Aspergillosis; Pulmonary, Invasive (Etiology)Phase 4POSA-FLUNCT03378479
Posaconazole for the Prevention of Influenza-associated Aspergillosis in Critically Ill Patients
A Phase 4 study testing SOC +Posaconazole 18 MG/ML (milligram/milliliter) in people with Aspergillosis; Pulmonary, Invasive (Etiology), run by Universitaire Ziekenhuizen KU Leuven at 12 sites in 3 countries.
Trial summary
The objective of this study is to deliver proof of concept that antifungal prophylaxis can reduce the incidence of Influenza Associated Aspergillosis (IAA) in ICU (intensive care unit) patients with severe influenza. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aspergillosis; Pulmonary, Invasive (Etiology)
- What is being tested?
- SOC +Posaconazole 18 MG/ML (milligram/milliliter)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 27 Dec 2017to 30 Mar 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Written informed consent must be obtained from the patient or his/her legal representative prior to any study procedures
- Adult patient (≥ 18 years)
- PCR-confirmed influenza based on nasopharyngeal swab (NS), bronchial aspirate (BA) or broncho-alveolar lavage (BAL) within 7 days before ICU admission or within 48 hours after ICU admission. If PCR is not available a positive result of a rapid test is required (a negative rapid test does not imply absence of influenza and thus requires confirmation by PCR)
- Influenza symptoms present for no more than 10 days before ICU admission
- Respiratory distress as the main reason for ICU admission. Respiratory distress will be defined as tachypnea with an respiratory rate ≥ 25x/min and a paO2/fiO2-ratio (fraction of inspired oxygen) ≤ 300 with or without (bilateral) infiltrates.
Who cannot join
- Patients with age < 18 years
- Pregnant women (based on a positive serum sample)
- Expected survival on ICU admission ≤ 48h
- Patients having influenza symptoms for more than 10 days before ICU admission
- Patients being transferred from another hospital ward or another hospital who already have mycological evidence for an IAA-infection (based on sputum, BA or BAL culture, BAL or serum GM)
- Patients with known intolerance or hypersensitivity to posaconazole or other azole antifungal agents
Show all 10Show fewer
- Patients that are being treated actively with antifungal agents for invasive aspergillosis
- Patients with a QTc (corrected QT interval) interval ≥500 msec
- Patients with liver cirrhosis (Child C)
- Participation in another interventional clinical trial -
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Netherlands5 sites
UMC Maastricht
Maastricht, 6229
UMC Radboud
Nijmegen, 6500
Canisius Wilhelmina Hospital
Nijmegen, 6532
MC Erasmus
Rotterdam, 3015
Elisabeth-TweeSteden Hospital
Tilburg, 5042
Belgium4 sites
AZ Sint Jan
Bruges, 8000
UZ Gent
Ghent, 9000
UZ Leuven
Leuven, 3000
AZ Delta
Roeselare, 8800
France3 sites
CHU Lille
Lille, 59000
Hospital Lariboisière
Paris, 75010
Hospital Saint-Louis
Paris, 75010
About this study
Official title: A Phase iv, Interventional, Non-blinded, Randomized Controlled Multicenter Study of Posaconazole Prophylaxis for the Prevention of Influenza-associated Aspergillosis (IAA) in Critically Ill Patients
The objective of this study is to deliver proof of concept that antifungal prophylaxis can reduce the incidence of Influenza Associated Aspergillosis (IAA) in ICU (intensive care unit) patients with severe influenza.
The investigators will perform an interventional non-blinded randomized controlled multicentric proof-of-concept study in patients with severe influenza admitted to the ICU. Patients will be randomized to the posaconazole prophylaxis group or to the SOC (standard of care) group. Oseltamivir will be started at the discretion of the investigator. Patients in the posaconazole group will receive posaconazole prophylaxis for 7 days.
addendum: pharmacokinetics of posaconazole as prophylaxis for invasive fungal disease on ICU
Read the detailed description
Critically ill patients with PCR-confirmed influenza criteria) are eligible for inclusion in this study and will be randomized to or the posaconazole prophylaxis group or the SOC group.
