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

Primary Purpose

Severe Acute Respiratory Syndrome Coronavirus 2, Aspergillosis Invasive

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Isavuconazonium Injection [Cresemba]
Placebo
Sponsored by
Jeffrey Jenks, MD, MPH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Severe Acute Respiratory Syndrome Coronavirus 2 focused on measuring Isavuconazole, Antifungal Agents, Anti-infective Agents, Coronavirus-associated Invasive Pulmonary Aspergillosis, CAPA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California Irvine
  • University of California Davis
  • University of California San Diego

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SOC plus Isavuconazonium sulfate

SOC plus Placebo

Arm Description

SOC plus intravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by 372mg once daily for up to 28 days

SOC plus intravenous placebo every 8 hours for 6 doses followed by once daily for up to 28 days

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Survival
Compare the rates of survival at time of discharge from the ICU in those who receive isavuconazole compared to those who receive placebo
Length of ICU stay
Compare the length of ICU stay in those who receive isavuconazole compared to those who receive placebo
Length of Hospital stay
Compare the length of hospital stay in those who receive isavuconazole compared to those who receive placebo
Mortality
Compare the mortality rate at 30 and 90 days in those who receive isavuconazole compared to those who receive placebo
Adverse events
Compare the rates of adverse events in those who receive isavuconazole compared to those who receive placebo

Full Information

First Posted
January 8, 2021
Last Updated
November 23, 2022
Sponsor
Jeffrey Jenks, MD, MPH
Collaborators
Astellas Pharma Global Development, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04707703
Brief Title
Isavuconazole for the Prevention of COVID-19-associated Pulmonary Aspergillosis
Acronym
Isavu-CAPA
Official Title
Isavuconazole for the Prevention of SARS-CoV-2-associated Invasive Aspergillosis in Critically-Ill Patients
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Participant enrollment challenges
Study Start Date
March 16, 2021 (Actual)
Primary Completion Date
October 25, 2021 (Actual)
Study Completion Date
October 25, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jeffrey Jenks, MD, MPH
Collaborators
Astellas Pharma Global Development, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Acute Respiratory Syndrome Coronavirus 2, Aspergillosis Invasive
Keywords
Isavuconazole, Antifungal Agents, Anti-infective Agents, Coronavirus-associated Invasive Pulmonary Aspergillosis, CAPA

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SOC plus Isavuconazonium sulfate
Arm Type
Experimental
Arm Description
SOC plus intravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by 372mg once daily for up to 28 days
Arm Title
SOC plus Placebo
Arm Type
Placebo Comparator
Arm Description
SOC plus intravenous placebo every 8 hours for 6 doses followed by once daily for up to 28 days
Intervention Type
Drug
Intervention Name(s)
Isavuconazonium Injection [Cresemba]
Other Intervention Name(s)
Isavuconazole, Cresemba
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous placebo every 8 hours for 6 doses followed by intravenous placebo once daily for up to 28 days
Primary Outcome Measure Information:
Title
The incidence of SARS-CoV-2-associated invasive aspergillosis at time of ICU discharge
Description
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
Secondary Outcome Measure Information:
Title
The incidence of SARS-CoV-2-associated non-Aspergillus invasive fungal infections at time of ICU discharge
Description
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
Title
Survival
Description
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
Title
Length of ICU stay
Description
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
Title
Length of Hospital stay
Description
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
Title
Mortality
Description
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
Title
Adverse events
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Jenks, MD, MPH
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
George Thompson, MD
Organizational Affiliation
University of California, Davis
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Martin Hoenigl, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Study Chair
Facility Information:
Facility Name
University of California Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Isavuconazole for the Prevention of COVID-19-associated Pulmonary Aspergillosis

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