1.
ssrn; 2024.
Preprint
in English
| PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4698359
2.
ClinicalTrials.gov; 08/01/2021; TrialID: NCT04707703
Clinical Trial Register
| ICTRP | ID: ictrp-NCT04707703
ABSTRACT
Condition:
Severe Acute Respiratory Syndrome Coronavirus 2;Aspergillosis InvasiveIntervention:
Drug: Isavuconazonium Injection [Cresemba];Drug: PlaceboPrimary outcome:
The incidence of SARS-CoV-2-associated invasive aspergillosis at time of ICU dischargeCriteria:
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.