If a patient is randomized to the posaconazole prophylaxis group, posaconazole (Noxafil, MSD) will be started intravenously from day 1 of randomization (2*300mg( milligram) /d on day 1, followed by 1*300mg/d from day 2 for 7 days) In both patient groups (prophylaxis and SOC) oseltamivir (non-IMP) will be started at the discretion of the treating physician from the first day of ICU admission as 2*150 mg/day for 10 days. If oseltamivir had already been started up before ICU admission, oseltamivir treatment will be continued up to a total of 10 days.
Within 48 hours after influenza diagnosis a bronchoscopy with BAL (bronchoalveolar lavage) and a serum galactomannan will be performed as part of routine ICU care in this type of patients. If an IAA-infection is suspected based on the result of this BAL ((A) Aspergillus cultured from BAL, or (B) a galactomannan (GM)the patient will be withdrawn from the study and antifungal treatment will be started.
addendum: Extensive PK sampling (UZ Leuven and Radboud): full PK curve on day 2 and day 5 (predose, 1.5; 2,3,4,6,8,10,12,18,24 h post infusion).
on non PK days, until day 7, predose sample. PK in BAL fluid only in patients with mechanical ventilation and when medically indicated.
Limited PK sampling: on day 2 and day 5: 1.5-3h, 4-8 h;8-12h; 12-24h post dose. on non PK days: PK pre dose.
- Being tested
- SOC +Posaconazole 18 MG/ML (milligram/milliliter), standard of care (SOC)
- Keywords
- Influenza
- Medical subject headings
- Aspergillosis, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SOC +Posaconazole 18 MG/ML (milligram/milliliter)Drug
Also called Noxafil
.2*300mg/d IV on day 1, followed by 1*300mg/d IV from day 2 for 7 days (total 7 days)
standard of care (SOC)Other
treatment for influenza pneumonia at the investigators discretion
| Study group | Role | What they receive |
|---|---|---|
| SOC + 'Posaconazole 18 MG/ML' | Other | standard of care (SOC) treatment for influenza pneumonia +posaconazole 2*300mg/d IV on day 1, followed by 1*300mg/d IV from day 2 for 7 days; vials containing 18mg posaconazole /mL, 300mg posaconazole/vial in total) Receives: Drug: SOC +Posaconazole 18 MG/ML (milligram/milliliter); Other: standard of care (SOC) |
| Standard of Care | Other | standard of care treatment for influenza pneumonia (at the investigators discretion) Receives: Other: standard of care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With IAA-infection at ICU Discharge
A patient with IAA-infection is defined as a patient having mycological evidence of Aspergillus and at least one Aspergillus compatible sign or symptom and radiological abnormalities
Measured: from date of admission in ICU assessed up to ICU discharge, approximately 21 days
Secondary outcomes (6)
Time to IAPA Diagnosis
Days to influenza-associated pulmonary aspergillosis (IAPA) diagnosis
Measured: from date of inclusion to date of first sign/symptom of IAA infection, assessed up to ICU discharge, approximately 10 days
Length of ICU Stay
amount of days at ICU
Measured: from date of admission in ICU to date of discharge from ICU, approximately 20 days
Length of Hospital Stay
Number of days in the hospital
Measured: from date of admission in hospital to date of discharge from hospital, approximately 25 days
ICU Mortality - Number of Participant Deaths
survival status
Measured: At ICU discharge
Hospital Mortality - Number of Participant Deaths
Survival status at hospital discharge
Measured: At hospital discharge
90-day Mortality - Number of Participant Deaths
Survival status at 90 days after ICU admission
Measured: At 90 days after ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2017
- Study start27 Dec 2017
- Primary completion31 Mar 2020
- Study completion30 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aspergillosis; Pulmonary, Invasive (Etiology)Studies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Joost Wauters, prof. dr., Universitaire Ziekenhuizen KU Leuven
- Investigators
- Joost Wauters, Phd, Principal investigator, UZ LeuvenPaul Verweij, Phd, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03378479
- Sponsor's protocol ID
- POSA-FLU
- Acronym
- POSA-FLU
- Status last verified
- Mar 2025
- First submitted
- 30 Oct 2017
- Last updated
- 8 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Elkayal O, Mertens B, Wauters J, Debaveye Y, Rijnders B, Verweij PE, Bruggemann RJ, Spriet I, Dreesen E. Dosing of IV posaconazole to treat critically ill patients with invasive pulmonary aspergillosis: a population pharmacokinetics modelling and simulation study. J Antimicrob Chemother. 2024 Jul 1;79(7):1645-1656. doi: 10.1093/jac/dkae160.
PubMed 38828958Vanderbeke L, Janssen NAF, Bergmans DCJJ, Bourgeois M, Buil JB, Debaveye Y, Depuydt P, Feys S, Hermans G, Hoiting O, van der Hoven B, Jacobs C, Lagrou K, Lemiale V, Lormans P, Maertens J, Meersseman P, Megarbane B, Nseir S, van Oers JAH, Reynders M, Rijnders BJA, Schouten JA, Spriet I, Thevissen K, Thille AW, Van Daele R, van de Veerdonk FL, Verweij PE, Wilmer A, Bruggemann RJM, Wauters J; Dutch-Belgian Mycosis Study Group. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial. Intensive Care Med. 2021 Jun;47(6):674-686. doi: 10.1007/s00134-021-06431-0. Epub 2021 May 29.
PubMed 34050768
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase iv, Interventional, Non-blinded, Randomized Controlled Multicenter Study of Posaconazole Prophylaxis for the Prevention of Influenza-associated Aspergillosis (IAA) in Critically Ill Patients
- ClinicalTrials.gov ID
- NCT03378479
- Acronym / sponsor ID
- POSA-FLU / POSA-FLU
- Keywords
- Influenza
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 27 Dec 2017 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 30 Mar 2021 (actual)
- First posted
- 19 Dec 2017 (actual)
- Results
- Posted 8 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to deliver proof of concept that antifungal prophylaxis can reduce the incidence of Influenza Associated Aspergillosis (IAA) in ICU (intensive care unit) patients with severe influenza.
The investigators will perform an interventional non-blinded randomized controlled multicentric proof-of-concept study in patients with severe influenza admitted to the ICU. Patients will be randomized to the posaconazole prophylaxis group or to the SOC (standard of care) group. Oseltamivir will be started at the discretion of the investigator. Patients in the posaconazole group will receive posaconazole prophylaxis for 7 days.
addendum: pharmacokinetics of posaconazole as prophylaxis for invasive fungal disease on ICU
Detailed description
Critically ill patients with PCR-confirmed influenza criteria) are eligible for inclusion in this study and will be randomized to or the posaconazole prophylaxis group or the SOC group.
If a patient is randomized to the posaconazole prophylaxis group, posaconazole (Noxafil, MSD) will be started intravenously from day 1 of randomization (2*300mg( milligram) /d on day 1, followed by 1*300mg/d from day 2 for 7 days) In both patient groups (prophylaxis and SOC) oseltamivir (non-IMP) will be started at the discretion of the treating physician from the first day of ICU admission as 2*150 mg/day for 10 days. If oseltamivir had already been started up before ICU admission, oseltamivir treatment will be continued up to a total of 10 days.
Within 48 hours after influenza diagnosis a bronchoscopy with BAL (bronchoalveolar lavage) and a serum galactomannan will be performed as part of routine ICU care in this type of patients. If an IAA-infection is suspected based on the result of this BAL ((A) Aspergillus cultured from BAL, or (B) a galactomannan (GM)the patient will be withdrawn from the study and antifungal treatment will be started.
addendum: Extensive PK sampling (UZ Leuven and Radboud): full PK curve on day 2 and day 5 (predose, 1.5; 2,3,4,6,8,10,12,18,24 h post infusion).
on non PK days, until day 7, predose sample. PK in BAL fluid only in patients with mechanical ventilation and when medically indicated.
Limited PK sampling: on day 2 and day 5: 1.5-3h, 4-8 h;8-12h; 12-24h post dose. on non PK days: PK pre dose.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOC + 'Posaconazole 18 MG/ML' | Other | Drug: SOC +Posaconazole 18 MG/ML (milligram/milliliter), Other: standard of care (SOC)standard of care (SOC) treatment for influenza pneumonia +posaconazole 2*300mg/d IV on day 1, followed by 1*300mg/d IV from day 2 for 7 days; vials containing 18mg posaconazole /mL, 300mg posaconazole/vial in total) |
| Standard of Care | Other | Other: standard of care (SOC)standard of care treatment for influenza pneumonia (at the investigators discretion) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent must be obtained from the patient or his/her legal representative prior to any study procedures
- Adult patient (≥ 18 years)
- PCR-confirmed influenza based on nasopharyngeal swab (NS), bronchial aspirate (BA) or broncho-alveolar lavage (BAL) within 7 days before ICU admission or within 48 hours after ICU admission. If PCR is not available a positive result of a rapid test is required (a negative rapid test does not imply absence of influenza and thus requires confirmation by PCR)
- Influenza symptoms present for no more than 10 days before ICU admission
- Respiratory distress as the main reason for ICU admission. Respiratory distress will be defined as tachypnea with an respiratory rate ≥ 25x/min and a paO2/fiO2-ratio (fraction of inspired oxygen) ≤ 300 with or without (bilateral) infiltrates.
