Countering Lung Damage in COVID-19 infection: the CounterCovid Study

Conditions

Covid19 is characterized by hypoxemic respiratory failure, caused by extensive vascular leak and pulmonary edema early in the course of disease.

Duijvelaar E, Gisby J, Peters JE, Bogaard HJ, Aman J.

2024-01-2515 citations

10.1038/s41467-024-44986-w

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial.

Aman J, Duijvelaar E, Botros L, Kianzad A, Schippers JR, Smeele PJ, Azhang S, Bartelink IH, Bayoumy AA, Bet PM, Boersma W, Bonta PI, Boomars KAT, Bos LDJ, van Bragt JJMH, Braunstahl GJ, Celant LR, Eger KAB, Geelhoed JJM, van Glabbeek YLE, Grotjohan HP, Hagens LA, Happe CM, Hazes BD, Heunks LMA, van den Heuvel M, Hoefsloot W, Hoek RJA, Hoekstra R, Hofstee HMA, Juffermans NP, Kemper EM, Kos R, Kunst PWA, Lammers A, van der Lee I, van der Lee EL, Maitland-van der Zee AH, Mau Asam PFM, Mieras A, Muller M, Neefjes ECW, Nossent EJ, Oswald LMA, Overbeek MJ, Pamplona CC, Paternotte N, Pronk N, de Raaf MA, van Raaij BFM, Reijrink M, Schultz MJ, Serpa Neto A, Slob EMA, Smeenk FWJM, Smit MR, Smits AJ, Stalenhoef JE, Tuinman PR, Vanhove ALEM, Wessels JN, van Wezenbeek JCC, Vonk Noordegraaf A, de Man FS, Bogaard HJ.

2021-06-1887 citations

10.1016/s2213-2600(21)00237-x

Interventions

Trade Name: Imatinib mesilate Product Name: Imatinib mesilate Product Code: L01XE01 Pharmaceutical Form: Tablet Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Age >18 years - Hospital admission with proven SARS2-Covid19 infection - Hypoxemic respiratory failure (SaO2 =65 years) yes F.1.3.1 Number of subjects for this age range 186

Exclusion criteria

Exclusion criteria: - Pre-existing chronic pulmonary disease - Former diagnosis of Interstitial pulmonary disease - Former diagnosis of COPD 4 or FEV15 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN - History or suspicion of inability to cooperate adequately. - White blood count 500msec at baseline.

Design outcomes

Primary

Measure	Time frame
Main Objective: To test whether treatment with oral imatinib reduce disease burden and consumption of medical resources.;Secondary Objective: Secondary objectives are to evaluate the pharmacokinetics and immunomodulatory actions of a 10-day course of oral imatinib in patients with severe COVID-19 disease.;Primary end point(s): Time to liberation from ventilation and supplemental oxygen >48h while being alive during a 28-day period after randomization;Timepoint(s) of evaluation of this end point: 28 days	—

Measure

Time frame

Main Objective: To test whether treatment with oral imatinib reduce disease burden and consumption of medical resources.;Secondary Objective: Secondary objectives are to evaluate the pharmacokinetics and immunomodulatory actions of a 10-day course of oral imatinib in patients with severe COVID-19 disease.;Primary end point(s): Time to liberation from ventilation and supplemental oxygen >48h while being alive during a 28-day period after randomization;Timepoint(s) of evaluation of this end point: 28 days

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Secondary

Measure	Time frame
Secondary end point(s): - Secondary efficacy parameters o 28-day mortality o Need for ICU admission o Length of ICU admission o Need for invasive ventilation o Length of invasive ventilation o Days on ventilator o Need for ECMO o Need for non-invasive ventilation o Length of non-invasive ventilation o SpO2 at Day 1,2,3,4,5,7,9 o Fi O2 at Day 1,2,3,4,5,7,9 o SpO2/FiO2 at Day 1,2,3,4,5,7,9 - Safety parameters o Blood cell count Day 0,1,2,3,5,7,9 o Kidney function Day 0,1,2,3,5,7,9 o Liver enzymes Day 0,1,2,3,5,7,9 o NTproBNP at Day 0,1,2,3,5,7,9 o SAEs / AE o ECG at Day 1,3,5,9 - Pharmacokinetics o Study drug plasma levels at 4h, 8h, Day 1,3,5,7,9 o Albumin, AGP1 at Day 0,1,2,3,5,7,9 - Immune responses (subgroups of 50 patients per study arm) o Host response plasma biomarkers on day 0, 5 and 9, and on the first day of any additional interventions (invasive ventilation, CT scanning, bronchoscopy). o Neutrophil RNA sequencing, metabolomics and lipidomics on day 0 and 5 o Phenotypic and functional analysis of whole blood, peripheral blood mononuclear cells and polymorphonuclear leukocytes on day 0 and 5, and on the first day of additional interventions (invasive ventilation, CT scanning, bronchoscopy). - Fibrotic responses (subgroups of 50 patients per study arm) o Fibrotic plasma biomarkers on day 0, 5 and 9, and on the first day of any additional interventions (invasive ventilation, CT scanning, bronchoscopy) ;Timepoint(s) of evaluation of this end point: 28 days	—

Measure

Time frame

Secondary end point(s): - Secondary efficacy parameters o 28-day mortality o Need for ICU admission o Length of ICU admission o Need for invasive ventilation o Length of invasive ventilation o Days on ventilator o Need for ECMO o Need for non-invasive ventilation o Length of non-invasive ventilation o SpO2 at Day 1,2,3,4,5,7,9 o Fi O2 at Day 1,2,3,4,5,7,9 o SpO2/FiO2 at Day 1,2,3,4,5,7,9 - Safety parameters o Blood cell count Day 0,1,2,3,5,7,9 o Kidney function Day 0,1,2,3,5,7,9 o Liver enzymes Day 0,1,2,3,5,7,9 o NTproBNP at Day 0,1,2,3,5,7,9 o SAEs / AE o ECG at Day 1,3,5,9 - Pharmacokinetics o Study drug plasma levels at 4h, 8h, Day 1,3,5,7,9 o Albumin, AGP1 at Day 0,1,2,3,5,7,9 - Immune responses (subgroups of 50 patients per study arm) o Host response plasma biomarkers on day 0, 5 and 9, and on the first day of any additional interventions (invasive ventilation, CT scanning, bronchoscopy). o Neutrophil RNA sequencing, metabolomics and lipidomics on day 0 and 5 o Phenotypic and functional analysis of whole blood, peripheral blood mononuclear cells and polymorphonuclear leukocytes on day 0 and 5, and on the first day of additional interventions (invasive ventilation, CT scanning, bronchoscopy). - Fibrotic responses (subgroups of 50 patients per study arm) o Fibrotic plasma biomarkers on day 0, 5 and 9, and on the first day of any additional interventions (invasive ventilation, CT scanning, bronchoscopy) ;Timepoint(s) of evaluation of this end point: 28 days

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Countries

Belgium, Netherlands

Contacts

Public ContactJurjan Aman

Amsterdam UMC

j.aman@amsterdamumc.nl+31610738910

Outcome results

None listed