Randomized trial of micafungin for the prevention of invasive fungal infection in high-risk liver transplant recipients

Clin Infect Dis. 2015 Apr 1;60(7):997-1006. doi: 10.1093/cid/ciu1128. Epub 2014 Dec 17.


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.

Clinical trials registration: NCT01058174.

Keywords: antifungal therapy; infection; liver transplant; micafungin; prophylaxis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use*
  • Chemoprevention / methods*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Echinocandins / adverse effects
  • Echinocandins / therapeutic use*
  • Female
  • Humans
  • Kidney Function Tests
  • Lipopeptides / adverse effects
  • Lipopeptides / therapeutic use*
  • Liver Function Tests
  • Liver Transplantation / adverse effects*
  • Male
  • Micafungin
  • Middle Aged
  • Mycoses / prevention & control*
  • Transplant Recipients*
  • Treatment Outcome
  • Young Adult


  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Micafungin

Associated data

  • ClinicalTrials.gov/NCT01058174