AspergillosisNCT04868188
Pharmacokinetics of Voriconazole in Adult ECMO Patients
An observational study of Aspergillosis and Influenza, run by University Hospitals, Leicester at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aspergillosis, Influenza, Covid19
- What is being tested?
- 5 blood samples and Determination of CYP2C19 genotype
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Aug 2021to 31 May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the detailed 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.
- Conditions
- Aspergillosis, Influenza, Covid19
- Being tested
- 5 blood samples, Determination of CYP2C19 genotype
- Keywords
- Voriconazole, Extracorporeal Membrane Oxygenation
- Medical subject headings
- Aspergillosis, Influenza, Human, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5 blood samplesOther
5 blood samples across 3 occasions/sampling windows (Day 1-4, Day 6-9 and Day 11-14) to determine plasma concentrations of voriconazole
Determination of CYP2C19 genotypeGenetic
A single buccal swab to determine the CYP2C19 genotype will be undertaken during the course of ICU stay.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: 5 blood samples; Genetic: Determination of CYP2C19 genotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.
Primary parameter: Clearance (CL)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 14 days
Secondary outcomes (1)
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
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2021
- Study start10 Aug 2021
- Primary completion31 May 2025
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AspergillosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals, Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hakeem Yusuff, MD, Principal investigator, University Hospitals, Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04868188
- Sponsor's protocol ID
- 136965 V1.0
- Status last verified
- Dec 2025
- First submitted
- 18 Feb 2021
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yusuff H, Gadsby J, Isgro G, Zochios V, Jenkins D, Cooke S, Mulla H. Time-varying voriconazole clearance during extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 2026 Jun 3;70(6):e0009826. doi: 10.1128/aac.00098-26. Epub 2026 Apr 30.
PubMed 42059809
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04868188
- Acronym / sponsor ID
- 136965 V1.0
- Conditions
- Aspergillosis, Influenza, Covid19
- Keywords
- Voriconazole, Extracorporeal Membrane Oxygenation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University Hospitals, LeicesterUniversity, hospital or other
- Study start
- 10 Aug 2021 (actual)
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 30 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Voriconazole administration to adult patients with suspected fungal disease, receiving ECMO support | – | Other: 5 blood samples, Genetic: Determination of CYP2C19 genotypeAdult (>18 years) patients with severe influenza / Covid-19 supported on ECMO and with confirmed or suspected aspergillosis infection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5 blood samples5 blood samples across 3 occasions/sampling windows (Day 1-4, Day 6-9 and Day 11-14) to determine plasma concentrations of voriconazole | Other | Voriconazole administration to adult patients with suspected fungal disease, receiving ECMO support |
| Determination of CYP2C19 genotypeA single buccal swab to determine the CYP2C19 genotype will be undertaken during the course of ICU stay. | Genetic | Voriconazole administration to adult patients with suspected fungal disease, receiving ECMO support |
Primary outcome
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.
Time frame: 14 days
Primary parameter: Clearance (CL)
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.
Time frame: 14 days
Primary parameter: Volume of distribution (V)
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.
Time frame: 14 days
Secondary parameters: Maximum plasma concentration (Cmax)
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.
Time frame: 14 days
Secondary parameters: Area under plasma concentration time curve (AUC)
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support.
Time frame: 14 days
Secondary parameters: Half-life (t1/2)
1 secondary outcome
To assess the influence of CYP2C19 genotype on the plasma levels of voriconazole
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
- Derived from this study: PubMed 42059809Yusuff H, Gadsby J, Isgro G, Zochios V, Jenkins D, Cooke S, Mulla H. Time-varying voriconazole clearance during extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 2026 Jun 3;70(6):e0009826. doi: 10.1128/aac.00098-26. Epub 2026 Apr 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hakeem Yusuff, MD principal investigator
University Hospitals, Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aspergillosis and Influenza, run by University Hospitals, Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma levels of voriconazole administered to critically ill adult patients with suspected fungal disease, receiving ECMO support. (time frame: 14 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04868188, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.