Prevention of influenza-associated aspergillosis in critically ill patients with Posaconazole

Phase 1

Conditions: Invasive aspergillosis in critically ill patients with influenza pneumonia
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2017-003270-14-NL

Lead Sponsor: Radboud University Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 88

Inclusion Criteria

1. Written informed consent must be obtained from the patient or his/her legal representative prior to any study procedures
2. Adult patient (= 18 years)
3. PCR-confirmed influenza based on nasopharyngeal swab (NS), bronchial aspirate (BA) or broncho-alveolar lavage (BAL) fluid within 7 days before ICU admission or within 48 hours after ICU admission. If PCR is not available, a positive result of a rapid antigen test is required (a negative rapid antigen test does not imply absence of influenza and thus requires confirmation by PCR)
4. Influenza symptoms present for no more than 10 days before ICU admission
5. Respiratory distress as the main reason for ICU admission. Respiratory distress will be defined as tachypnea with a respiratory rate = 25x/min. and a PaO2/FiO2-ratio = 300 with or without (bilateral) infiltrates on radiographic chest studies
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

1. Pregnant women (based on a positive serum sample )
2. Expected survival on ICU admission = 48h
3. Patients being transferred from another hospital ward or another hospital who already have mycological evidence of IA (based on sputum, BA or BAL fluid culture, BAL fluid or serum GM; also see 2.3 Primary Endpoints for a definition of IA)
4. Patients with known intolerance of or hypersensitivity to posaconazole
5. Patients actively treated with antifungal agents with activity against Aspergillus species
6. Patients actively treated with rifampicin or rifabutin
7. Patients with a QTc interval = 500 milliseconds on electrocardiography (ECG)
8. Patients with liver cirrhosis (Child-Pugh classification C)
9. Participation in another interventional clinical trial
10. Any disorder which, in the investigator’s opinion, might jeopardize subject’s safety or compliance with the protocol when participating in this study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To deliver proof of concept that antifungal prophylaxis can reduce the incidence of influenza-associated aspergillosis (IAA) in ICU patients;Secondary Objective: To assess immunological response parameters and frequency of certain single nucleotide polymorphisms (SNPs) and mutations in DNA leading to increased susceptibility to aspergillosis in patients with influenza;Primary end point(s): Incidence of influenza-associated aspergillosis (IAA) at ICU discharge;Timepoint(s) of evaluation of this end point: ICU discharge

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: - IAA diagnosis<br>- ICU discharge<br>- Hospital discharge<br>- Day 30<br>- Day 90<br>- During ICU stay<br>- End of study;Secondary end point(s): - Time to IAA diagnosis<br>- Length of ICU stay<br>- Length of hospital stay<br>- Overall mortality<br>- 30 day mortality<br>- 90 day mortality<br>- Presence or absence of markers for macrophage activation syndrome (MAS)<br>- Immunological response parameters (cytokine production and reactive oxygen species production)<br>- Frequency of single nucleotide polymorphisms/mutations in relevant genes

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