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

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

Author information

1
Hôpital Paul Brousse, Villejuif, France.
2
Charite Universitätsmedizin, Berlin, Germany.
3
Hôpital de Rangueil, Toulouse, France.
4
St Luc University Hospital, Université catholique de Louvain, Brussels, Belgium.
5
Hospital Clinic i Provincial, Barcelona, Spain.
6
Ghent University Hospital, Belgium.
7
Azienda Ospedaliera di Padova, Italy.
8
Semmelweis University, Budapest, Hungary.
9
Azienda Ospedaliero Universitaria Misericordia, Udine, Italy.
10
Karolinska University Hospital, Huddinge, Sweden.
11
Astellas Pharma Europe, Leiden, The Netherlands.
12
Astellas Pharma Europe Medical Affairs, Chertsey, United Kingdom.
13
Astellas Pharma Global Medical Affairs, Northbrook, Illinois.
14
University Medical Center Hamburg-Eppendorf, Germany.

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.

CLINICAL TRIALS REGISTRATION:

NCT01058174.

KEYWORDS:

antifungal therapy; infection; liver transplant; micafungin; prophylaxis

Comment in

PMID:
25520332
PMCID:
PMC4357288
DOI:
10.1093/cid/ciu1128
[Indexed for MEDLINE]
Free PMC Article

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