Anidulafungin vs Amphotericin B Safety in High Risk Hepatic Transplant Recipients

Study Overview
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Brief Summary
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The study is a randomized, open-label safety study comparing the use of anidulafungin (200 mg i.v. as initial dose and 100 mg/d i.v. in subsequent doses) vs liposomal amphotericin B (3 mg/kg/d i.v.) in hepatic transplant recipients who have high risk of fungal infection.

Official Title
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Multicenter, Randomized, Open-label Clinical Trial to Compare Anidulafungin Versus Amphotericin B Safety in High Risk Hepatic Transplant Recipients

Conditions
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Liver Disease, Fungal Infection

Intervention / Treatment
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* Drug: Anidulafungin
* Drug: Liposomal amphotericin B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old Signature of ICF Negative pregnancy test (women of child bearing potential) Patients who comply with at least one of the following (A or B): A: One of the following criteria (major criteria): Re-transplant due to severe dysfunction of a previous hepatic graft Requirement of any renal substitutive therapy, including dialysis or hemofiltration Fulminant hepatitis requiring hepatic transplant B: Two of the following criteria (minor criteria): Post-transplant renal impairment (defined as CrCl< 50 mL/min) 30 days after transplantation Intra surgery blood transfusion of at least 40 units Choledochal jejunectomy 2 or more Candida sp cultures (nasal, pharynx, rectal) from 48 hours pre- to 48 hours post-hepatic transplant Post transplant re-intervention (laparotomy) Exclusion Criteria: Hypersensibility to amphotericin B or candin Patients who have received any other antifungal (excluding fluconazole or oral nystatin for a maximum of 7 days) Documented or suspected fungal infection Pregnant women of women who do not accept to us a valid anticonceptive method Any other disease or medical condition that makes the patient not adequate to participate in the trial

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anidulafungin<br>Anidulafungin IV once a day: initial dose 200 mg/day, following doses 100 mg/day. | Drug: Anidulafungin<br>* Anidulafungin once a day for 14 days: initial dose 200 mg/day IV administered in 180 minutes. Following doses 100 mg/day IV administered in 90 minutes.<br>* Other names: Ecalta;|
| Active Comparator: Liposomal Amphotericin B<br>Liposomal amphotericin B once a day: 3 mg/kg/day | Drug: Liposomal amphotericin B<br>* Liposomal amphotericin B once a day for 14 days: 3 mg/kg/day. IV administration during 60 minutes.<br>* Other names: AmBisome;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal impairment/renal function deterioration | Compare the development of renal imparment or deterioration of baseline renal function in hepatic transplat recipients who receive anidulafungin or liposomal amphotericin B | 14 days | 
| Number of infusion related adverse events | Compare the development of infusion related adverse events in hepatic transplat recipients who receive anidulafungin or liposomal amphotericin B | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment discontinuation | Compare the proportion of patiens who discontinue antifungal profilaxis in both arms | 14 days | 
| Hepatic toxicity | Compare the emergence of hepatic toxicity in both arms | 14 days | 
| Invasive fungal infection | Compare the incidence of early (first 12 weeks) and delayed (until week 24) invasive fungal infection between both arms | Week 12 and week 24 | 
| Mortality | Compare the mortality rate (both global and fungal infection related) between both arms 24 weeks after transplantation | 24 weeks post transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplantation, Hepatic transplant, Antifungal prophylaxis, Anidulafungin, Liposomal Amphotericin B