COVID-19 related Acute Respiratory Distress Syndrome (ARDS) in mechanically-ventilated patients on the Intensive Care Unit. MedDRA version: 23.0 Level: LLT Classification code 10084270 Term: SARS-CoV-2 acute respiratory disease System Organ Class: 100000004862
Conditions
Interventions
Product Name: Imatinib (8 mg/mL) solution for infusion
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: IMATINIB MESILATE
CAS Number: 220127-57-1
Other descriptive name: Imatinib mesila
imatinib mesylate
imatinib methanesulfonate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 8-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: I
Sponsors
Amsterdam Universitair Medische Centra, location VUmc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years; 2. Moderate-severe ARDS, as defined by Berlin definition for ARDS, and intubated for mechanical ventilation. 3. PCR positive for SARS-CoV2 within the current disease episode. 4. Provision of signed written informed consent from the patient or patient's legally authorised representative; Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. 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; 2. Pre-existing chronic pulmonary disease, including: o Known diagnosis of Interstitial Lung disease o Known diagnosis of COPD Gold IV or FEV1 12; 8. Subjects in whom a decision to withdraw medical care is made (e.g. palliative setting); 9. Inability of the ICU staff to initiate study drug administration within 48 hours of screening; 10. Known to be pregnant or breast-feeding; 11. Enrolled in a concomitant clinical trial of an investigational medicinal product; 12. White blood count < 2.5x109/l; 13. Haemoglobin < 4.0 mmol/l; 14. Thrombocytes < 50x109/l; 15. The use of strong CYP3A4 inducers, including the following drugs: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and effectiveness of imatinib mesilate solution for direct intravenous (iv) injection in mechanically-ventilated subjects with COVID-19-related ARDS. ;Secondary Objective: Not applicable.;Primary end point(s): The primary endpoint is the change in extravascular lung water index (?EVLWi) between Day 1 (baseline) and Day 4, as measured by PICCO catheter.;Timepoint(s) of evaluation of this end point: Day 1 (baseline), day 2, day 4 and day 7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pulmonary edema, gas-exchange and respiratory mechanics: • Extravascular Lung Water Index (Day 1, 2, 4 and 7) • Pulmonary vascular permeability index (Day 1, 2, 4 and 7) • Oxygenation index (Day 1, 2, 4, 7, 10 and Day 28, if available) • PaO2/FiO2 ratio (Day 1, 2, 4, 7, 10 and Day 28, if available) • Airway driving pressure (Day 1, 2, 4, 7, 10 and on Day 28, if available) • Compliance of the respiratory system (Day 1, 2, 4, 7, 10 and on Day 28, if available) • Mechanical power (Day 1,2,4,7,10 and on Day 28 if available) Inflammation, endothelial injury and lung epithelial injury: • Plasma biomarkers of inflammation, endothelial injury and lung epithelial injury (Day 1, 2, 4, 7 and 10) Organ function and outcome: • Sequential Organ Failure Assessment (SOFA) score (Day 1, 2, 4, 7, 10 and on Day 28, if available) • Number of ventilator-free days and alive at day 28 • Duration of mechanical ventilation (days) till day 28 • Length of ICU stay (days) till day 28 • Hospital length of stay (days) till day 28 • 28-day mortality Safety parameters o Blood cell count, i.e. haemoglobin, thrombocytes and leucocytes (Day 1,2,4,7 and 10) o Kidney function, estimated glomerular filtration rate, sodium and potassium (Day 1,2,4,7 and 10) o Liver enzymes, i.e. ASAT, ALAT, Alkaline Phosphatase, ?- glutamyltransferase, bilirubin (Day 1,2,4,7 and 10) o NT-proBNP (Day 1,2,4,7 and 10) o SAEs / AE o Corrected QT interval at ECG (Day 1,2,4,7 and 10) Pharmacokinetics o Study drug plasma levels at 4h and 8h after administration (Day 1) and on Day 2,4,7,10 o In a subpopulation study drug plasma levels during administration and 2h after administration. o Albumin, AGP1 at 4h, 8h, Day 2,4,7 and 10.;Timepoint(s) of evaluation of this end point: - Extravascular Lung Water and pulmonary vascular permeability Index: Day 1, 2, 4 and 7. - Other parameters of gas-exchange and respiratory mechanics: Day 1, 2, 4, 7, 10 and Day 28 - Plasma biomarkers of inflammation, endothelial in | — |
Countries
Netherlands
Contacts
Public ContactDr. Jurjan Aman
Amsterdam Universitair Medische Centra, location VUmc
Outcome results
None listed