Aspergillosis, COVID-19 Respiratory Infection
Conditions
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.
Interventions
DRUGPosaconazole
Intravenous posaconazole prophylaxis
Sponsors
Merck Sharp & Dohme LLC
Medical University of Graz
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of COVID-19 Associated Pulmonary Aspergillosis (CAPA) | ICU admission to ICU discharge. On average 20 days | Compare the incidence of CAPA at time of discharge from the ICU in those who received posaconazole compared to controls who did not |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Risk Factors for CAPA Development (EORTC/MSGERC) | ICU admission to ICU discharge. On average 20 days | This Outcome Measure examines whether the presence of an EORTC/MSGERC-defined risk factor at ICU admission is associated with an increased risk of developing COVID-19-associated pulmonary aspergillosis (CAPA) during the ICU stay. The analysis is conducted using a cohort of patients admitted to the ICU, tracking the development of CAPA from ICU admission to ICU discharge. For this purpose, the number of subjects who had underlying EORTC/MSGERC risk factors present at ICU admission was collected and used as a parameter in a multivariate logistic model to assess the association with an increased risk for CAPA development. |
| Risk Factors for CAPA Development (ECMO) | ICU admission to ICU discharge. On average 20 days | This Outcome Measure examines whether the need for extracorporal membrange oxygenation (ECMO) treatment during ICU admission is associated with an increased risk of developing COVID-19-associated pulmonary aspergillosis (CAPA) during the ICU stay. The analysis is conducted using a cohort of patients admitted to the ICU, tracking the development of CAPA from ICU admission to ICU discharge. For this purpose, the number of subjects who required ECMO treatment during ICU stay was collected and used as a parameter in a multivariate logistic model to assess the association with an increased risk for CAPA development. |
Countries
Austria, France, Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COVID-19 Patients With Acute Respiratory Failure Receiving Posaconazole Prophylaxis (Center 1) Cases: Subjects with COVID-19 associated ARF who received intravenous posaconazole prophylaxis upon ICU admission in addition to standard of care treatment | 83 |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 2) Controls: Subjects with COVID-19 associated ARF who did not receive antifungal prophylaxis in addition to standard of care treatment | 83 |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 3) Controls: Subjects with COVID-19 associated ARF who did not receive antifungal prophylaxis in addition to standard of care treatment | 83 |
| Total | 249 |
Baseline characteristics
| Characteristic | COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 2) | COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 3) | Total | COVID-19 Patients With Acute Respiratory Failure Receiving Posaconazole Prophylaxis (Center 1) |
|---|---|---|---|---|
| Age, Continuous | 65 years | 66 years | 65 years | 65 years |
| Race (NIH/OMB) American Indian or Alaska Native | — | — | 0 Participants | — |
| Race (NIH/OMB) Asian | — | — | 0 Participants | — |
| Race (NIH/OMB) Black or African American | — | — | 0 Participants | — |
| Race (NIH/OMB) More than one race | — | — | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | — | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | — | — | 0 Participants | — |
| Race (NIH/OMB) White | — | — | 0 Participants | — |
| Region of Enrollment Austria | 0 participants | 0 participants | 83 participants | 83 participants |
| Region of Enrollment France | 0 participants | 83 participants | 83 participants | 0 participants |
| Region of Enrollment Italy | 83 participants | 0 participants | 83 participants | 0 participants |
| Sex: Female, Male Female | 55 Participants | 54 Participants | 165 Participants | 56 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 84 Participants | 27 Participants |
| Systemic glucocorticoid treatment | 83 Participants | 83 Participants | 249 Participants | 83 Participants |
| Tocilizumab Treatment | 3 Participants | 1 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 60 / 83 | 14 / 83 | 38 / 83 |
| other Total, other adverse events | 0 / 83 | 0 / 83 | 0 / 83 |
| serious Total, serious adverse events | 83 / 83 | 83 / 83 | 83 / 83 |
Outcome results
Primary
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
Time frame: ICU admission to ICU discharge. On average 20 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COVID-19 Patients With Acute Respiratory Failure Receiving Posaconazole Prophylaxis (Center 1) | Incidence of COVID-19 Associated Pulmonary Aspergillosis (CAPA) | 1.69 Cases per 1000 ICU days |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 2) | Incidence of COVID-19 Associated Pulmonary Aspergillosis (CAPA) | 0.84 Cases per 1000 ICU days |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 3) | Incidence of COVID-19 Associated Pulmonary Aspergillosis (CAPA) | 7.18 Cases per 1000 ICU days |
Secondary
Risk Factors for CAPA Development (ECMO)
This Outcome Measure examines whether the need for extracorporal membrange oxygenation (ECMO) treatment during ICU admission is associated with an increased risk of developing COVID-19-associated pulmonary aspergillosis (CAPA) during the ICU stay. The analysis is conducted using a cohort of patients admitted to the ICU, tracking the development of CAPA from ICU admission to ICU discharge. For this purpose, the number of subjects who required ECMO treatment during ICU stay was collected and used as a parameter in a multivariate logistic model to assess the association with an increased risk for CAPA development.
Time frame: ICU admission to ICU discharge. On average 20 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVID-19 Patients With Acute Respiratory Failure Receiving Posaconazole Prophylaxis (Center 1) | Risk Factors for CAPA Development (ECMO) | 13 Participants |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 2) | Risk Factors for CAPA Development (ECMO) | 2 Participants |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 3) | Risk Factors for CAPA Development (ECMO) | 4 Participants |
Secondary
Risk Factors for CAPA Development (EORTC/MSGERC)
This Outcome Measure examines whether the presence of an EORTC/MSGERC-defined risk factor at ICU admission is associated with an increased risk of developing COVID-19-associated pulmonary aspergillosis (CAPA) during the ICU stay. The analysis is conducted using a cohort of patients admitted to the ICU, tracking the development of CAPA from ICU admission to ICU discharge. For this purpose, the number of subjects who had underlying EORTC/MSGERC risk factors present at ICU admission was collected and used as a parameter in a multivariate logistic model to assess the association with an increased risk for CAPA development.
Time frame: ICU admission to ICU discharge. On average 20 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVID-19 Patients With Acute Respiratory Failure Receiving Posaconazole Prophylaxis (Center 1) | Risk Factors for CAPA Development (EORTC/MSGERC) | 8 Participants |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 2) | Risk Factors for CAPA Development (EORTC/MSGERC) | 7 Participants |
| COVID-19 Patients With Acute Respiratory Failure Without Antifungal Prophylaxis (Center 3) | Risk Factors for CAPA Development (EORTC/MSGERC) | 4 Participants |