No registrations found.
ID
Source
Brief title
Health condition
Covid19 positive pneumonitis with need for hospital admission
Sponsors and support
Intervention
Outcome measures
Primary outcome
time to liberation from ventilation and supplemental oxygen and alive during a 28day period after randomization
Secondary outcome
o 28-day mortality
o Need for ICU admission
o Length of ICU admission
o Need for invasive ventilation
o Days on ventilator
o Need for ECMO
o Need for non-invasive ventilation
o SpO2 at Day 1,2,3,4,5,8,10
o Fi O2 at Day 1,2,3,4,5,8,10
o SpO2/FiO2 at Day 1,2,3,4,5,8,10
o Viral clearance at Day 5 and 10.
o Blood cell count Day 0,1,2,3,5,7,10
o Kidney function Day 0,1,2,3,5,7,10
o Liver enzymes Day 0,1,2,3,5,7,10
o NTproBNP at Day 0,1,2,3,5,7,10
o SAEs / AE
o ECG at Day 1,3,5,10
o Study drug plasma levels at 4h, 8h, Day 1,3,5,7,10
o Albumin, AGP1 at Day 0,1,2,3,5,7,10
Background summary
Rationale: Covid19 infection is characterized by hypoxemic respiratory failure, caused by extensive vascular leak and pulmonary edema early in the course of disease. Although there is no proven therapy to reduce viral replication in Covid19, recent studies from our department have discovered that the tyrosine kinase inhibitor imatinib reinforces the endothelial barrier and prevents vascular leak in inflammatory conditions, while leaving the immune response intact. We hypothesize that reversing vascular leak is an effective approach to reduce disease burden and consumption of medical resources.
Objective: To test whether treatment with oral imatinib reduce disease burden and consumption of medical resources.
Study design: A randomized, double-blind, placebo controlled, clinical trial.
Study population: Patients (>18years) with proven Covid19 infection, admitted to the hospital with hypoxemic respiratory failure (SaO2<92% or kPa<8 on room air), with a study population of 386 patients (193/arm).
Intervention (if applicable): The intervention group will receive a starting dose of 800mg oral imatinib, followed by 400mg od during 10 days. The control group will receive a similar dosing schedule with a placebo.
Main study parameters/endpoints: The main study parameter is the time to liberation from ventilation and supplemental oxygen and alive during a 28day period after randomization.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation involves randomization to either the intervention or the placebo group. In both groups patients will undergo blood sampling at 9 time-points, at each time-point 1 or 4 tubes of 5mL will be drawn. Additional tests include a viral swab from the throat at 2 time-points, and an ECG at 5 time-points. Part of these interventions are part of routine care. Physical discomfort associated with participation involves swallowing of tablets, and side effects of the study medication, which are considered mild (predominantly gastro-intestinal discomfort). Anticipated benefits from the study medication involve faster recovery from Covid19 and a lower risk for ICU admission or death.
Study objective
Our hypothesis is that treatment with imatinib results in a reduction of the time to liberation from ventilation and supplemental oxygen and alive in Covid19.
Study design
2
Intervention
Imatinib or placebo
Inclusion criteria
- Age >18 years
- Hospital admission with proven SARS2-Covid19 infection
- Hypoxemic respiratory failure (SaO2 <92%, PaO2 <8kPa)
- Ability to give informed consent
Exclusion criteria
1. Pre-existing chronic pulmonary disease, including:
Known diagnosis of Interstitial Lung disease
Former diagnosis of COPD 4 or FEV1<30%pred
DLCO <45%
Total lung capacity (TLC) < 60% of predicted
Lung cancer with non-surgical treatment in last year
2. Home oxygen treatment
3. Pre-existing heart failure with a known left ventricular ejection fraction <40%
4. Active treatment of hematological or non-hematological cancer with targeted, immuno- or chemotherapy in the last year
4. Inability to provide informed consent
5. Any subject who had received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study
6. Active liver disease, porphyria or elevations of serums transaminases >3 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN
7. History or suspicion of inability to cooperate adequately.
8. White blood count < 4.0^109/l
9. Hemoglobin < 6.0 mmol/l
10. Thrombocytes < 100^109/l
11. Pregnant female subjects
12. Breastfeeding female subjects
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8491 |
| Other | METC VUMC : 2020.158 |