Background: Invasive fungal diseases (IFD) caused by dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISA) is a novel, broad-spectrum, triazole antifungal agent (IV and PO) being developed for treatment of IFD. It displays potent activity in vitro against dimorphic fungi. We report outcomes in a subset of patients enrolled in the VITAL trial with IFD caused by these pathogens.
Methods: VITAL (NCT00634049) was an open-label Phase 3 trial conducted to evaluate efficacy and safety of ISA treatment in rare IFD. Patients received ISA 200 mg TID for 2 days followed by 200 mg QD (IV or PO). Proven/ probable IFD (EORTC/MSG criteria) and overall response at end-of-treatment (EOT) were determined by an independent, data-review committee (DRC). Mortality and safety were also analyzed.
Results: Twenty-nine patients received ISA for IFD caused by dimorphic fungi. Isolated pathogens were Paracoccidioides spp. (n=10), Coccidioides spp. (n=9), Histoplasma spp. (n=7), and Blastomyces spp. (n=3). CLSI MIC data were available for 9 isolates: Paracoccidioides, <0.001 mg/L (n=1); Coccidioides, 0.06–0.12 mg/L (n=6), and Histoplasma, 0.03 mg/L (n=2). Twenty-five patients had pulmonary involvement and 13 had disseminated disease. Treatment duration ranged from 2–331 days and was ≥175 days in 24 patients. Twenty-six patients were alive ≥100 days after starting ISA therapy; 18 of whom were overall successes, as assessed by the DRC. Three patients died: 1 on Day 20 (Blastomyces), and 2 on Days 27 and 91 (Paracoccidioides); all were considered treatment failures (progression). Adverse events (AEs) and drug-related AEs were reported in 86.2% and 37.9% of patients, respectively.
Conclusions: Successful outcomes were observed in patients treated with ISA with IFD caused by dimorphic fungi, which supports further investigation of ISA therapy for these infections. ClinicalTrials.gov Identifier: NCT00634049
- ICAAC 54th (2014)