Anidulafungin Versus Fluconazole for the Prevention of Fungal Infections in Liver Transplant Recipients

Overview

The purpose of this study is to compare the efficacy of anidulafungin versus fluconazole for the prevention of fungal diseases in liver transplant recipients

Full Title of Study: “Anidulafungin Versus Fluconazole for the Prevention of Invasive Fungal Infections in High-risk Liver Transplant Recipients: a Randomized, Double-blind Trial”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Prevention
  • Masking: Triple (Participant, Care Provider, Investigator)
• Study Primary Completion Date: July 2013

Detailed Description

A number of well characterized risk factors have been shown to portend a high risk of opportunistic mycoses after liver transplantation. Retransplantation and renal failure are amongst the most significant risk factors for invasive fungal infections in these patients. Most Invasive fungal infections in these high-risk patients occur within the first month posttransplant. Studies utilizing universal prophylaxis have primarily employed fluconazole. A recent meta-analysis of prophylactic trials documented a beneficial effect on morbidity and attributable mortality, but an emergence of infections due to non-albicans Candida spp. in patients receiving prophylaxis. The availability of echinocandins has led to an expanded armamentarium of antifungal drugs with a potentially promising role as agents for targeted prophylaxis for invasive fungal infections in high-risk liver transplant recipients. Anidulafungin is unique amongst echinocandins in that it is eliminated from the body almost exclusively through biotransformation by slow non-enzymatic degradation in the blood, without hepatic metabolism or renal elimination. Anidulafungin has demonstrated good safety profile. We hypothesize that anidulafungin will be more effective and a better tolerated antifungal prophylactic agent in this setting.

Interventions

• Drug: Anidulafungin
  • 200 mg IV loading dose followed by 100 mg qd for 21 days
• Drug: Fluconazole
  • 400 mg IV for 21 days

Arms, Groups and Cohorts

• Experimental: anidulafungin
  • anti-fungal agent
• Active Comparator: Fluconazole
  • anti-fungal agent

Clinical Trial Outcome Measures

Primary Measures

• Frequency of Fungal Infection
  • Time Frame: 90 days post enrollment

Secondary Measures

• Need for Additional Antifungal Therapy
  • Time Frame: 90 days post enrollment

Participating in This Clinical Trial

Inclusion Criteria

• Liver transplant recipient at increased risk for infection increased risk include any of the following: – retransplantation – renal replacement therapy (dialysis), – post transplant abdominal surgery (within 21days) – receipt of corticosteroids for greater than 14 days within the 4 weeks -preceding transplant – ICU care for greater than 48 hours at the time of transplantation – colonization with Candida sps within 4 weeks of transplantation – requirement of 15 units or greater of packed red cell transfusions – Intraoperative time exceeding 6 hours Exclusion Criteria:

• Hypersensitivity to azole or echinocandin antifungal agents – receipt of systemic antifungal therapy within 4 weeks prior to transplantation

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of Pittsburgh
• Provider of Information About this Clinical Study
  • Principal Investigator: Nina Singh, MD – University of Pittsburgh
• Overall Official(s)
  • Nina Singh, MD, Principal Investigator, University of Pittaburgh, VA Pittsburgh Health Systems

Citations Reporting on Results

Winston DJ, Limaye AP, Pelletier S, Safdar N, Morris MI, Meneses K, Busuttil RW, Singh N. Randomized, double-blind trial of anidulafungin versus fluconazole for prophylaxis of invasive fungal infections in high-risk liver transplant recipients. Am J Transplant. 2014 Dec;14(12):2758-64. doi: 10.1111/ajt.12963. Epub 2014 Nov 6.