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

NCT04707703 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: 200639
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

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).

Conditions

Severe Acute Respiratory Syndrome Coronavirus 2; Aspergillosis Invasive

Keywords

Isavuconazole; Antifungal Agents; Anti-infective Agents; Coronavirus-associated Invasive Pulmonary Aspergillosis; CAPA

Outcome Measures

Primary Outcomes (1)

• 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

  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

  From date of admission in ICU assessed up to ICU discharge, approximately 28 days

• Survival

  From date of admission in ICU assessed up to ICU discharge, approximately 28 days

• Length of ICU stay

  From date of admission in ICU assessed up to ICU discharge, approximately 28 days

• Length of Hospital stay

  From date of admission in ICU assessed up to hospital discharge, approximately 32 days

• Mortality

  At 30 and 90 days

Study Arms (2)

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

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

Drug: Placebo

Interventions

Isavuconazonium Injection [Cresemba] DRUG

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

Also known as: Isavuconazole, Cresemba

SOC plus Isavuconazonium sulfate

Placebo DRUG

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

SOC plus Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jeffrey Jenks, MD, MPH: lead
• Astellas Pharma Global Development, Inc.: collaborator

Study Sites (3)

University of California Irvine

Orange, California, 92868, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Related Publications (1)

• 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.

  PMID: 38419156 DERIVED

MeSH Terms

Interventions

isavuconazole

Study Officials

• Jeffrey Jenks, MD, MPH

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• George Thompson, MD

  University of California, Davis

  STUDY CHAIR

• Martin Hoenigl, MD

  University of California, San Diego

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assoc Physician

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 13, 2021
• Study Start: March 16, 2021
• Primary Completion: October 25, 2021
• Study Completion: October 25, 2021
• Last Updated: November 25, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)