Liver Transplant European Study Into the Prevention of Fungal Infection

Study Overview
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Brief Summary
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Prevention of invasive fungal infection in high risk patients following liver transplant.

Detailed Description
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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.

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

Conditions
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Mycoses, Liver Transplantation

Intervention / Treatment
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* Drug: micafungin
* Drug: fluconazole
* Drug: liposomal amphotericin B
* Drug: caspofungin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: micafungin<br>intravenous infusion | Drug: micafungin<br>* intravenous infusion<br>* Other names: Mycamine;|
| Active Comparator: standard care<br>intravenous infusion | Drug: fluconazole<br>* intravenous infusion<br>* Other names: Diflucan;Drug: liposomal amphotericin B<br>* intravenous infusion<br>* Other names: AmBisome;Drug: caspofungin<br>* intravenous infusion<br>* Other names: Cancidas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 'Clinical success' at the End of Prophylaxis as assessed by the Independent Data Review Board (IDRB). |  | up to 21 days | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylaxis, Liver transplantation, Invasive Fungal Infection, Micafungin, Prevention, Mycoses