Objectives: Isavuconazole is a water-soluble, broad-spectrum triazole antifungal developed for the treatment of invasive fungal disease (IFD). We present outcomes, safety, and tolerability of isavuconazole-treated patients from the Phase 3 VITAL trial (NCT00634049). Methods: VITAL evaluated safety and efficacy of open-label isavuconazole treatment of invasive aspergillosis in patients with renal impairment, and in patients with IFD caused by Mucorales, other emerging moulds, yeasts, and dimorphic fungi. Patients received isavuconazole 200mg (IV/PO) TID for 2 days, then 200mg QD (IV/PO) to end of treatment (EOT; ≤180 days). The key outcome measure was all-cause mortality (ACM) through Day 42 in all isavuconazole-treated patients. Treatment-emergent adverse events (TEAEs) were monitored and assessed throughout the trial. Results: A total of 149 patients were enrolled, of whom 146 were treated with isavuconazole. Most patients were male (68.5%), White (74.0%), and received isavuconazole as primary therapy (65.0%; defined as ≤4 days of any other systemic antifungal treatment). Pathogens confirmed by an independent data-review committee included Mucorales (26.6%), dimorphic fungi (20.3%), Aspergillus species (14.7%), other filamentous fungi (11.9%), mixed infections (10.5%), non-Candida yeasts (7.7%), and other moulds (4.9%). Patients’ clinical characteristics, outcomes, and safety are shown in Table A. ACM through Day 42 was 12.5% and 37.8% among patients with invasive aspergillosis and mucormycosis, respectively. The most common TEAEs and drug-related TEAEs were vomiting (24.7% and 7.5%, respectively) and nausea (23.3% and 6.2%, respectively). In total, 11.0% of patients experienced hepatobiliary disorders and 13.0% experienced eye disorders. Increased serum creatinine was observed in some patients: ≥50% increase (12.1%) and ≥100% increase (5.0%) from baseline. Very few patients experienced hepatotoxicity: 1.4% alanine transaminase and 2.2% aspartate transaminase >3x upper limit of normal at EOT. Conclusion: Isavuconazole was safe and well tolerated in this high-risk, immunocompromised population of patients with IFD.
Table A. Clinical characteristics, outcomes, and safety.
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- ISHAM 19th (2015)