Liver Transplant European Study Into the Prevention of Fungal Infection

Phase 3

Completed

• Conditions: Liver Transplantation; Mycoses
• Interventions: Drug: micafungin; Drug: fluconazole; Drug: liposomal amphotericin B; Drug: caspofungin

• Registration Number: NCT01058174
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-12-15
• Study First Submitted: 2010-01-26
• Study First Submitted QC: 2010-01-26
• Study First Posted: 2010-01-28
• Primary Completion: 2012-05-03
• Study Completion: 2012-05-03
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-15
• Last Update Posted: 2024-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 350

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
micafungin	micafungin	intravenous infusion
standard care	liposomal amphotericin B	intravenous infusion
standard care	fluconazole	intravenous infusion
standard care	caspofungin	intravenous infusion

Primary Outcome Measures

Name	Time	Method
'Clinical success' at the End of Prophylaxis as assessed by the Independent Data Review Board (IDRB).	up to 21 days

Secondary Outcome Measures

Name	Time	Method
Absence of 'proven' or 'probable' IFD at the End of Prophylaxis and at the End of Study as assessed by the Investigator	up to 21 days & 3 months
Fungal free survival at the End of Study and at the end of Long-term Follow-up	3 months & 6 months
Absence of a 'proven' or 'probable' Invasive Fungal Disease (IFD) at the End of Study as assessed by the IDRB	3 months
Time to 'proven' or 'probable' IFD	up to 3 months
Incidence of superficial fungal infection and colonization at the End of Prophylaxis as compared to Baseline	up to 21 days