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

J 2016

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

MARTY, Francisco M, Luis OSTROSKY-ZEICHNER, Oliver A CORNELY, Kathleen M MULLANE, John R PERFECT et. al.

Basic information

Original name

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

Authors

MARTY, Francisco M (840 United States of America), Luis OSTROSKY-ZEICHNER (840 United States of America), Oliver A CORNELY (276 Germany), Kathleen M MULLANE (840 United States of America), John R PERFECT (840 United States of America), George R THOMPSON III (840 United States of America), George J ALANGADEN (840 United States of America), Janice M BROWN (840 United States of America), David N FREDRICKS (840 United States of America), Werner J HEINZ (276 Germany), Raoul HERBRECHT (250 France), Nikolai KLIMKO (643 Russian Federation), Galina KLYASOVA (643 Russian Federation), Johan A MAERTENS (56 Belgium), Sameer R MELINKERI (356 India), Ilana OREN (376 Israel), Peter G PAPPAS (840 United States of America), Zdeněk RÁČIL (203 Czech Republic, guarantor, belonging to the institution), Galia RAHAV (376 Israel), Rodrigo SANTOS (76 Brazil), Stefan SCHWARTZ (276 Germany), J Janne VEHRESCHILD (276 Germany), Jo-Anne H YOUNG (840 United States of America), Ploenchan CHETCHOTISAKD (764 Thailand), Sutep JARURATANASIRIKUL (764 Thailand), Souha S KANJ (422 Lebanon), Marc ENGELHARDT (756 Switzerland), Achim KAUFHOLD (756 Switzerland), Masanori ITO (840 United States of America), Misun LEE (840 United States of America), Carolyn SASSE (840 United States of America), Rochelle M MAHER (840 United States of America), Bernhardt ZEIHER (840 United States of America) and Maria J G T VEHRESCHILD (276 Germany)

Edition

Lancet Infectious Diseases, Oxford, Elsevier SCI LTD, 2016, 1473-3099

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30300 3.3 Health sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 19.864

RIV identification code

RIV/00216224:14110/16:00089550

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/S1473-3099(16)00071-2

UT WoS

000378319600039

Keywords in English

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

Abstract

V originále

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.

Citovat

MARTY, Francisco M, Luis OSTROSKY-ZEICHNER, Oliver A CORNELY, Kathleen M MULLANE, John R PERFECT, George R THOMPSON III, George J ALANGADEN, Janice M BROWN, David N FREDRICKS, Werner J HEINZ, Raoul HERBRECHT, Nikolai KLIMKO, Galina KLYASOVA, Johan A MAERTENS, Sameer R MELINKERI, Ilana OREN, Peter G PAPPAS, Zdeněk RÁČIL, Galia RAHAV, Rodrigo SANTOS, Stefan SCHWARTZ, J Janne VEHRESCHILD, Jo-Anne H YOUNG, Ploenchan CHETCHOTISAKD, Sutep JARURATANASIRIKUL, Souha S KANJ, Marc ENGELHARDT, Achim KAUFHOLD, Masanori ITO, Misun LEE, Carolyn SASSE, Rochelle M MAHER, Bernhardt ZEIHER and Maria J G T VEHRESCHILD. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infectious Diseases. Oxford: Elsevier SCI LTD, 2016, vol. 16, No 7, p. 828-837. ISSN 1473-3099. Available from: https://dx.doi.org/10.1016/S1473-3099(16)00071-2.

@article{1339539,
   author = {Marty, Francisco M and OstroskyandZeichner, Luis and Cornely, Oliver A and Mullane, Kathleen M and Perfect, John R and Thompson III, George R and Alangaden, George J and Brown, Janice M and Fredricks, David N and Heinz, Werner J and Herbrecht, Raoul and Klimko, Nikolai and Klyasova, Galina and Maertens, Johan A and Melinkeri, Sameer R and Oren, Ilana and Pappas, Peter G and Ráčil, Zdeněk and Rahav, Galia and Santos, Rodrigo and Schwartz, Stefan and Vehreschild, J Janne and Young, JoandAnne H and Chetchotisakd, Ploenchan and Jaruratanasirikul, Sutep and Kanj, Souha S and Engelhardt, Marc and Kaufhold, Achim and Ito, Masanori and Lee, Misun and Sasse, Carolyn and Maher, Rochelle M and Zeiher, Bernhardt and Vehreschild, Maria J G T},
   article_location = {Oxford},
   article_number = {7},
   doi = {http://dx.doi.org/10.1016/S1473-3099(16)00071-2},
   keywords = {LIPOSOMAL AMPHOTERICIN-B; MYCOSES STUDY-GROUP; FUNGAL-INFECTIONS; INVASIVE ASPERGILLOSIS; TRANSPLANT RECIPIENTS; EUROPEAN-ORGANIZATION; SALVAGE THERAPY; ZYGOMYCOSIS; POSACONAZOLE; VORICONAZOLE},
   language = {eng},
   issn = {1473-3099},
   journal = {Lancet Infectious Diseases},
   title = {Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis},
   volume = {16},
   year = {2016}
}

TY  - JOUR
ID  - 1339539
AU  - 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
PY  - 2016
TI  - Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis
JF  - Lancet Infectious Diseases
VL  - 16
IS  - 7
SP  - 828-837
EP  - 828-837
PB  - Elsevier SCI LTD
SN  - 14733099
KW  - LIPOSOMAL AMPHOTERICIN-B
KW  - MYCOSES STUDY-GROUP
KW  - FUNGAL-INFECTIONS
KW  - INVASIVE ASPERGILLOSIS
KW  - TRANSPLANT RECIPIENTS
KW  - EUROPEAN-ORGANIZATION
KW  - SALVAGE THERAPY
KW  - ZYGOMYCOSIS
KW  - POSACONAZOLE
KW  - VORICONAZOLE
N2  - 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.
ER  -

MARTY, Francisco M, Luis OSTROSKY-ZEICHNER, Oliver A CORNELY, Kathleen M MULLANE, John R PERFECT, George R THOMPSON III, George J ALANGADEN, Janice M BROWN, David N FREDRICKS, Werner J HEINZ, Raoul HERBRECHT, Nikolai KLIMKO, Galina KLYASOVA, Johan A MAERTENS, Sameer R MELINKERI, Ilana OREN, Peter G PAPPAS, Zdeněk RÁČIL, Galia RAHAV, Rodrigo SANTOS, Stefan SCHWARTZ, J Janne VEHRESCHILD, Jo-Anne H YOUNG, Ploenchan CHETCHOTISAKD, Sutep JARURATANASIRIKUL, Souha S KANJ, Marc ENGELHARDT, Achim KAUFHOLD, Masanori ITO, Misun LEE, Carolyn SASSE, Rochelle M MAHER, Bernhardt ZEIHER and Maria J G T VEHRESCHILD. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. \textit{Lancet Infectious Diseases}. Oxford: Elsevier SCI LTD, 2016, vol.~16, No~7, p.~828-837. ISSN~1473-3099. Available from: https://dx.doi.org/10.1016/S1473-3099(16)00071-2.

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