Micafungin as Antifungal Prophylaxis in High-Risk Liver Transplant Patients: A Randomised Multicentre Trial.

Abstract

Purpose: In the TENPIN study, micafungin was compared to centre-specific standard care (SC) prophylaxis in liver transplant patients at high risk of invasive fungal disease (IFD). Methods: Following transplantation, patients were randomised 1:1 to iv micafungin or iv SC (fluconazole, liposomal amphotericin B or caspofungin). Primary endpoint was clinical success (absence of proven/probable IFD and no initiation of additional antifungals) at end of prophylaxis (EOP). Micafungin was compared for non-inferiority (10% margin) vs SC in the per protocol set and confirmed in the full analysis set. Safety assessments (safety analysis set) included hepatic and renal function. Renal function was analysed post-hoc by calculating glomerular filtration rate (4-MDRD formula) in all patients and a subset not receiving post-operative renal replacement therapy at baseline. Results: The full analysis set comprised 344 patients without baseline IFD: micafungin, n=172 and SC, n=172. Baseline characteristics were well balanced between groups. Mean duration of exposure was 17±8 days. Clinical success in the per protocol set was 98.6% for micafungin (n=140) and 99.3% for SC (n=137) (difference [95% CI]: 0.7 [-2.7, 4.4]) and in the full analysis set was 96.5% and 93.6% (-2.9 [-8.0, 1.9]) demonstrating non-inferiority of micafungin to SC. Safety analysis set comprised 173 micafungin and 172 SC patients. There were no differences between treatment groups in hepatic function tests. Lower serum creatinine and urea levels at EOP suggested a trend for better renal function in micafungin- vs SC-treated patients. Post-hoc analysis showed higher mean glomerular filtration rate for micafungin vs SC in all patients (EOP: 93.77±4.85 vs 80.38±4.38 mL/min/1.73m2) and in those not receiving renal replacement therapy (EOP: 102.67±5.69 (n=133) vs 85.46±4.76 (n=142) mL/min/1.73m2; p=0.03 ANCOVA). Conclusion: Micafungin proved non-inferior to SC in prophylaxis of IFD in high-risk liver transplant patients. Renal function was better at EOP in micafungin- vs SC-treated patients. DISCLOSURES:Saliba, F.: Grant/Research Support, Astellas Pharma, Speaker fees, Novartis, Speaker fees, Roche, Speaker fees, Gambro, Speaker fees, Other, MSD, Speaker fees, Gilead, Speaker fees. Pascher, A.: Other, Astellas Pharma, Clinical study participation. Cointault, O.: Other, Astellas Pharma, Clinical study participation. De Waele, J.: Other, Astellas Pharma, Clinical study participation. Cervera, C.: Other, Astellas Pharma, Lecture fees/travel expenses, Pfizer, Lecture fees/travel expenses, Novartis, Lecture fees/travel expenses, Gilead, Travel expenses, Merck, Lecture fees/travel expenses, Genzyme, Lecture fees. Tweddle, L.: Employee, Astellas Europe. Karas, A.: Employee, Astellas Europe. Fischer, L.: Other, Astellas Pharma, Clinical study investigator.