Clinical trial NCT04848831: Diagnosis of Invasive Pulmonary Aspergillosis, Specific Testing in Bronchial Secretions Versus Bronchoalveolar Fluid
Official title: Diagnosis of Invasive Pulmonary Aspergillosis (IPA) - Specific Testing in Bronchial Secretions Versus Bronchoalveolar Fluid in Patients With and Without COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Invasive Pulmonary Aspergillosis
Keywords: IPA
Aspergillus
Galactomannan
Aspergillus PCR
Aspergillus LFA
Bronchoscopy
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2021-04-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 4) Suspicion of invasive pulmonary aspergillosis:

(a) Clinical:

* Neutropenia
* Hematooncological disease
* Allogeneic stem cell transplantation
* Organ transplantation
* SARS-CoV-2
* Influenza

  b) Radiological:
* Aspergillus typical findings on computed tomography.

  c) Microbiological:
* Aspergillus positive findings from respiratory tract secretions (culture, galactomannan, PCR) or d) Confirmed invasive pulmonary aspergillosis.

Brief summary: The aim of this research project is to compare the results of Aspergillus specific test methods Aspergillus Galactomannan Enzyme Immunoassay (GM-EIA), Aspergillus polymerase chain reaction (PCR), Aspergillus Galactomannan Lateral Flow Assay (LFA) from different respiratory tract secretions. The bronchoalveolar lavage (BAL) fluid and bronchial secretions (NBL) are compared in the same examination for each patient.

Detailed description: Invasive pulmonary Infection with Aspergillus species has emerged as one of the most common causes of infectious death in critically ill patients (38%-79%). The incidence of invasive pulmonary Aspergillosis (IPA) in intensive care units is still not sufficiently clear and ranges between 0.3 % and 19 %. In the last two decades, IPA has been documented as an emerging disease in ICU patients without classic risk factors. The establishment of new therapeutic options in oncology with small-molecule kinase inhibitors (SMKI) and CAR (chimeric antigen receptor) T cell therapy have also led to an increase in IPA. Furthermore, during the influenza epidemics since 2009 and during the SARS-CoV-2 pandemic, IPA was observed in COVID-19 patients without classic risk factors. The cultural detection of molds can take between several days and up to 2 weeks, as this is a slow growing fungus. An Aspergillus Galactomannan EIA (enzyme immunoassay), an Aspergillus PCR (polymerase chain reaction) examination of the respiratory tract material is already available after 4-24 hours. A test using Aspergillus Galactomannan LFA (lateral flow assay) or LFD (lateral flow device) even furthers reduces this interval to 45 minutes. These tests allow the attending physician to initiate a much faster antimycotic treatment. Up to now, the samples for these examinations have been routinely obtained from bronchoscopically obtained bronchoalveolar lavage fluids. In this bronchoalveolar lavage (BAL), body-warm saline solution (NaCl) is instilled into segmental ostia of the lung and immediately re-aspirated . However, there are first indications that examinations from bronchial secretions using deep suction without bronchoscopy achieve similar results to the examination of the BAL. The bronchoscopic diagnosis in COVID-19 patients is probably associated with an increased risk of infection for the examiner due to the aerosol formation during this examination. Two studies from the first wave of the SARS-CoV-2 pandemic have therefore used secretions from the bronchial system = non-bronchoscopic lavage (NBL) to diagnose IPA. This method appears to be reasonable save, appropriate and less risky, but has never been scientifically validated for aspergillus infections. It is not yet clear whether the Aspergillus Galactomannan EIA, the Aspergillus PCR test and the Aspergillus LFA test provide comparable or transmissible results in both lung compartments. A direct comparison of the test results of the bronchoalveolar lavage (BAL) and the bronchial secretion (NBL) have not been described in the literature.

Study Design:

Monocentric prospective exploratory (and in the course confirmatory) cohort study.

1. st pilot phase: Pilot study to test the feasibility and to gain information for the case number calculation of a subsequent larger prospective study.
2. nd study phase: The statistically calculated number of patients who undergo a bronchoscopy during their stay at the UKE and who are urgently suspected of having IPA or who are confirmed to have IPA will be examined for bronchial secretions (NBL) and BAL fluids.

Eligibility criteria: Inclusion Criteria:

1. Age: at least 18 years
2. Consent to prospective data collection.
3. Clinical need for bronchoscopic examination.

Exclusion Criteria:

Refusal of consent to study participation

Primary outcomes:
measure: Equivalence of quantitative results of Aspergillus galactomannan EIA examination from bronchial secretions (NBL) and BAL in one patient.
timeFrame: The observation period for each individual patient begins with bronchoscopic examination (day 0) and ends after 90 days (day 90).
Secondary outcomes:
measure: Number of matched results (within a study participant) of Aspergillus PCR examination from BAL and NBL.
timeFrame: The observation period for each individual patient begins with bronchoscopic examination (day 0) and ends after 90 days (day 90).
measure: Number of matched results (within a study participant) of Aspergillus galactomannan LFA examination from BAL and NBL.
timeFrame: The observation period for each individual patient begins with bronchoscopic examination (day 0) and ends after 90 days (day 90).
Other outcomes:
Locations:
Study officials:
affiliation: University Medical Center Hamburg-Eppendorf, Germany
name: Maria Schroeder, MD
role: PRINCIPAL_INVESTIGATOR
References:
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