Background: Invasive fungal disease (IFD) following liver transplantation (LTx) has significant morbidity and mortality. In TENPIN, a Phase IIIb international, multicenter, randomized, open-label trial, the efficacy and safety of micafungin was assessed vs standard care (SC) in the prophylaxis of LTx pts considered at high risk of IFD. Methods: After LTx, pts were randomised 1:1 to iv micafungin 100mg (2.0mg/kg in pts 8804;40kg) once daily (od) or iv SC (fluconazole 200-400mg od; liposomal amphotericin B [L-AmB] 1-3mg/kg/day; or caspofungin 70mg loading, 50mg maintenance od). The primary endpoint was clinical success (absence of a proven/probable IFD and no additional antifungals) at end of prophylaxis (EoP). Micafungin was compared for non-inferiority (10% margin) vs SC in the per protocol set (PPS) and confirmed in the full analysis set (FAS). Safety assessments were adverse events (AE) and liver and renal function. Results: 344 patients without baseline IFD received micafungin (n=172) or SC (n=172). Baseline characteristics were well balanced between groups. Mean duration of exposure was 17Â±8 days. Clinical success at EoP was 98.6% for micafungin (n=140) and 99.3% for SC (n=137) (difference [95% CI]: 0.7 [-2.7, 4.4]) in the PPS and 96.5% and 93.6% (-2.9 [-8.0, 1.9]) in the FAS demonstrating non-inferiority of micafungin to SC. At EoP there were 4 Aspergillus and 8 Candida infections overall. 240 (70%) patients completed prophylaxis. Main reasons for discontinuation of micafungin or SC were AE (13.4% and 17.4%), lack of efficacy (2.3% and 4.7%) or withdrawal of consent (4.7% and 0%). In the safety population (n=345), incidences of drug-related AE for micafungin and SC were 11.6% and 16.3%, drug-related serious AE were 5.8% and 4.1%, and drug-related AE leading to discontinuation were 6.4% and 11.6%. Liver and renal function tests were similar between groups. Conclusions: In both groups, the rate of IFD was low. Micafungin proved non-inferior to SC in prophylaxis of IFD in high-risk LTx pts. Safety was similar between groups. Micafungin may provide a useful alternative to fluconazole and L-AmB in these pts.
Full conference title:
53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC, 53rd (2013)