A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

Jan Pachl; Petr Svoboda; Frédérique Jacobs; Koenraad Vandewoude; Ben van der Hoven; Peter Spronk; Gary Masterson; Manu Malbrain; Mickael Aoun; Jorge Garbino; Jukka Takala; Lubos Drgona; James Burnie; Ruth Matthews; Mycograb Invasive Candidiasis Study Group

doi:10.1086/503428

A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

Jan Pachl, Petr Svoboda, Frédérique Jacobs, Koenraad Vandewoude, Ben van der Hoven, Peter Spronk, Gary Masterson, Manu Malbrain, Mickael Aoun, Jorge Garbino, Jukka Takala, Lubos Drgona, James Burnie, Ruth Matthews, Mycograb Invasive Candidiasis Study Group

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290 Citations (Scopus)

Abstract

BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.

METHODS: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.

RESULTS: Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.

CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

Original language	English
Pages (from-to)	1404-1413
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	42
Issue number	10
DOIs	https://doi.org/10.1086/503428
Publication status	Published - 2006

Keywords

Adult
Aged
Amphotericin B
Antibodies, Monoclonal
Antifungal Agents
Candida
Candidiasis
Double-Blind Method
Female
HSP90 Heat-Shock Proteins
Humans
Male
Middle Aged
Patient Selection
Placebos
Recombinant Proteins
Treatment Outcome
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

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Pachl, J., Svoboda, P., Jacobs, F., Vandewoude, K., van der Hoven, B., Spronk, P., Masterson, G., Malbrain, M., Aoun, M., Garbino, J., Takala, J., Drgona, L., Burnie, J., Matthews, R., & Mycograb Invasive Candidiasis Study Group (2006). A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clinical Infectious Diseases, 42(10), 1404-1413. https://doi.org/10.1086/503428

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title = "A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis",

abstract = "BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.METHODS: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.RESULTS: Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.",

keywords = "Adult, Aged, Amphotericin B, Antibodies, Monoclonal, Antifungal Agents, Candida, Candidiasis, Double-Blind Method, Female, HSP90 Heat-Shock Proteins, Humans, Male, Middle Aged, Patient Selection, Placebos, Recombinant Proteins, Treatment Outcome, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",

author = "Jan Pachl and Petr Svoboda and Fr{\'e}d{\'e}rique Jacobs and Koenraad Vandewoude and {van der Hoven}, Ben and Peter Spronk and Gary Masterson and Manu Malbrain and Mickael Aoun and Jorge Garbino and Jukka Takala and Lubos Drgona and James Burnie and Ruth Matthews and {Mycograb Invasive Candidiasis Study Group}",

year = "2006",

doi = "10.1086/503428",

language = "English",

volume = "42",

pages = "1404--1413",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "10",

}

Pachl, J, Svoboda, P, Jacobs, F, Vandewoude, K, van der Hoven, B, Spronk, P, Masterson, G, Malbrain, M, Aoun, M, Garbino, J, Takala, J, Drgona, L, Burnie, J, Matthews, R & Mycograb Invasive Candidiasis Study Group 2006, 'A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis', Clinical Infectious Diseases, vol. 42, no. 10, pp. 1404-1413. https://doi.org/10.1086/503428

A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. / Pachl, Jan; Svoboda, Petr; Jacobs, Frédérique et al.
In: Clinical Infectious Diseases, Vol. 42, No. 10, 2006, p. 1404-1413.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

AU - Pachl, Jan

AU - Svoboda, Petr

AU - Jacobs, Frédérique

AU - Vandewoude, Koenraad

AU - van der Hoven, Ben

AU - Spronk, Peter

AU - Masterson, Gary

AU - Malbrain, Manu

AU - Aoun, Mickael

AU - Garbino, Jorge

AU - Takala, Jukka

AU - Drgona, Lubos

AU - Burnie, James

AU - Matthews, Ruth

AU - Mycograb Invasive Candidiasis Study Group

PY - 2006

Y1 - 2006

N2 - BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.METHODS: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.RESULTS: Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

AB - BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.METHODS: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.RESULTS: Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

KW - Adult

KW - Aged

KW - Amphotericin B

KW - Antibodies, Monoclonal

KW - Antifungal Agents

KW - Candida

KW - Candidiasis

KW - Double-Blind Method

KW - Female

KW - HSP90 Heat-Shock Proteins

KW - Humans

KW - Male

KW - Middle Aged

KW - Patient Selection

KW - Placebos

KW - Recombinant Proteins

KW - Treatment Outcome

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1086/503428

DO - 10.1086/503428

M3 - Article

C2 - 16619152

SN - 1058-4838

VL - 42

SP - 1404

EP - 1413

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 10

ER -

A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

Abstract

Keywords

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