Posaconazole Prophylaxis for CAPA Prevention in Critically-Ill Patients (POSACOVID)

Posaconazole for the Prevention of COVID-19 Associated Pulmonary Aspergillosis in Critically-Ill Patients: A European Multicenter Case-Control Study

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.

Study Overview

• Status: Completed
• Conditions: Aspergillosis; COVID-19 Respiratory Infection
• Intervention / Treatment: Drug: Posaconazole

• Study Type: Observational
• Enrollment (Actual): 249

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University of Graz
• France
  • Rennes, France, 35033
    • University of Rennes
• Italy
  • Genova, Italy, 16132
    • San Martino Polyclinic Hospital IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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).

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Critically-ill COVID-19 patients receiving posaconazole prophylaxis	Drug: Posaconazole; Intravenous posaconazole prophylaxis
Critically-ill COVID-19 patients without antifungal prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of COVID-19 associated pulmonary aspergillosis (CAPA)	Compare the incidence of CAPA at time of discharge from the ICU in those who received posaconazole compared to controls who did not	ICU admission to ICU discharge. On average 20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at ICU discharge	Compare the rates of survival at time of discharge from the ICU in those who receive posaconazole compared to those who do not	ICU admission to ICU discharge. On average 20 days
Length of ICU stay	Compare the length of ICU stay in those who receive posaconazole compared to those who do not	ICU admission to ICU discharge. On average 20 days
Mortality rate at 30 days	Compare the mortality rate at 30 days in those who receive posaconazole compared to those who do not	ICU admission until 30 days after ICU admission
Mortality rate at 90 days	Compare the mortality rate at 90 days in those who receive posaconazole compared to those who do not	ICU admission until 90 days after ICU admission

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): August 23, 2023
• Study Completion (Actual): August 23, 2023

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Bacterial Infections and Mycoses; Mycoses; COVID-19; Respiratory Tract Infections; Aspergillosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: 32-296 ex 19/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No