Posaconazole for the Prevention of Influenza-associated Aspergillosis in Critically Ill Patients

NCT03378479 | Completed Phase 4 Results

• 1 other identifier: POSA-FLU
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 12

Brief 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. 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

Conditions

Aspergillosis; Pulmonary, Invasive (Etiology)

Keywords

Influenza

Outcome Measures

Primary Outcomes (1)

• 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

  from date of admission in ICU assessed up to ICU discharge, approximately 21 days

Secondary Outcomes (6)

• Time to IAPA Diagnosis

  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

  from date of admission in ICU to date of discharge from ICU, approximately 20 days

• Length of Hospital Stay

  from date of admission in hospital to date of discharge from hospital, approximately 25 days

• ICU Mortality - Number of Participant Deaths

  At ICU discharge

• Hospital Mortality - Number of Participant Deaths

  At hospital discharge

Study Arms (2)

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)

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)

Other: standard of care (SOC)

Interventions

SOC +Posaconazole 18 MG/ML (milligram/milliliter) DRUG

.2\*300mg/d IV on day 1, followed by 1\*300mg/d IV from day 2 for 7 days (total 7 days)

Also known as: Noxafil

SOC + 'Posaconazole 18 MG/ML'

standard of care (SOC) OTHER

treatment for influenza pneumonia at the investigators discretion

SOC + 'Posaconazole 18 MG/ML'; Standard of Care

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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 -

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

AZ Sint Jan

Bruges, 8000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

CHU Lille

Lille, 59000, France

Location

Hospital Lariboisière

Paris, 75010, France

Location

Hospital Saint-Louis

Paris, 75010, France

Location

UMC Maastricht

Maastricht, 6229, Netherlands

Location

UMC Radboud

Nijmegen, 6500, Netherlands

Location

Canisius Wilhelmina Hospital

Nijmegen, 6532, Netherlands

Location

MC Erasmus

Rotterdam, 3015, Netherlands

Location

Elisabeth-TweeSteden Hospital

Tilburg, 5042, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 38828958 DERIVED

• Vanderbeke 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.

  PMID: 34050768 DERIVED

MeSH Terms

Conditions

Aspergillosis; Influenza, Human

Interventions

Magnesium; posaconazole; Standard of Care

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals, Light; Metals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Prof. Dr. Joost Wauters - Intensivist
• Organization: UZ Leuven

joost.wauters@uzleuven.be

016344275

Study Officials

• Joost Wauters, Phd

  UZ Leuven

  PRINCIPAL INVESTIGATOR

• Paul Verweij, Phd

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: December 19, 2017
• Study Start: December 27, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 30, 2021
• Last Updated: April 8, 2025
• Results First Posted: April 8, 2025

Record last verified: 2025-03

Locations

FR (3); NL (5); BE (4)