title: Randomized trial of micafungin for the prevention of invasive fungal infection in high-risk liver transplant recipients.
abstract: BACKGROUND
  Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk.
  
  
  METHODS
  In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests.
  
  
  RESULTS
  The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for micafungin and 99.3% for standard care (Δ standard care - micafungin [95% confidence interval], 0.7% [-2.7% to 4.4%]) in the per protocol set and 96.5% and 93.6%, respectively (-2.9% [-8.0% to 1.9%]), in the full analysis set. Incidences of drug-related adverse events for micafungin and standard care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. At EOP, liver function tests were similar but creatinine clearance was higher in micafungin- vs standard care-treated patients.
  
  
  CONCLUSIONS
  Micafungin was noninferior to standard care as antifungal prophylaxis in liver transplant patients at high risk for IFI. Adverse event profiles and liver function at EOP were similar, although kidney function was better with micafungin.
  
  
  BACKGROUND
  NCT01058174.
authors.affiliation: Hôpital Paul Brousse, Villejuif, France.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.affiliation: Charite Universitätsmedizin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.affiliation: Hôpital de Rangueil, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cointault
authors.affiliation: St Luc University Hospital, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.affiliation: Hospital Clinic i Provincial, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cervera
authors.affiliation: Ghent University Hospital, Belgium.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
authors.affiliation: Azienda Ospedaliera di Padova, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
authors.affiliation: Semmelweis University, Budapest, Hungary.
authors.forename: Róbert M
authors.initials: RM
authors.lastname: Langer
authors.affiliation: Azienda Ospedaliero Universitaria Misericordia, Udine, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Lugano
authors.affiliation: Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Göran-Ericzon
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: Stephen
authors.initials: S
authors.lastname: Phillips
authors.affiliation: Astellas Pharma Europe Medical Affairs, Chertsey, United Kingdom.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Tweddle
authors.affiliation: Astellas Pharma Europe Medical Affairs, Chertsey, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Karas
authors.affiliation: Astellas Pharma Global Medical Affairs, Northbrook, Illinois.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Brown
authors.affiliation: University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D054714:Echinocandins / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D055666:Lipopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D066027:Transplant Recipients; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
keywords: antifungal therapy; infection; liver transplant; micafungin; prophylaxis