Clinical trial NCT05065658: Posaconazole Prophylaxis for CAPA Prevention in Critically-Ill Patients
Official title: Posaconazole for the Prevention of COVID-19 Associated Pulmonary Aspergillosis in Critically-Ill Patients: A European Multicenter Case-Control Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19 Respiratory Infection
Aspergillosis
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-10-04
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be comprised of patients admitted to the ICU because of severe SARS-CoV-2 infections, who are requiring mechanical ventilation and receive dexamethasone as part of their COVID-19 ARDS treatment in medical centers in i) Graz, Austria (cases), and ii) Genoa, Italy, and iii) Rennes, France (all controls).

Posaconazole prophylaxis for ICU patients with severe COVID-19 requiring ICU admission due to ARDS has been introduced in Graz in July 2020, and cases from Graz will be matched with controls from Rennes and Genoa (matching for days on mechanical ventilation at baseline, Apache II score, age, dexamethasone dosage, and underlying disease).

Brief summary: COVID-19 associated pulmonary aspergillosis (CAPA) is considered a potentially life-threatening infection in critically ill COVID (Corona Virus disease)-19 patients. This study will investigate the efficacy of mold-active prophylaxis with posaconazole for patients with severe SARS (severe acute respiratory syndrome)-CoV-2 infection admitted to the ICU (intensive care unit) in a multi-center case-control study in Europe.


Eligibility criteria: Inclusion Criteria:

* Adult patient (\> 18 years)
* PCR (polymerase chain reaction) -confirmed SARS-CoV-2 infections based on nasopharyngeal swab (NPS), oropharyngeal swab (OPS), tracheal aspirate (TA), bronchial aspirate (BA), or bronchoalveolar lavage fluid (BALF) within 14 days prior to ICU admission or within 72 hours following ICU admission due to severe COVID-19 infection
* Radiographic imaging consistent with SARS-CoV-2 infection (e.g. atypical pneumonia, organizing pneumonia, ground glass opacities) or ARDS within 7 days of diagnosis of SARS-CoV-2 infection

Exclusion Criteria:

* Patients with a diagnosis of invasive aspergillosis/detection of Aspergillus spp. by culture from sputum, TA, BA, or BALF or positive GM from serum, TA, or BALF at baseline (=ICU admission)
* History of invasive aspergillosis within the prior six months
* Patients that are being treated with mold-active antifungal agents for invasive aspergillosis or another invasive fungal infection
* Patients that are being treated with mold-active antifungal agents for invasive aspergillosis or another invasive fungal infection
* Death or transfer to general ward within 48 hours of ICU admission
* Antifungal prophylaxis other than posaconazole (e.g. inhaled amphotericin B)

Primary outcomes:
measure: Incidence of COVID-19 Associated Pulmonary Aspergillosis (CAPA)
timeFrame: ICU admission to ICU discharge. On average 20 days
Secondary outcomes:
measure: Risk Factors for CAPA Development (EORTC/MSGERC)
timeFrame: ICU admission to ICU discharge. On average 20 days
measure: Risk Factors for CAPA Development (ECMO)
timeFrame: ICU admission to ICU discharge. On average 20 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
state: Styria
city: Rennes
country: France
facility: University of Rennes
city: Genova
country: Italy
facility: San Martino Polyclinic Hospital IRCCS
Study officials:
References: