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A Multicenter, Randomized, Open-Label Study to Compare Micafungin with Fluconazole in the Prophylaxis of Invasive Fungal Infections in Living-Donor Liver Transplant Recipients

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

Although invasive fungal infections (IFIs) contribute to substantial morbidity and mortality in liver transplant recipients, only a few randomized studies analyzed the results of antifungal prophylaxis with echinocandins. The aim of this open-label, non-inferiority study was to evaluate the efficacy and safety of micafungin in the prophylaxis of IFIs in living-donor liver transplantation recipients (LDLTRs), with fluconazole as the comparator.

Methods

LDLTRs (N = 172) from five centers were randomized 1:1 to receive intravenous micafungin 100 mg/day or fluconazole 100~200 mg/day (intravenous or oral). A non-inferiority of micafungin was tested against fluconazole.

Results

The per-protocol set included 144 patients without major clinical trial protocol violations: 69 from the micafungin group and 75 from the fluconazole group. Mean age of the study patients was 54.2 years and mean model for end-stage liver disease (MELD) score amounted to 16.5. Clinical success rates in the micafungin and fluconazole groups were 95.65% and 96.10%, respectively (difference: − 0.45%; 90% confidence interval [CI]: − 6.93%, 5.59%), which demonstrated micafungin’s non-inferiority (the lower bound for the 90% CI exceeded − 10%). The study groups did not differ significantly in terms of the secondary efficacy endpoints: absence of IFIs at the end of the prophylaxis and the end of the study, time to proven IFI, fungal-free survival, and adverse reactions. A total of 17 drug-related adverse events were observed in both groups; none of them was serious and all resolved.

Conclusion

Micafungin can be used as an alternative to fluconazole in the prevention of IFIs in LDLTRs.

Clinical Trials Registration

NCT01974375.

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Abbreviations

ADR:

Adverse drug reaction

AE:

Adverse event

CI:

Confidence interval

CMH:

Cochran-Mantel-Haenszel

CMV:

Cytomegalovirus

EBV:

Epstein–Barr virus

EOP:

End of the prophylaxis

EORTC/MSG:

European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group

EOS:

End of the study

FAS:

Full analysis set

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

IDSA:

Infectious Diseases Society of America

IFI:

Invasive fungal infection

LB:

Lower bound

LDLTRs:

Living-donor liver transplantation recipients

LTR:

Liver transplant recipients

MELD:

Model for end-stage liver disease

NC:

Not calculated

PPS:

Per protocol set

SAE:

Serious adverse event

SD:

Standard deviation

TEAE:

Treatment-emergent adverse event

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Funding

This study was funded by Astellas Pharma Korea, Inc. (AKR-MYC-2011-04).

Author information

Authors and Affiliations

  1. Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea

    Woo-Hyoung Kang, Gi-Won Song & Sung-Gyu Lee

  2. Department of Surgery, College of Medicine, Seoul National University, Seoul, South Korea

    Kyung-Suk Suh, Kwang-Woong Lee & Nam-Joon Yi

  3. Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea

    Jae Won Joh & Jong Man Kim

  4. Department of Surgery and Digestive Disease Institute, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Choon Hyuck David Kwon

  5. Department of Surgery, College of Medicine, Catholic University of Daegu, Daegu, South Korea

    Dong Lak Choi & Joo Dong Kim

  6. Department of Surgery, College of Medicine, Yonsei University, Seoul, South Korea

    Myoung Soo Kim

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  1. Woo-Hyoung Kang
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Contributions

G-W S, S-G L, and W-H K: Substantial contributions to the conception or design of the work; G-W S, N-J Y, J W J, D L C, and M S K: Data acquisition; G-W S, S-G L, K-S S, K-W L, C H D K, J M K, J D K, and M S K: Analysis, or interpretation of data; W-H K and G-W S: Drafting the work or revising it critically for important intellectual content; All 12 authors: Final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Gi-Won Song.

Ethics declarations

The protocol of the study was approved by the institutional review board of each study site.

Conflict of Interest

The authors declare that they have no competing interests.

The authors of this manuscript have no conflicts of interest to disclose as described by the Journal of Gastrointestinal Surgery.

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Kang, WH., Song, GW., Lee, SG. et al. A Multicenter, Randomized, Open-Label Study to Compare Micafungin with Fluconazole in the Prophylaxis of Invasive Fungal Infections in Living-Donor Liver Transplant Recipients. J Gastrointest Surg 24, 832–840 (2020). https://doi.org/10.1007/s11605-019-04241-w

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