Pharmacokinetics of Voriconazole in Adult ECMO Patients

NCT04868188 | Completed

• 1 other identifier: 136965 V1.0
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aspergillosis; Influenza; Covid19

Keywords

Voriconazole; Extracorporeal Membrane Oxygenation

Outcome Measures

Primary Outcomes (5)

• Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.

  Primary parameter: Clearance (CL)

  14 days

• 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

• 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

• 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

• 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 Outcomes (1)

• To assess the influence of CYP2C19 genotype on the plasma levels of voriconazole

  14 days

Study Arms (1)

Voriconazole administration to adult patients with suspected fungal disease, receiving ECMO support

Adult (\>18 years) patients with severe influenza / Covid-19 supported on ECMO and with confirmed or suspected aspergillosis infection.

Other: 5 blood samples; Genetic: Determination of CYP2C19 genotype

Interventions

5 blood samples OTHER

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

Voriconazole administration to adult patients with suspected fungal disease, receiving ECMO support

Determination of CYP2C19 genotype GENETIC

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

Voriconazole administration to adult patients with suspected fungal disease, receiving ECMO support

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients (≥18 years) with acute (cardio-)respiratory failure, inadequately supported by mechanical ventilation, requiring additional support with ECMO, and in the opinion of the direct care team requires intravenous voriconazole therapy for treatment of confirmed or suspected invasive aspergillosis, will be eligible to be recruited.

You may qualify if:

• Adults aged ≥18 years
• Admitted to ICU on ECMO support
• Positive influenza or SARS-CoV-2 PCR from nasal, throat swab, BAL or other respiratory specimen.
• 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.

You may not qualify if:

• No participants \< 18 years of age
• Not requiring ECMO support
• No positive influenza or SARS-CoV-2 results
• 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.

Sponsors & Collaborators

• University Hospitals, Leicester: lead

Study Sites (1)

University Hospitals of Leicester

Leicester, United Kingdom

Location

MeSH Terms

Conditions

Aspergillosis; Influenza, Human; COVID-19

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Lung Diseases

Study Officials

• Hakeem Yusuff, MD

  University Hospitals, Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: April 30, 2021
• Study Start: August 10, 2021
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)