Anidulafungin vs Amphotericin B Safety in High Risk Hepatic Transplant Recipients (AVALTRA)

• Renal impairment/renal function deterioration [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  Compare the development of renal imparment or deterioration of baseline renal function in hepatic transplat recipients who receive anidulafungin or liposomal amphotericin B
• Number of infusion related adverse events [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  Compare the development of infusion related adverse events in hepatic transplat recipients who receive anidulafungin or liposomal amphotericin B

• Renal impairment/renal function deterioration [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  Compare the development of renal imparment or deterioration of baseline renal funcion in hepatic transplat recipients who receive anidulafungin or liposomal anfotericin B
• Number of infusion related adverse events [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  Compare the development infusion related adverse events in hepatic transplat recipients who receive anidulafungin or liposomal anfotericin B

• Treatment discontinuation [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  Compare the proportion of patiens who discontinue antifungal profilaxis in both arms
• Hepatic toxicity [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  Compare the emergence of hepatic toxicity in both arms
• Invasive fungal infection [ Time Frame: Week 12 and week 24 ] [ Designated as safety issue: Yes ]
  Compare the incidence of early (first 12 weeks) and delayed (until week 24) invasive fungal infection between both arms
• Mortality [ Time Frame: 24 weeks post transplantation ] [ Designated as safety issue: Yes ]
  Compare the mortality rate (both global and fungal infection related) between both arms 24 weeks after transplantation

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.

• Liver Disease
• Fungal Infection

• Drug: Anidulafungin
  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.
  Other Name: Ecalta
• Drug: Liposomal amphotericin B
  Liposomal amphotericin B once a day for 14 days: 3 mg/kg/day. IV administration during 60 minutes.
  Other Name: AmBisome

• Experimental: Anidulafungin
  Anidulafungin IV once a day: initial dose 200 mg/day, following doses 100 mg/day.
  Intervention: Drug: Anidulafungin
• Active Comparator: Liposomal Amphotericin B
  Liposomal amphotericin B once a day: 3 mg/kg/day
  Intervention: Drug: Liposomal amphotericin B

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