Key exclusion criteria (10 listed)
- Patients with age < 18 years
- Pregnant women (based on a positive serum sample)
- Expected survival on ICU admission ≤ 48h
- Patients having influenza symptoms for more than 10 days before ICU admission
- Patients being transferred from another hospital ward or another hospital who already have mycological evidence for an IAA-infection (based on sputum, BA or BAL culture, BAL or serum GM)
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 |
|---|---|---|
| SOC +Posaconazole 18 MG/ML (milligram/milliliter)Also: Noxafil.2*300mg/d IV on day 1, followed by 1*300mg/d IV from day 2 for 7 days (total 7 days) | Drug | SOC + 'Posaconazole 18 MG/ML' |
| standard of care (SOC)treatment for influenza pneumonia at the investigators discretion | Other | SOC + 'Posaconazole 18 MG/ML', Standard of Care |
Primary outcome
Number of Participants With IAA-infection at ICU Discharge
Time frame: from date of admission in ICU assessed up to ICU discharge, approximately 21 days
A patient with IAA-infection is defined as a patient having mycological evidence of Aspergillus and at least one Aspergillus compatible sign or symptom and radiological abnormalities
6 secondary outcomes
Time to IAPA Diagnosis
Time frame: from date of inclusion to date of first sign/symptom of IAA infection, assessed up to ICU discharge, approximately 10 days
Length of ICU Stay
Time frame: from date of admission in ICU to date of discharge from ICU, approximately 20 days
Length of Hospital Stay
Time frame: from date of admission in hospital to date of discharge from hospital, approximately 25 days
ICU Mortality - Number of Participant Deaths
Time frame: At ICU discharge
Hospital Mortality - Number of Participant Deaths
Time frame: At hospital discharge
90-day Mortality - Number of Participant Deaths
Time frame: At 90 days after ICU admission
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38828958Elkayal O, Mertens B, Wauters J, Debaveye Y, Rijnders B, Verweij PE, Bruggemann RJ, Spriet I, Dreesen E. Dosing of IV posaconazole to treat critically ill patients with invasive pulmonary aspergillosis: a population pharmacokinetics modelling and simulation study. J Antimicrob Chemother. 2024 Jul 1;79(7):1645-1656. doi: 10.1093/jac/dkae160.
- Derived from this study: PubMed 34050768Vanderbeke L, Janssen NAF, Bergmans DCJJ, Bourgeois M, Buil JB, Debaveye Y, Depuydt P, Feys S, Hermans G, Hoiting O, van der Hoven B, Jacobs C, Lagrou K, Lemiale V, Lormans P, Maertens J, Meersseman P, Megarbane B, Nseir S, van Oers JAH, Reynders M, Rijnders BJA, Schouten JA, Spriet I, Thevissen K, Thille AW, Van Daele R, van de Veerdonk FL, Verweij PE, Wilmer A, Bruggemann RJM, Wauters J; Dutch-Belgian Mycosis Study Group. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial. Intensive Care Med. 2021 Jun;47(6):674-686. doi: 10.1007/s00134-021-06431-0. Epub 2021 May 29.
- Individual participant dataSharing planned: Undecided
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.
Joost Wauters, Phd principal investigator
UZ Leuven
Paul Verweij, Phd principal investigator
Radboud University Medical Center
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing SOC +Posaconazole 18 MG/ML (milligram/milliliter) in people with Aspergillosis; Pulmonary, Invasive (Etiology), run by Universitaire Ziekenhuizen KU Leuven at 12 sites in 3 countries.
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 5 inclusion and 10 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 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Netherlands, Belgium, France. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With IAA-infection at ICU Discharge (time frame: from date of admission in ICU assessed up to ICU discharge, approximately 21 days). 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 NCT03378479, which also lists 2 linked publications.
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 8 Apr 2025.