Severe Acute Respiratory Syndrome Coronavirus 2Phase 3Isavu-CAPANCT04707703
Isavuconazole for the Prevention of COVID-19-associated Pulmonary Aspergillosis
A Phase 3 study testing Isavuconazonium Injection [Cresemba] in people with Severe Acute Respiratory Syndrome Coronavirus 2 and Aspergillosis Invasive, run by Jeffrey Jenks, MD, MPH at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Acute Respiratory Syndrome Coronavirus 2, Aspergillosis Invasive
- What is being tested?
- Isavuconazonium Injection [Cresemba]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- 16 Mar 2021to 25 Oct 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of California Irvine
Orange, California, 92868
University of California Davis
Sacramento, California, 95817
University of California San Diego
San Diego, California, 92103
About this study
Official title: 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).
Read the 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).
- Being tested
- Isavuconazonium Injection [Cresemba], Placebo
- Keywords
- Isavuconazole, Antifungal Agents, Anti-infective Agents, Coronavirus-associated Invasive Pulmonary Aspergillosis, CAPA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isavuconazonium Injection [Cresemba]Drug
Also called Isavuconazole, 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
PlaceboDrug
Intravenous placebo every 8 hours for 6 doses followed by intravenous placebo once daily for up to 28 days
| Study group | Role | What they receive |
|---|---|---|
| SOC plus Isavuconazonium sulfate | Experimental | SOC plus intravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by 372mg once daily for up to 28 days Receives: Drug: Isavuconazonium Injection [Cresemba] |
| SOC plus Placebo | Placebo comparator | SOC plus intravenous placebo every 8 hours for 6 doses followed by once daily for up to 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From date of admission in ICU assessed up to ICU discharge, approximately 28 days
Secondary outcomes (6)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: At 30 and 90 days
Adverse events
Compare the rates of adverse events in those who receive isavuconazole compared to those who receive placebo
Measured: From date of start of isavuconazole or placebo through duration of isavuconazole or placebo, approximately 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2021
- Study start16 Mar 2021
- Primary completion25 Oct 2021
- Study completion25 Oct 2021
Why it stopped: Participant enrollment challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Acute Respiratory Syndrome Coronavirus 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Jenks, MD, MPH
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Global Development, Inc.
- Responsible party
- Sponsor-investigator, Jeffrey Jenks, MD, MPH, University of California, San Diego
- Investigators
- Jeffrey Jenks, MD, MPH, Principal investigator, University of California, San DiegoGeorge Thompson, MD, Study chair, University of California, DavisMartin Hoenigl, MD, Study chair, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04707703
- Sponsor's protocol ID
- 200639
- Acronym
- Isavu-CAPA
- Status last verified
- Jul 2022
- First submitted
- 8 Jan 2021
- Last updated
- 25 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Permpalung N, Chiang TP, Manothummetha K, Ostrander D, Datta K, Segev DL, Durand CM, Mostafa HH, Zhang SX, Massie AB, Marr KA, Avery RK. Invasive Fungal Infections in Inpatient Solid Organ Transplant Recipients With COVID-19: A Multicenter Retrospective Cohort. Transplantation. 2024 Jul 1;108(7):1613-1622. doi: 10.1097/TP.0000000000004947. Epub 2024 Jun 20.
PubMed 38419156
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Isavuconazole for the Prevention of SARS-CoV-2-associated Invasive Aspergillosis in Critically-Ill Patients
- ClinicalTrials.gov ID
- NCT04707703
- Acronym / sponsor ID
- Isavu-CAPA / 200639
- Keywords
- Isavuconazole, Antifungal Agents, Anti-infective Agents, Coronavirus-associated Invasive Pulmonary Aspergillosis, CAPA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Participant enrollment challenges
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Jeffrey Jenks, MD, MPHUniversity, hospital or other
- Collaborators
- Astellas Pharma Global Development, Inc.
- Study start
- 16 Mar 2021 (actual)
- Primary completion
- 25 Oct 2021 (actual)
- Study completion
- 25 Oct 2021 (actual)
- First posted
- 13 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOC plus Isavuconazonium sulfate | Experimental | Drug: Isavuconazonium Injection [Cresemba]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 Placebo | Placebo comparator | Drug: PlaceboSOC plus intravenous placebo every 8 hours for 6 doses followed by once daily for up to 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isavuconazonium Injection [Cresemba]Also: Isavuconazole, CresembaIntravenous isavuconazonium sulfate 372 mg every 8 hours for 6 doses followed by intravenous isavuconazonium sulfate 372 mg once daily for up to 28 days | Drug | SOC plus Isavuconazonium sulfate |
| PlaceboIntravenous placebo every 8 hours for 6 doses followed by intravenous placebo once daily for up to 28 days | Drug | SOC plus Placebo |
Primary outcome
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
6 secondary outcomes
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
Survival
Time frame: 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
Length of Hospital stay
Time frame: From date of admission in ICU assessed up to hospital discharge, approximately 32 days
Mortality
Time frame: 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
Results and safety
The study was stopped early (reason given: Participant enrollment challenges). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2022.
- Derived from this study: PubMed 38419156Permpalung N, Chiang TP, Manothummetha K, Ostrander D, Datta K, Segev DL, Durand CM, Mostafa HH, Zhang SX, Massie AB, Marr KA, Avery RK. Invasive Fungal Infections in Inpatient Solid Organ Transplant Recipients With COVID-19: A Multicenter Retrospective Cohort. Transplantation. 2024 Jul 1;108(7):1613-1622. doi: 10.1097/TP.0000000000004947. Epub 2024 Jun 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Jenks, MD, MPH principal investigator
University of California, San Diego
George Thompson, MD study chair
University of California, Davis
Martin Hoenigl, MD study chair
University of California, San Diego
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Isavuconazonium Injection [Cresemba] in people with Severe Acute Respiratory Syndrome Coronavirus 2 and Aspergillosis Invasive, run by Jeffrey Jenks, MD, MPH at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Participant enrollment challenges). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04707703, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2022.