Intravenous Imatinib in Mechanically Ventilated COVID-19 Patients

ABSTRACT

ConditionARDS;Acute Respiratory Distress Syndrome;Covid19;Endothelial Dysfunction;Pulmonary Edema

InterventionDrug Imatinib Mesylate intravenous solution;Drug Placebo

Primary outcome:Change in extravascular lung water index

Criteria
Inclusion Criteria

- Age = 18 years;

- Moderate-severe ARDS, as defined by Berlin definition for ARDS (onset within 1 week of
a known clinical insult or new or worsening respiratory symptoms, bilateral opacities
not fully explained by effusions, lobar/lung collapse, or nodules, respiratory failure
not fully explained by cardiac failure or fluid overload and P/F ratio =200 mmHg with
PEEP =5 cmH2O), and intubated for mechanical ventilation.

- PCR positive for SARS-CoV2 within the current disease episode.

- Provision of signed written informed consent from the patient or patient's legally
authorised representative;

Exclusion Criteria

- Persistent septic shock (>24h) 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;

- Pre-existing chronic pulmonary disease, including

- Known diagnosis of Interstitial Lung disease

- Known diagnosis of COPD GOLD Stage IV or FEV1<30% predicted

- DLCO <45% (if test results are available)

- Total lung capacity (TLC) < 60% of predicted (if test results are available);

- Chronic home oxygen treatment;

- Pre-existing heart failure with a known left ventricular ejection fraction <40%;

- Active treatment of haematological or non-haematological cancer with targeted immuno-
or chemotherapy, or thoracic radiotherapy in the last year;

- Currently receiving extracorporeal life support (ECLS);

- Severe chronic liver disease with Child-Pugh score > 12;

- Subjects in whom a decision to withdraw medical care is made (e.g. palliative
setting);

- Inability of the ICU staff to initiate IMP administration within 48 hours of
intubation;

- Known to be pregnant or breast-feeding;

- Enrolled in a concomitant clinical trial of an investigational medicinal product;

- White blood count < 2.5x109/l;

- Haemoglobin < 4.0 mmol/l;

- Thrombocytes < 50x109/l;

- The use of strong CYP3A4 inducers, including the following drugs

- Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum,
mitotaan, nevirapine, primidon, rifabutine, rifampicine;