E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive aspergillosis in critically ill patients with influenza pneumonia |
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E.1.1.1 | Medical condition in easily understood language |
Aspergillosis as a superinfection of severe influenza |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To deliver proof of concept that antifungal prophylaxis can reduce the incidence of influenza-associated aspergillosis (IAA) in ICU patients |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of influenza-associated aspergillosis (IAA) at ICU discharge |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time to IAA diagnosis
- Length of ICU stay
- Length of hospital stay
- Overall mortality
- 30 day mortality
- 90 day mortality
- Presence or absence of markers for macrophage activation syndrome (MAS)
- Immunological response parameters (cytokine production and reactive oxygen species production)
- Frequency of single nucleotide polymorphisms/mutations in relevant genes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- IAA diagnosis
- ICU discharge
- Hospital discharge
- Day 30
- Day 90
- During ICU stay
- End of study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No prophylactic treatment/standard of care |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |