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

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

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.

Study Overview

• Status: Completed
• Conditions: Fungal Infection; Liver Disease
• Intervention / Treatment: Drug: Anidulafungin; Drug: Liposomal amphotericin B

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital Clínic i Provincial
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital De Bellvitge
  • Bilbao, Spain
    • Hospital de Cruces
  • Córdoba, Spain
    • Hospital Reina Sofia
  • La Coruña, Spain
    • Complexo Hospitalario de A Coruna
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Hospital Doce de Octubre
  • Malaga, Spain
    • Hospital Carlos Haya
  • Oviedo, Spain
    • Hospital Central de Asturias
  • Santander, Spain
    • Hospital Marques de Valdecilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anidulafungin; Anidulafungin IV once a day: initial dose 200 mg/day, following doses 100 mg/day.	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 Names: Ecalta
Active Comparator: Liposomal Amphotericin B; Liposomal amphotericin B once a day: 3 mg/kg/day	Drug: Liposomal amphotericin B; Liposomal amphotericin B once a day for 14 days: 3 mg/kg/day. IV administration during 60 minutes.; Other Names: AmBisome

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA
• Collaborators: Pfizer
• Investigators: Study Director: Carlos Cervera, MD, Hospital Clínic i Provincial; Principal Investigator: Asuncion Moreno, MD, Hospital Clínic i Provincial; Principal Investigator: Carmen Fariñas, MD, Hospital Marques de Valdecilla

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (Estimate): February 24, 2011

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Liver transplantation; Liposomal Amphotericin B; Hepatic transplant; Antifungal prophylaxis; Anidulafungin
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Bacterial Infections and Mycoses; Liver Diseases; Mycoses; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Anidulafungin; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: GESITRA 0110; 2011-000804-17 (EudraCT Number)