Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial.
BACKGROUND
Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare micafungin with liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidosis.


METHODS
We did a double-blind, randomised, multinational non-inferiority study to compare micafungin (100 mg/day) with liposomal amphotericin B (3 mg/kg per day) as first-line treatment of candidaemia and invasive candidosis. The primary endpoint was treatment success, defined as both a clinical and a mycological response at the end of treatment. Primary analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT00106288.


RESULTS
264 individuals were randomly assigned to treatment with micafungin; 267 were randomly assigned to receive liposomal amphotericin B. 202 individuals in the micafungin group and 190 in the liposomal amphotericin B group were included in the per-protocol analyses. Treatment success was observed for 181 (89.6%) patients treated with micafungin and 170 (89.5%) patients treated with liposomal amphotericin B. The difference in proportions, after stratification by neutropenic status at baseline, was 0.7% (95% CI -5.3 to 6.7). Efficacy was independent of the Candida spp and primary site of infection, as well as neutropenic status, APACHE II score, and whether a catheter was removed or replaced during the study. There were fewer treatment-related adverse events--including those that were serious or led to treatment discontinuation--with micafungin than there were with liposomal amphotericin B.


CONCLUSIONS
Micafungin was as effective as--and caused fewer adverse events than--liposomal amphotericin B as first-line treatment of candidaemia and invasive candidosis.
Kuse
Ernst-Rüdiger
ER
Klinik für Viszeral und Transplantationschirurgie, Hannover, Germany.
Chetchotisakd
Ploenchan
P
Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand.
da Cunha
Clovis Arns
CA
R Desembargador Vieira Cavalcante, Curitiba, Brazil.
Ruhnke
Markus
M
Charité-Universitätsmedizin Berlin, Berlin, Germany.
Barrios
Carlos
C
Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil.
Raghunadharao
Digumarti
D
Nizam's Institute of Medical Sciences, Hyderabad, India.
Sekhon
Jagdev Singh
JS
Dayanand Medical College and Hospital, Ludhiana, India.
Freire
Antonio
A
Santa Casa de Misericordia de Belo Horizonte Santa Efigenia, Belo Horizonte, Brazil.
Ramasubramanian
Venkatasubramanian
V
Apollo Hospitals, Chennai, India.
Demeyer
Ignace
I
OLV Ziekenhuis Aalst, Aalst, Belgium.
Nucci
Marcio
M
Hospital Universitario Clementino Fraga Filko UFRJ, Rio de Janeiro, Brazil.
Leelarasamee
Amorn
A
Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Jacobs
Frédérique
F
Hopital Erasme - ULB, Brussels, Belgium.
Decruyenaere
Johan
J
UZ Gent, Gent, Belgium.
Pittet
Didier
D
University of Geneva Hospitals, Geneva, Switzerland.
Ullmann
Andrew J
AJ
Klinikum der Johannes-Gutenberg-Universität, Mainz, Germany.
Ostrosky-Zeichner
Luis
L
University of Texas Medical School, Houston, TX, USA.
Lortholary
Olivier
O
U Paris V, Hôpital Necker-Enfants Malades and Institut Pasteur, Paris, France.
Koblinger
Sonja
S
Astellas Pharma GmbH, Munich, Germany.
Diekmann-Berndt
Heike
H
Astellas Pharma GmbH, Munich, Germany.
Cornely
Oliver A
OA
Universitätsklinik Köln, Klinik I für Innere Medizin, Köln, Germany. Electronic address: Oliver.Cornely@ctuc.de.
D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D054714:Echinocandins; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use*; D008297:Male; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D016896:Treatment Outcome
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077551:Micafungin