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

被引：538

作者：

Marty, Francisco M. ^{[1
]}

Ostrosky-Zeichner, Luis ^{[2
,3
]}

Cornely, Oliver A. ^{[4
]}

Mullane, Kathleen M. ^{[5
,6
]}

Perfect, John R. ^{[7
,8
]}

Thompson, George R., III ^{[9
,10
]}

Alangaden, George J. ^{[11
]}

Brown, Janice M. ^{[12
]}

Fredricks, David N. ^{[13
]}

Heinz, Werner J. ^{[14
]}

Herbrecht, Raoul ^{[15
]}

Klimko, Nikolai ^{[16
]}

Klyasova, Galina ^{[17
]}

Maertens, Johan A. ^{[18
]}

Melinkeri, Sameer R. ^{[19
]}

Oren, Ilana ^{[20
]}

Pappas, Peter G. ^{[21
]}

Racil, Zdenek ^{[22
,23
]}

Rahav, Galia ^{[24
]}

Santos, Rodrigo ^{[25
]}

Schwartz, Stefan ^{[26
]}

Vehreschild, J. Janne ^{[27
,28
]}

Young, Jo-Anne H. ^{[29
,30
]}

Chetchotisakd, Ploenchan ^{[31
]}

Jaruratanasirikul, Sutep ^{[32
]}

Kanj, Souha S. ^{[33
]}

Engelhardt, Marc ^{[34
]}

Kaufh, Achim ^{[34
]}

Ito, Masanori ^{[35
]}

Lee, Misun ^{[35
]}

Sasse, Carolyn ^{[35
]}

Maher, Rochelle M. ^{[35
]}

Zeiher, Bernhardt ^{[35
]}

Vehreschild, Maria J. G. T. ^{[27
,28
]}

机构：

[1] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA

[2] Univ Texas Houston, Sch Med, Houston, TX USA

[3] Univ Texas Houston, Mem Hermann Texas Med Ctr, Houston, TX USA

[4] Univ Cologne, ZKS Koln, Cologne Excellence Cluster Cellular Stress Respon, Clin Trials Ctr Cologne,Dept Internal Med, D-50924 Cologne, Germany

[5] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

[6] Univ Chicago, Div Infect Dis, 5841 S Maryland Ave, Chicago, IL 60637 USA

[7] Duke Univ, Dept Med, Durham, NC USA

[8] Duke Univ, Div Infect Dis, Durham, NC USA

[9] Univ Calif Davis, Dept Med, Davis, CA 95616 USA

[10] Univ Calif Davis, Div Infect Dis & Med Microbiol & Immunol, Davis, CA 95616 USA

[11] Henry Ford Hosp, Dept Internal Med, Div Infect Dis, Detroit, MI 48202 USA

[12] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA

[13] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[14] Univ Wurzburg, Med Ctr, D-97070 Wurzburg, Germany

[15] Univ Strasbourg, Hautepierre Hosp, Dept Hematol & Oncol, Strasbourg, France

[16] North Western State Med Univ, St Petersburg, Russia

[17] Natl Res Ctr Hematol, Moscow, Russia

[18] Univ Hosp Gasthuisberg, Dept Hematol, Leuven, Belgium

[19] Deenanath Mangeshkar Hosp & Res Ctr, Pune, Maharashtra, India

[20] Rambam Hlth Care Campus, Infect Dis Unit, Haifa, Israel

[21] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL USA

[22] Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic

[23] Masaryk Univ, Fac Med, Brno, Czech Republic

[24] Sheba Med Ctr, Infect Dis Unit, Tel Hashomer, Israel

[25] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil

[26] Charite, Med Klin 3, Campus Benjamin Franklin, Berlin, Germany

[27] Univ Hosp Cologne, Dept Internal Med, Cologne, Germany

[28] German Ctr Infect Res, Partner Site Bonn Cologne, Cologne, Germany

[29] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA

[30] Univ Minnesota, Div Infect Dis, Box 736 UMHC, Minneapolis, MN 55455 USA

[31] Khon Kaen Univ, Srinagarind Hosp, Div Infect Dis & Trop Med, Khon Kaen, Thailand

[32] Prince Songkla Univ, Songklanagarind Hosp, Dept Med, Hat Yai, Thailand

[33] Amer Univ Beirut, Med Ctr, Dept Internal Med, Beirut, Lebanon

[34] Basilea Pharmaceut Int, Basel, Switzerland

[35] Astellas Pharma Global Dev, Northbrook, IL USA

来源：

LANCET INFECTIOUS DISEASES | 2016年 / 16卷 / 07期

关键词：

LIPOSOMAL AMPHOTERICIN-B; MYCOSES STUDY-GROUP; FUNGAL-INFECTIONS; INVASIVE ASPERGILLOSIS; TRANSPLANT RECIPIENTS; EUROPEAN-ORGANIZATION; SALVAGE THERAPY; ZYGOMYCOSIS; POSACONAZOLE; VORICONAZOLE;

D O I：

10.1016/S1473-3099(16)00071-2

中图分类号：

R51 [传染病];

学科分类号：

100201 [内科学];

摘要：

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 efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy 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 prespecified 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 all-cause 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 efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated.

引用

页码：828 / 837

页数：10

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