The objective of this study is to evaluate whether antifungal prophylaxis with isavuconazole can reduce the incidence of SARS-CoV-2-associated invasive aspergillosis in patients in the ICU (intensive care unit) with severe COVID-19 infection. The investigators will perform an interventional, double-blinded, randomized-controlled, multi-center study in patients with severe COVID-19 infection admitted to the ICU. Patients will be randomized to the isavuconazole prophylaxis plus standard of care (SOC) group or the placebo plus SOC group. Participants will receive isavuconazole or placebo for up to 28 days or until discharge from the hospital (whichever occurs first).
Adult patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 (COVID-19) infection without a diagnosis of invasive aspergillosis who are hospitalized in the ICU are eligible for inclusion in this study and will be randomized to the isavuconazole plus standard of care (SOC) group or placebo plus SOC group. If randomized to the isavuconazole group, participants will receive intravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by intravenous isavuconazonium sulfate 372 mg once daily for up to 28 days. If randomized to the placebo group, participants will receive intravenous placebo every 8 hours for 6 doses followed by once daily for up to 28 days. Both groups will receive the usual SOC. Following randomized to the two treatment arms, participants will be screened for invasive aspergillosis with thrice weekly fungal cultures from tracheal aspirate (TA) secretions or thrice weekly serum galactomannan (GM) testing (if TA unable to be performed, contraindicated, or participant is not intubated). If invasive aspergillosis or other invasive fungal infection is detected, antifungal therapy will be initiated (if the participant is in the placebo arm) or modified if needed (if the participant is in the isavuconazole arm).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
8
Intravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by intravenous isavuconazonium sulfate 372 mg once daily for up to 28 days
Intravenous placebo every 8 hours for 6 doses followed by intravenous placebo once daily for up to 28 days
University of California Irvine
Orange, California, United States
University of California Davis
Sacramento, California, United States
University of California San Diego
San Diego, California, United States
The incidence of SARS-CoV-2-associated invasive aspergillosis at time of ICU discharge
A patient with SARS-CoV-2-associated invasive aspergillosis is defined as a patient having COVID-19 infection needing intensive care, mycological evidence of Aspergillus and compatible radiological abnormalities consistent with pulmonary aspergillosis
Time frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
The incidence of SARS-CoV-2-associated non-Aspergillus invasive fungal infections at time of ICU discharge
A patient with SARS-CoV-2-associated non-Aspergillus invasive fungal infection is defined as a patient having COVID-19 infection needing intensive care, mycological evidence of a non-Aspergillus invasive fungal infection, and compatible radiological abnormalities consistent with non-Aspergillus invasive fungal infection
Time frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
Survival
Compare the rates of survival at time of discharge from the ICU in those who receive isavuconazole compared to those who receive placebo
Time frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
Length of ICU stay
Compare the length of ICU stay in those who receive isavuconazole compared to those who receive placebo
Time frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
Length of Hospital stay
Compare the length of hospital stay in those who receive isavuconazole compared to those who receive placebo
Time frame: From date of admission in ICU assessed up to hospital discharge, approximately 32 days
Mortality
Compare the mortality rate at 30 and 90 days in those who receive isavuconazole compared to those who receive placebo
Time frame: At 30 and 90 days
Adverse events
Compare the rates of adverse events in those who receive isavuconazole compared to those who receive placebo
Time frame: From date of start of isavuconazole or placebo through duration of isavuconazole or placebo, approximately 28 days
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