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Isavuconazole for the Prevention of COVID-19-associated Pulmonary Aspergillosis (Isavu-CAPA)

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ClinicalTrials.gov Identifier: NCT04707703
Recruitment Status : Not yet recruiting
First Posted : January 13, 2021
Last Update Posted : January 13, 2021
Sponsor:
Collaborator:
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
Jeffrey Jenks, MD, MPH, University of California, San Diego

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Severe Acute Respiratory Syndrome Coronavirus 2 Aspergillosis Invasive Drug: Isavuconazonium Injection [Cresemba] Drug: Placebo Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Isavuconazole for the Prevention of SARS-CoV-2-associated Invasive Aspergillosis in Critically-Ill Patients
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : March 2022


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
Drug: Isavuconazonium Injection [Cresemba]
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:
  • Isavuconazole
  • Cresemba

Placebo Comparator: SOC plus Placebo
SOC plus intravenous placebo every 8 hours for 6 doses followed by once daily for up to 28 days
Drug: Placebo
Intravenous placebo every 8 hours for 6 doses followed by intravenous placebo once daily for up to 28 days




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04707703


Contacts
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Contact: Jeffrey Jenks, MD, MPH 1-800-926-8273 jjenks@health.ucsd.edu

Locations
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United States, California
University of California Irvine
Orange, California, United States, 92868
Contact: Alpesh Amin, MD, MBA       anamin@hs.uci.edu   
Contact: Lanny Hsieh, MD       llhsieh@hs.uci.edu   
University of California Davis
Sacramento, California, United States, 95817
Contact: George Thompson, MD       grthompson@ucdavis.edu   
University of California San Diego
San Diego, California, United States, 92103
Contact: Jeffrey Jenks, MD, MPH       jjenks@health.ucsd.edu   
Contact: Robert Owens, MD       rowens@health.ucsd.edu   
Sponsors and Collaborators
Jeffrey Jenks, MD, MPH
Astellas Pharma Global Development, Inc.
Investigators
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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
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Responsible Party: Jeffrey Jenks, MD, MPH, Assoc Physician, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04707703    
Other Study ID Numbers: 200639
First Posted: January 13, 2021    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jeffrey Jenks, MD, MPH, University of California, San Diego:
Isavuconazole
Antifungal Agents
Anti-infective Agents
Coronavirus-associated Invasive Pulmonary Aspergillosis
CAPA
Additional relevant MeSH terms:
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Aspergillosis
Pulmonary Aspergillosis
Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Mycoses
Respiratory Tract Infections
Respiratory Tract Diseases
Lung Diseases, Fungal
Lung Diseases
Isavuconazole
Antifungal Agents
Anti-Infective Agents