Pharmacokinetics of Voriconazole in Adult ECMO Patients

Covid19 Clinical Trial

Official title:

An Observational 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04868188
• Other study ID #: 136965 V1.0
• Status: Recruiting
• Start date: August 24, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: University Hospitals, Leicester
• Contact: Hakeem Yusuff, MD
• Phone: 07789 880920
• Email: hakeem.yusuff[@]uhl-tr.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Given the high burden of fungal co-infection in patients admitted to ICU and improved outcomes with prompt anti-fungal treatment, it is of vital importance that the doses of anti-fungal are optimum to improve the dismal outcome of influenza/Covid-19 Associated Pulmonary Aspergillosis.

Due to the reported difficulties in dosing appropriately in ECMO patients, a prospective observational study is required to accurately evaluate the pharmacokinetics of voriconazole in patients supported on ECMO. This is to ensure that the dose of voriconazole is optimised to improve efficacy and reduce toxicity.

Description:

A single centre, open label, prospective, observational, pharmacokinetic study of voriconazole administered to adults (aged > 18 years) supported on ECMO. This is a low-interventional study. There will be no treatment changes as a result of participation in this study. The decision to initiate voriconazole therapy will be taken independent of this study protocol. Intravenous voriconazole will be prescribed according to the approved dose in the SmPC. All adults requiring voriconazole therapy will be eligible for recruitment into the study.

The only additional procedure in this study will be to take a total of 5 blood samples across 3 occasions/sampling windows (Day 1-4, Day 6-9 and Day 11-14) to determine plasma concentrations of voriconazole. In addition, a single buccal swab to determine the CYP2C19 genotype will be undertaken during the course of ICU stay.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults aged =18 years

2. Admitted to ICU on ECMO support

3. Positive influenza or SARS-CoV-2 PCR from nasal, throat swab, BAL or other respiratory specimen.

4. Positive invasive aspergillosis infection (positive Aspergillus species culture from respiratory specimen or positive serum galactomannan) or strong clinical suspicion of invasive aspergillosis infection based on symptoms, CT, CXR.

Exclusion Criteria:

1. No participants < 18 years of age

2. Not requiring ECMO support

3. No positive influenza or SARS-CoV-2 results

4. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Related Conditions & MeSH terms

• Aspergillosis
• COVID-19
• Covid19
• Influenza
• Influenza, Human

Intervention

Other:
• 5 blood samples
5 blood samples across 3 occasions/sampling windows (Day 1-4, Day 6-9 and Day 11-14) to determine plasma concentrations of voriconazole

Genetic:
• Determination of CYP2C19 genotype
A single buccal swab to determine the CYP2C19 genotype will be undertaken during the course of ICU stay.

Locations

Country	Name	City	State
United Kingdom	University Hospitals of Leicester	Leicester

Sponsors (1)

Lead Sponsor	Collaborator
University Hospitals, Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.	Primary parameter: Clearance (CL)	14 days
Primary	Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.	Primary parameter: Volume of distribution (V)	14 days
Primary	Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.	Secondary parameters: Maximum plasma concentration (Cmax)	14 days
Primary	Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.	Secondary parameters: Area under plasma concentration time curve (AUC)	14 days
Primary	Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.	Secondary parameters: Half-life (t1/2)	14 days
Secondary	To assess the influence of CYP2C19 genotype on the plasma levels of voriconazole	CYP2C19 genotype: identify *2, *3, and *17 mutations and any influence on plasma levels of voriconazole	14 days