The Safety & Efficacy of Imatinib for the Treatment of SARS-COV-2 Induced Pneumonia

Study Overview
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Brief Summary
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A randomized controlled pilot study on the safety & efficacy of imatinib for the treatment of patient with moderate to severe SARS-COV-2 induced pneumonia.

Detailed Description
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As the coronavirus disease (COVID-19) spreads worldwide, awaiting the development of a vaccine, researchers are looking among the arsenal of available drugs, for a potential cure or medication to improve patients' outcome. A highly elevated levels of cytokines in COVID-19 patients requiring ICU admission, has suggested that a cytokine storm was associated with disease severity. Data from cellular, animal models and clinical trials, showed a beneficial role of tyrosine kinase inhibitors in the regulation of inflammation, the maintenance of endothelial barrier integrity, as well as the expression of antiviral properties. This data is especially derived from imatinib, the most studied Abl family kinase inhibitor, that is currently in clinical use for multiple medical conditions. Based on this encouraging data, we hypothesize that imatinib might be beneficial for the treatment of patients with SARS-CoV-2 pneumonia, in the aim of preventing disease progression into the severe phenotype of hypoxic respiratory failure and acute respiratory distress syndrome.

Official Title
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Imatinib for the Treatment of SARS-COV-2 Induced Pneumonia: A Pilot Study

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Imatinib Mesylate
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with PCR positive for SARS-COV-2 Hospitalized with moderate to severe respiratory symptoms as assessed by the Egyptian Ministry of Health National Guidelines Informed consent explained & signed by patient or his 1st degree relatives or legally authorized representative. Exclusion Criteria: Pregnant women (or) breast feeding women Patients younger than 18 years of age Patients with known allergy to imatinib Total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) > 5x upper limit of normal (ULN). Creatinine clearance (CrCl) < 30 mL/minute. Patient already on mechanical ventilation at time of screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib Standard Dose<br>Imatinib 400 mg oral tablet once daily for 21 days In addition for the treatment for COVID-19 pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH). | Drug: Imatinib Mesylate<br>* Adding treatment by imatinib oral tablet into the standard treatment for moderate to severe COVID-19 pneumonia.<br>* Other names: Imatinib;|
| Experimental: Imatinib Low Dose<br>Imatinib 200 mg oral tablet once daily for 21 days. In addition to the treatment for COVID-19 Pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH). | Drug: Imatinib Mesylate<br>* Adding treatment by imatinib oral tablet into the standard treatment for moderate to severe COVID-19 pneumonia.<br>* Other names: Imatinib;|
| Active Comparator: Control<br>Treatment for COVID-19 pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH). | Drug: Standard of Care<br>* Standard of Care for the Moderate to Severe COVID-19 Pneumonia as per the Egyptian National Protocol by the Ministry of Health.<br>* Other names: Standard;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint: Disease Progression | Proportion of patients with COVID-19 pneumonia progressed to critical illness in need for invasive mechanical ventilation. | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Hypoxic Index | Improvement of Hypoxic index( PaO2 / FiO2) calculated daily | From inclusion to 30 days follow up | 
| Hospital Length of Stay | Hospital Length of stay | From inclusion to 30 days follow up | 
| Days on invasive mechanical ventilation | Days on mechanical ventilation for patients needing intubation & invasive mechanical ventilation | From inclusion to 30 days follow up | 
| Inflammatory Markers | Difference in the median levels of serum IL-6, serum ferritin, CRP at the end of the follow up period between all groups | From inclusion to 30 days | 
| Viral clearance | Rate of viral clearance as monitored by SARS-COV-2 PCR | From inclusion to 30 days | 
| Radiological assessment | Difference in the overall evaluation of pulmonary infiltrative (improving / deteriorating) as assessed by imaging (Chest X-ray or Non-contrast pulmonary CT) | From inclusion to 30 days | 
| Safety of Imatinib | Rate of serious adverse events (SAEs) | From inclusion to 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Pneumonia, ARDS, Cytokine Storm