liver disease with Child-Pugh score >12 (Appendix 1)

9. White blood count <2.5 x 109/L; Hemoglobin <4.0 mmol/L (6.5g/dL); Platelets <50 x 109/L

10. ALT or AST >10x upper limit of normal (ULN) or bilirubin >3x ULN

11. Women who are pregnant or breast-feeding

12. Use of drugs with strong CYP3A4 induction potential, such as carbamazepine, efavirenz, enzalutamide, phenobarbital, phenytoin, hypericum, mitotane, nevirapine, primidone, rifabutin and rifampicin

13. Inability of the ICU staff to initiate administration of study treatment within 48 hours of intubation

14. Enrolled in a concomitant clinical trial of an investigational medicinal product

15. In the opinion of the investigator, progression to death is highly probable, irrespective of the provision of treatments

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exvastat Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary Burgess, MD

Role: STUDY_DIRECTOR

Exvastat Ltd.

Locations

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

Countries

India

Other Identifiers

959310

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EX003

Identifier Type: -

Identifier Source: org_study_id