Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis

• Autoři: MARTY Francisco M; OSTROSKY-ZEICHNER Luis; CORNELY Oliver A; MULLANE Kathleen M; PERFECT John R; THOMPSON III George R; ALANGADEN George J; BROWN Janice M; FREDRICKS David N; HEINZ Werner J; HERBRECHT Raoul; KLIMKO Nikolai; KLYASOVA Galina; MAERTENS Johan A; MELINKERI Sameer R; OREN Ilana; PAPPAS Peter G; RÁČIL Zdeněk; RAHAV Galia; SANTOS Rodrigo; SCHWARTZ Stefan; VEHRESCHILD J Janne; YOUNG Jo-Anne H; CHETCHOTISAKD Ploenchan; JARURATANASIRIKUL Sutep; KANJ Souha S; ENGELHARDT Marc; KAUFHOLD Achim; ITO Masanori; LEE Misun; SASSE Carolyn; MAHER Rochelle M; ZEIHER Bernhardt; VEHRESCHILD Maria J G T
• Rok publikování: 2016
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Lancet Infectious Diseases
• Fakulta / Pracoviště MU: Lékařská fakulta
• Doi: http://dx.doi.org/10.1016/S1473-3099(16)00071-2
• Obor: Epidemiologie, infekční nemoci a klinická imunologie
• Klíčová slova: LIPOSOMAL AMPHOTERICIN-B; MYCOSES STUDY-GROUP; FUNGAL-INFECTIONS; INVASIVE ASPERGILLOSIS; TRANSPLANT RECIPIENTS; EUROPEAN-ORGANIZATION; SALVAGE THERAPY; ZYGOMYCOSIS; POSACONAZOLE; VORICONAZOLE
• Popis: Background Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the effi cacy and safety of isavuconazole for treatment of mucormycosis and compared its effi cacy with amphotericin B in a matched case-control analysis. Methods In a single-arm open-label trial (VITAL study), adult patients (>= 18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response—ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)—according to prespecifi ed criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 allcause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Findings Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19–179, range 2–882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). Interpretation Isavuconazole showed activity against mucormycosis with effi cacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated.