Randomized Trial of Micafungin for the Prevention of Invasive Fungal Infection in High-Risk Liver Transplant Recipients
Saliba F, Pascher A, Cointault O, et al.Clinical Infectious Diseases 2014; 60(7): 997-1006
Aims
To demonstrate noninferiority of the echinocandin micafungin versus centre-specific standard care for Invasive Fungal Infection (IFI) prevention in liver transplant recipients deemed at high risk of IFI.
Interventions
To demonstrate noninferiority of the echinocandin micafungin versus centre-specific standard care for Invasive Fungal Infection (IFI) prevention in liver transplant recipients deemed at high risk of IFI.
Participants
344 patients aged ≥18 years undergoing orthotopic whole or split liver allograft transplant with the presence of at least 1 IFI risk factor.
Outcomes
The outcomes measured were efficacy and safety. The primary efficacy outcome measured was clinical success rate. Secondary efficacy outcomes included absence of a proven or probable IFI, absence of initiation of antifungal therapy, time to proven or probable IFI, fungal-free survival at end of study, and end of long-term follow-up. Safety outcomes measured were treatment-emergent adverse events, hepatic and renal function, and deaths.
Follow-up
6 months
CET Conclusions
The TENPIN study randomised 344 high-risk liver transplant patients to either micafungin prophylaxis or standard care in each of the participating centres, which varied between fluconazole, liposomal amphotericin B, or caspofungin. The study had a non-inferiority design. Primary outcome (a composite of proven invasive fungal infection (IFI), probable IFI or need for additional antifungal infection) did not differ between groups. Adverse event profiles were similar between arms, although renal function was improved in the micafungin arm. This study is the first randomised trial to investigate the use of echinocandins in liver transplantation, and appears to support their role as an alternative prophylactic strategy in high risk patients. There are limitations - the heterogeneous nature of the standard care arm, in both dose and agent, makes interpretation of the results difficult if one wants to compare the efficacy of micafungin directly with another agent. As standard care varied by transplant centre, and the risk of IFI may also vary by centre depending on local factors, this may skew the results. The open-label study design, given the objective nature of a clinical diagnosis of probable IFI, is also a limitation. In order to counter this latter limitation, a blinded independent data review board also assessed diagnosis of IFI using published criteria.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT01058174; EudraCT 2008 - 005214-49