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CounterCOVID

Projectomschrijving

Een op de vijf patiënten met COVID-19 krijgt ernstige longschade, waardoor opname in een ziekenhuis of zelfs op een Intensive Care noodzakelijk is. Deze longschade ontstaat onder meer door lekkage in de kleinste bloedvaatjes van de long, waarbij vocht uit de bloedbaan treedt en de longblaasjes opvult. Door het vocht in de longblaasjes wordt de zuurstofopname ernstig belemmerd en ontstaat levensbedreigend zuurstoftekort. Er zijn op dit moment geen medicijnen om lekkage van kleine bloedvaatjes tegen te gaan.

Onderzoek en verwachte uitkomsten

Eerder onderzoek in het laboratorium heeft laten zien dat het bestaande geneesmiddel imatinib lekkage van bloedvaatjes tegengaat. Dit beschermend effect van imatinib op de bloedvatwand kan daarom mogelijk worden ingezet bij patiënten met COVID-19.
In de COUNTER-COVID studie wordt getest of patiënten die behandeld worden met imatinib sneller herstellen dan patiënten die de standaard zorg krijgen.

Producten

Titel: Immunomodulation and endothelial barrier protection mediate the association between oral imatinib and mortality in hospitalised COVID-19 patients
Auteur: Justin de Brabander, Erik Duijvelaar, Job R. Schippers, Patrick J. Smeele, Hessel Peters-Sengers, Jan Willem Duitman, Jurjan Aman, Harm J. Bogaard, Tom van der Poll, Lieuwe D.J. Bos on behalf of the CounterCOVID study group
Magazine: European Respiratory Journal
Titel: Elevated acute phase proteins affect pharmacokinetics in COVID-19 trials: Lessons from the CounterCOVID - imatinib study
Auteur: Imke H. Bartelink,Pierre M. Bet,Nicolas Widmer,Monia Guidi,Erik Duijvelaar,Bram Grob,Richard Honeywell,Amanda Evelo,Ivo P. E. Tielbeek,Sue D. Snape,Henrike Hamer,Laurent A. Decosterd,Harm Jan Bogaard,Jurjan Aman,Eleonora L. Swart
Magazine: CPT: Pharmacometrics & Systems Pharmacology
Titel: Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial
Auteur: Jurjan Aman, PhD Erik Duijvelaar, MD Liza Botros, MD † Azar Kianzad, MD † Job R Schippers, MD † Patrick J Smeele, MD † Sara Azhang, MD Imke H Bartelink, PhD Ahmed A Bayoumy, MD Pierre M Bet, PhD Wim Boersma, PhD Peter I Bonta, PhD Karin A T Boomars, PhD Lieuwe D J Bos, PhD Job J M H van Bragt, PharmD Gert-Jan Braunstahl, PhD Lucas R Celant, MD Katrien A B Eger, MD J J Miranda Geelhoed, PhD Yurika L E van Glabbeek, MD Hans P Grotjohan, PhD Laura A Hagens, MSc Chris M Happe, PhD Boaz D Haz
Magazine: Lancet respiratory medicine
Titel: Cardiac safety of imatinib for the treatment of Covid-19: a secondary analysis of a randomised, double blind, placebo-controlled trial
Auteur: Duijvelaar, E. MD1,*; Vanhove, A.1,*; Schippers, J.R. MD1; Smeele, P.J. MD1; de Man, F.S. PhD1; Pinto, Y. PhD2; Aman, J. PhD1; Bogaard, H.J. PhD1; CounterCOVID Collaborative Group
Magazine: Journal of Cardiovascular Pharmacology
Titel: Long-term clinical outcomes of COVID-19 patients treated with imatinib
Auteur: Erik Duijvelaar Job R Schippers Patrick J Smeele Michiel Alexander de Raaf Arthur L E M Vanhove Siebe G Blok CounterCOVID Collaborative Group Jos W R Twisk Anton Vonk Noordegraaf Frances S de Man Harm Jan Bogaard Jurjan Aman
Magazine: Lancet respiratory medicine
Titel: Pharmacokinetics and pharmacodynamics of imatinib for optimal drug repurposing from cancer to COVID-19
Auteur: Nadia Baalbaki, Erik Duijvelaar, Medhat M Said, Job Schippers, Pierre M Bet, Jos Twisk, Sarah Fritchley, Cristina Longo, Kazien Mahmoud, Anke H Maitland-van der Zee, Harm Jan Bogaard, Eleonora L Swart, Jurjan Aman, Imke H Bartelink
Magazine: European Journal of Pharmaceutical Sciences

Verslagen


Samenvatting van de aanvraag

The COVID-19 pandemic has an unprecedented impact on global health, carrying a high burden for the individual patient and at society level. An important driver of this burden is hypoxemic respiratory failure (described as ‘severe’ COVID19), resulting from damage to the alveolocapillary barrier, excessive vascular leakage and pulmonary edema. Current management is supportive, and there is still no direct therapy available to treat severe Covid19. In the last decade we and other groups have shown that the clinically available Abl kinase inhibitor imatinib protects vascular integrity and can be used to treat vascular leak and pulmonary edema. Of note, imatinib was also shown to have antiviral properties, among others in SARS and MERS. Based on these properties we hypothesize that imatinib can reduce disease burden and health resource consumption in patients with severe Covid19. To test this hypothesis we initiated a randomized, placebo-controlled clinical trial to test a 10-day course of oral imatinib in patients with severe Covid19, aiming to reduce the need for oxygen and ventilatory support. This trial has obtained IRB approval and has thus far included >80patients in 10 centers in the Netherlands, thereby being one of the largest investigator-driven Covid19 intervention studies in the Netherlands. With the current proposal we aim to further increase the network of participating centers to 20 centers, to sustain the inclusion rate and finish the trial end 2020. As national referral center for pulmonary vascular disease, we will use an established large network of referring non-academic hospitals to realize this. If proven effective in this trial, it can be integrated swiftly in Covid19 management, also in low-income countries given the fact that oral imatinib is generically available. Future perspectives include application of imatinib beyond Covid19, for other diseases characterized by pulmonary vascular leak.

Onderwerpen

Kenmerken

Projectnummer:
10430012010007
Looptijd: 100%
Looptijd: 100 %
2020
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
prof. dr. H.J. Bogaard
Verantwoordelijke organisatie:
Amsterdam UMC Locatie VUmc