Pharmacokinetics of Voriconazole in adult ECMO patients
Research type
Research Study
Full title
An single centre, prospective, pharmacokinetic study of intravenous voriconazole used for treatment of invasive aspergillosis in adult patients with severe influenza / COVID-19 supported with extra-corporeal membrane oxygenation (ECMO)
IRAS ID
291410
Contact name
Hakeem Yusuff
Contact email
Sponsor organisation
University Hospitals of Leicester
Eudract number
2020-005921-99
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 5 months, 31 days
Research summary
Extracorporeal membrane oxygenation (ECMO) is a life support system for the heart and lungs of critically ill patients. The ECMO machine is similar to the heart-lung by-pass machine used in open-heart surgery. It pumps and oxygenates a patient’s blood outside the body, allowing the heart and lungs to rest.\nVoriconazole is an antifungal drug and has shown to be highly effective at treating fungal infections at recommended doses in normal ICU patients. However, dosing information in patients requiring ECMO support is lacking. This may be important as it is known that ECMO circuits alter how drugs are handled by the body. The purpose of this study is to determine whether we are getting the dose of voriconazole right for adult patients on ECMO support.\nThis is a pharmacokinetic study of intravenous voriconazole administered to adults (> 18 years) receiving ECMO support in the ICU at Glenfield Hospital, Leicester. Based on historical data, an estimated 30 patients are expected to be recruited over the study period. \nPatients recruited to the study will receive intravenous voriconazole as part of their clinical management plan. The decision to administer or commence on IV voriconazole will be based solely on clinical assessment of the patient by the responsible clinical team and will not be influenced in any way by the research or members of the research team. The study does not require randomisation or blinding.\nPatients will be administered twice daily doses of voriconazole for the duration of therapy, typically for a maximum of 14-28 days (the typical duration of anti-fungal treatment on ECMO). The duration of study for each patient will be therefore up to 28 days and the study will last for 18 months.\nCurrently in routine clinical care, voriconazole is monitored during treatment by taking a single blood sample to check the concentration. This is usually done on one occasion after at least 3-4 doses have been administered. In this study, 5 blood samples will be taken across 3 dosing occasions to determine concentrations of voriconazole and to build a pharmacokinetic model. In addition, a genetic test for the enzyme CYP2C19 will be done by taking a cheek swab. This enzyme is responsible for breaking down voriconazole in the body. The genetic test will determine if different genotypes of this enzyme affects the concentration of voriconazole in blood.\n
REC name
South Central - Oxford B Research Ethics Committee
REC reference
21/SC/0076
Date of REC Opinion
6 May 2021
REC opinion
Further Information Favourable Opinion