- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04707703
Isavuconazole for the Prevention of COVID-19-associated Pulmonary Aspergillosis (Isavu-CAPA)
Isavuconazole for the Prevention of SARS-CoV-2-associated Invasive Aspergillosis in Critically-Ill Patients
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).
Study Overview
Status
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
California
-
Orange, California, United States, 92868
- University of California Irvine
-
Sacramento, California, United States, 95817
- University of California Davis
-
San Diego, California, United States, 92103
- University of California San Diego
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent obtained from the patient or his/her legally authorized person.
- Adult patient (> 18 years).
- PCR-confirmed SARS-CoV-2 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.
- Radiographic imaging consistent with SARS-CoV-2 infection (e.g. atypical pneumonia, organizing pneumonia, ground glass opacities) or acute respiratory distress syndrome (ARDS) within 7 days of diagnosis of SARS-CoV-2 infection.
- A negative pregnancy test in women of child-bearing age.
- If a woman is of child-bearing age, she must be willing to use an effective method of contraception for 28 days after the final dose of isavuconazole per manufacturer instructions
Exclusion Criteria:
- Anticipated transfer to another medical center that is not a study site within hours of admission to the ICU.
- Pregnancy based on a positive human chorionic gonadotropin (HCG) test from serum or urine.
- Patient who is breastfeeding and unable to discontinue breastfeeding while taking the study drug.
- Patients with a diagnosis of invasive aspergillosis/detection of Aspergillus spp. by culture from sputum, TA, BA, or BALF or positive GM from serum or BALF at time of screening or randomization.
- History of invasive aspergillosis within the prior six months.
- Patients with a known intolerance or hypersensitivity to isavuconazole or other azole agents.
- History of familial short QT syndrome.
- Patients that are being treated with mold-active antifungal agents for invasive aspergillosis or another invasive fungal infection.
- Patients with severe hepatic impairment or liver cirrhosis (Child C) should be excluded from the study unless the treating physicians feel the benefits of treatment outweigh the risks.
- Treatment with Lopinavir/ritonavir for HIV infection.
- Prohibited Medications
- Co-administration with a strong CYP3A4 inhibitor or high-dose ritonavir as they may alter the plasma concentration of isavuconazole.
- Co-administration with a strong CYP3A4 inducer such as rifampin, carbamazepine, St. John's wort, or long acting barbiturates.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SOC plus Isavuconazonium sulfate
SOC plus intravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by 372mg once daily for up to 28 days
|
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
Other Names:
|
Placebo Comparator: SOC plus Placebo
SOC plus intravenous placebo every 8 hours for 6 doses followed by 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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The incidence of SARS-CoV-2-associated invasive aspergillosis at time of ICU discharge
Time Frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
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
|
From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The incidence of SARS-CoV-2-associated non-Aspergillus invasive fungal infections at time of ICU discharge
Time Frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
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
|
From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
Survival
Time Frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
Compare the rates of survival at time of discharge from the ICU in those who receive isavuconazole compared to those who receive placebo
|
From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
Length of ICU stay
Time Frame: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
Compare the length of ICU stay in those who receive isavuconazole compared to those who receive placebo
|
From date of admission in ICU assessed up to ICU discharge, approximately 28 days
|
Length of Hospital stay
Time Frame: From date of admission in ICU assessed up to hospital discharge, approximately 32 days
|
Compare the length of hospital stay in those who receive isavuconazole compared to those who receive placebo
|
From date of admission in ICU assessed up to hospital discharge, approximately 32 days
|
Mortality
Time Frame: At 30 and 90 days
|
Compare the mortality rate at 30 and 90 days in those who receive isavuconazole compared to those who receive placebo
|
At 30 and 90 days
|
Adverse events
Time Frame: From date of start of isavuconazole or placebo through duration of isavuconazole or placebo, approximately 28 days
|
Compare the rates of adverse events in those who receive isavuconazole compared to those who receive placebo
|
From date of start of isavuconazole or placebo through duration of isavuconazole or placebo, approximately 28 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffrey Jenks, MD, MPH, University of California, San Diego
- Study Chair: George Thompson, MD, University of California, Davis
- Study Chair: Martin Hoenigl, MD, University of California, San Diego
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Bacterial Infections and Mycoses
- Mycoses
- Lung Diseases, Fungal
- Severe Acute Respiratory Syndrome
- Coronavirus Infections
- Aspergillosis
- Pulmonary Aspergillosis
- Anti-Infective Agents
- Antifungal Agents
- Isavuconazole
Other Study ID Numbers
- 200639
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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