Liver Transplant European Study Into the Prevention of Fungal Infection

Condition(s) targeted: Liver Transplantation; Mycoses

Intervention: micafungin (Drug); fluconazole (Drug); liposomal amphotericin B (Drug); caspofungin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Astellas Pharma Inc

Official(s) and/or principal investigator(s):
Use Central Contact, Study Director, Affiliation: Astellas Pharma Europe Ltd.

Prevention of invasive fungal infection in high risk patients following liver transplant.

Official title: Randomized, Open Label, Non-inferiority Study of Micafungin Versus Standard Care for the Prevention of Invasive Fungal Disease in High Risk Liver Transplant Recipients

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: 'Clinical success' at the End of Prophylaxis as assessed by the Independent Data Review Board (IDRB).

Secondary outcome:

Absence of a 'proven' or 'probable' Invasive Fungal Disease (IFD) at the End of Study as assessed by the IDRB

Absence of 'proven' or 'probable' IFD at the End of Prophylaxis and at the End of Study as assessed by the Investigator

Time to 'proven' or 'probable' IFD

Fungal free survival at the End of Study and at the end of Long-term Follow-up

Incidence of superficial fungal infection and colonization at the End of Prophylaxis as compared to Baseline

Detailed description: After receiving liver transplant, subjects will be randomized to one of the two treatment arms. Study drugs will be administered for a period of 21 days, or until hospital discharge, whichever occurs first. Additionally, mortality data will be collected at the Long-term Follow-up.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Undergoing orthotopic whole or split liver allograft transplantation

- Patients at 'high risk' of invasive fungal infection due to the presence of at least

one of the following risk factors:

- Re-transplantation

- Acute liver failure

- Pre- or post-operative renal impairment (defined as creatinine clearance ≤40

ml/min) or need for renal replacement therapy

- Admission to Intensive Care Unit (ICU) for greater than 48 hours prior to liver

transplant

- Re-operation (abdominal surgery) within 5 days of liver transplant

- Presence of choledocojejunostomy

- Perioperative colonization with fungi, defined as two or more positive clinical

site surveillance cultures for Candida spp., obtained within 96 hours before or after liver transplant

- Need for prolonged mechanical ventilation for greater than 48 hours following

liver transplant

- Transfusion intraoperatively of 20 or more units of cellular blood products

- Female subject of childbearing potential must have a negative urine or serum

pregnancy test prior to randomization and must agree to maintain effective birth control during the study Exclusion Criteria:

- Any systemic antifungal therapy (excluding fluconazole or oral nystatin for a maximum

of 7 days) within 14 days prior to randomization

- Evidence of documented ('proven' or 'probable') or suspected ('possible') IFD

(according to the EORTC/MSG criteria)

- Allergy, hypersensitivity, or any serious reaction to an echinocandin antifungal, or

any of the study drugs or their excipients

Innsbruck 6020, Austria

Antwerpen 2650, Belgium

Brussels 1070, Belgium

Brussels 1200, Belgium

Gent 9000, Belgium

Clichy 32110, France

Paris 75013, France

Toulouse 31059, France

Berlin 13353, Germany

Hamburg 20246, Germany

Hannover 30625, Germany

Heidelberg 69120, Germany

Budapest 1082, Hungary

Dublin 4, Ireland

Milan 20146, Italy

Padova 35127, Italy

Torino 10126, Italy

Udine 33100, Italy

Coimbra 3000-075, Portugal

Porto 4099-001, Portugal

Bucharest 22328, Romania

Moscow 123182, Russian Federation

Moscow 129090, Russian Federation

St. Petersburg 197758, Russian Federation

Riyadh, Saudi Arabia

Barcelona 08036, Spain

Cordoba 14004, Spain

Madrid 28034, Spain

Madrid 28007, Spain

Valencia 46009, Spain

Stockholm 14186, Sweden

Birmingham B15 2TH, United Kingdom

London SE5 9RS, United Kingdom

Santiago de Compostela, A Coruna 15706, Spain

Barakald, Vicaya 48903, Spain

Paris, Villejuif Cedex 94804, France

Link to Results on JAPIC

Link to results on Astellas Clinical Study Results website

Starting date: December 2009
Last updated: June 5, 2015