title: Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial.
abstract: 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.
authors.affiliation: Klinik für Viszeral und Transplantationschirurgie, Hannover, Germany.
authors.forename: Ernst-Rüdiger
authors.initials: ER
authors.lastname: Kuse
authors.affiliation: Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
authors.affiliation: R Desembargador Vieira Cavalcante, Curitiba, Brazil.
authors.forename: Clovis Arns
authors.initials: CA
authors.lastname: da Cunha
authors.affiliation: Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ruhnke
authors.affiliation: Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Barrios
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Digumarti
authors.initials: D
authors.lastname: Raghunadharao
authors.affiliation: Dayanand Medical College and Hospital, Ludhiana, India.
authors.forename: Jagdev Singh
authors.initials: JS
authors.lastname: Sekhon
authors.affiliation: Santa Casa de Misericordia de Belo Horizonte Santa Efigenia, Belo Horizonte, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Freire
authors.affiliation: Apollo Hospitals, Chennai, India.
authors.forename: Venkatasubramanian
authors.initials: V
authors.lastname: Ramasubramanian
authors.affiliation: OLV Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Demeyer
authors.affiliation: Hospital Universitario Clementino Fraga Filko UFRJ, Rio de Janeiro, Brazil.
authors.forename: Marcio
authors.initials: M
authors.lastname: Nucci
authors.affiliation: Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Amorn
authors.initials: A
authors.lastname: Leelarasamee
authors.affiliation: Hopital Erasme - ULB, Brussels, Belgium.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.affiliation: UZ Gent, Gent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Decruyenaere
authors.affiliation: University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Pittet
authors.affiliation: Klinikum der Johannes-Gutenberg-Universität, Mainz, Germany.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.affiliation: University of Texas Medical School, Houston, TX, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.affiliation: U Paris V, Hôpital Necker-Enfants Malades and Institut Pasteur, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Astellas Pharma GmbH, Munich, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Koblinger
authors.affiliation: Astellas Pharma GmbH, Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Diekmann-Berndt
authors.affiliation: Universitätsklinik Köln, Klinik I für Innere Medizin, Köln, Germany. Electronic address: Oliver.Cornely@ctuc.de.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077551:Micafungin