Clinical trial NCT01058174: Liver Transplant European Study Into the Prevention of Fungal Infection
Official title: Randomized, Open Label, Non-inferiority Study of Micafungin Versus Standard Care for the Prevention of Invasive Fungal Disease in High Risk Liver Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Transplantation
Mycoses
Keywords: Prophylaxis
Liver transplantation
Invasive Fungal Infection
Micafungin
Prevention
Mycoses
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2010-01-28
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Prevention of invasive fungal infection in high risk patients following liver transplant.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 'Clinical success' at the End of Prophylaxis as assessed by the Independent Data Review Board (IDRB).
timeFrame: up to 21 days
Secondary outcomes:
measure: Absence of a 'proven' or 'probable' Invasive Fungal Disease (IFD) at the End of Study as assessed by the IDRB
timeFrame: 3 months
measure: Absence of 'proven' or 'probable' IFD at the End of Prophylaxis and at the End of Study as assessed by the Investigator
timeFrame: up to 21 days & 3 months
measure: Time to 'proven' or 'probable' IFD
timeFrame: up to 3 months
measure: Fungal free survival at the End of Study and at the end of Long-term Follow-up
timeFrame: 3 months & 6 months
measure: Incidence of superficial fungal infection and colonization at the End of Prophylaxis as compared to Baseline
timeFrame: up to 21 days
Other outcomes:
Locations:
city: Innsbruck
country: Austria
city: Antwerpen
country: Belgium
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Paris
country: France
state: Villejuif Cedex
city: Clichy
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Budapest
country: Hungary
city: Dublin
country: Ireland
city: Milan
country: Italy
city: Padova
country: Italy
city: Torino
country: Italy
city: Udine
country: Italy
city: Coimbra
country: Portugal
city: Porto
country: Portugal
city: Bucharest
country: Romania
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Riyadh
country: Saudi Arabia
city: Santiago de Compostela
country: Spain
state: A Coruna
city: Barakald
country: Spain
state: Vicaya
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Stockholm
country: Sweden
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Use Central Contact
role: STUDY_DIRECTOR
References:
citation: Saliba F, Pascher A, Cointault O, Laterre PF, Cervera C, De Waele JJ, Cillo U, Langer RM, Lugano M, Goran-Ericzon B, Phillips S, Tweddle L, Karas A, Brown M, Fischer L; TENPIN (Liver Transplant European Study Into the Prevention of Fungal Infection) Investigators; TENPIN Liver Transplant European Study Into the Prevention of Fungal Infection Investigators. Randomized trial of micafungin for the prevention of invasive fungal infection in high-risk liver transplant recipients. Clin Infect Dis. 2015 Apr 1;60(7):997-1006. doi: 10.1093/cid/ciu1128. Epub 2014 Dec 17.