Prospective Observational Trial of IAPA

Study Overview
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Brief Summary
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A prospective multi-center observational study to assess the incidence of influenza-associated pulmonary aspergillosis (IAPA) in ICU patients and to identify host- and pathogen related risk factors for IAPA in EORTC negative ICU patients with severe influenza.

Detailed Description
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Invasive pulmonary aspergillosis was shown to be a complication of severe influenza infections in immunocompromised patients as well as in immunocompetent patients and is associated with a high mortality. Antifungal prophylaxis might prevent influenza-associated pulmonary aspergillosis (IAPA) and thus might improve the outcome in patients with severe influenza. However, clinical related risk factors should be identified to assess whether a patient will benefit from antifungal prophylaxis. This prospective multi-center observational study will assess the incidence of influenza-associated pulmonary aspergillosis (IAPA) in ICU patients in 12 ICUs in The Netherlands, Belgium and France over 4 influenza seasons. The secondary objective of this study is to identify host- and pathogen related risk factors for IAPA in EORTC negative ICU patients with severe influenza. Patients aged 18 or older admitted to the intensive care unit (ICU) during the inclusion period due severe influenza without classic risk factors defined by the EORTC will be included.

Official Title
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Influenza-associated Pulmonary Aspergillosis (IAPA) in ICU Patients With Severe Influenza: Incidence and Host- and Pathogen Related Risk Factors

Conditions
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Influenza With Pneumonia, Pulmonary Aspergillosis

Intervention / Treatment
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* Other: Identification of biomarkers for IAPA via patient sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a PCR-positive respiratory virus panel (RVP) result for influenza within 96 hours before or 48 hours after ICU admission. Patients who require ICU admission for more than 24 hours for severe influenza. Patients who have respiratory distress (respiratory rate >= 25x/minute and paO2/fiO2 < 300 with or without bilateral infiltrates) as the main reason for ICU admission. Patients who do not have an EORTC host factor. Patients who are at least 18 years of age. Exclusion Criteria: Patients with age < 18 years as extensive sampling is required Expected survival on ICU admission ≤ 48h Patients that are being treated actively with antifungal agents for invasive aspergillosis. Patients or their legal representatives who did not sign the informed consent form

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IAPA+<br>Influenza patients who develop IAPA during ICU admission | Other: Identification of biomarkers for IAPA via patient sampling<br>* Blood, BAL, microbiome<br>|
| IAPA-<br>Influenza patients admitted to the ICU not developing IAPA | Other: Identification of biomarkers for IAPA via patient sampling<br>* Blood, BAL, microbiome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of IAPA-infection at ICU discharge | The diagnosis of IAPA will be made by the treating physician, according to a strict case definition. | from date of admission in ICU assessed up to ICU discharge, approximately 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to IAPA diagnosis | The diagnosis of IAPA will be made by the treating physician, according to a strict case definition. | from date of admission in ICU assessed up to ICU discharge, approximately 21 days | 
| Length of ICU stay |  | from date of admission in ICU assessed up to ICU discharge, approximately 21 days | 
| Length of hospital stay |  | from date of admission in hospital assessed up to hospital discharge, approximately 30 days | 
| ICU mortality |  | up to ICU discharge, approximately 21 days | 
| Hospital mortality |  | from date of admission in hospital assessed up to hospital discharge, approximately 30 days | 
| 30-day mortality |  | 30 days | 
| 90-day mortality |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Intensive Care Unit, Influenza-associated pulmonary aspergillose, Invasive Pulmonary Aspergillosis, Virus Diseases, Respiratory tract infections, Fungal Lung Diseases