Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial

• Published in: Current controlled trials in cardiovascular medicine 2020-10, Vol.21 (1), p.897-5, Article 897
• Main Authors: Emadi, Ashkan, Chua, Joel V, Talwani, Rohit, Bentzen, Søren M, Baddley, John
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Angina pectoris; Betacoronavirus - drug effects; Betacoronavirus - isolation & purification; Cellulose; Clinical trials; Coronavirus Infections - diagnosis; Coronavirus Infections - drug therapy; Coronaviruses; COVID-19; Critical Care - methods; Dose-Response Relationship, Drug; Double-Blind Method; Drug Monitoring; Drug stores; Drug therapy; Extracorporeal membrane oxygenation; Female; Hospital patients; Hospitalization; Humans; Hypotheses; Illnesses; imatinib; Imatinib mesylate; Imatinib Mesylate - administration & dosage; Imatinib Mesylate - adverse effects; Informed consent; Intensive care; Letter; Male; Mortality; Pandemics; Patients; Pneumonia, Viral - diagnosis; Pneumonia, Viral - drug therapy; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; protocol; Randomised controlled trial; Randomized Controlled Trials as Topic; Renal replacement therapy; SARS-CoV; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Testing; Treatment Outcome; tyrosine kinase inhibitor; Ventilators; Women
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-020-04819-9

Primary Objective: To evaluate the efficacy and safety of oral administration of imatinib combined with the Best Conventional Care (BCC) versus placebo plus BCC in hospitalized patients with COVID-19. Addition of imatinib to the BCC will provide a superior clinical outcome for patients with COVID-19 compared with BCC plus placebo. This hypothesis is on the basis of 1) intralysosomal entrapment of imatinib will increase endosomal pH and effectively decrease SARS-CoV-2/cell fusion, 2) kinase inhibitory activity of imatinib will interfere with budding/release or replication of SARS-CoV-2, and 3) because of the critical role of mechanical ventilation in the care of patients with ARDS, imatinib will have a significant clinical impact for patients with critical COVID-19 infection in Intensive Care Unit (ICU). This is an individual patient-level randomized, double-blind, placebo-controlled, two-parallel arm phase 3 study to evaluate the safety and efficacy of imatinib for the treatment of hospitalized adults with COVID-19. Participants will be followed for up to 60 days from the start of study drug administration. This trial will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. Inclusion Criteria: Patients may be included in the study only if they meet all of the following criteria: 1) Ability to understand and willingness to sign a written informed consent document. Informed consent must be obtained prior to participation in the study. For patients who are too unwell to provide consent such as patients on invasive ventilator or extracorporeal membrane oxygenation (ECMO), their Legally Authorized Representative (LAR) can sign the informed consent, 2) Hospitalized patients ≥18 years of age, 3) Positive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 in the respiratory tract sample (oropharyngeal, nasopharyngeal or bronchoalveolar lavage (BAL)) by Center for Disease Control or local laboratory within 7 days of randomization, 4) Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study. Patients meeting any of the following criteria are not eligible for the study: 1) Patients receiving any other investigational agents in a clinical trial. Off-label use of agents such as hydroxychloroquine is not an exclusion criterion, 2) Pregnant or breastfeeding women,