Liver Transplant European Study Into the Prevention of Fungal Infection (TENPIN)

Randomized, Open Label, Non-inferiority Study of Micafungin Versus Standard Care for the Prevention of Invasive Fungal Disease in High Risk Liver Transplant Recipients

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

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Mycoses
• Intervention / Treatment: Drug: micafungin; Drug: fluconazole; Drug: liposomal amphotericin B; Drug: caspofungin

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.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
• Belgium
  • Antwerpen, Belgium, 2650
  • Brussels, Belgium, 1200
  • Brussels, Belgium, 1070
  • Gent, Belgium, 9000
• France
  • Clichy, France, 32110
  • Paris, France, 75013
  • Toulouse, France, 31059
  • Villejuif Cedex
    • Paris, Villejuif Cedex, France, 94804
• Germany
  • Berlin, Germany, 13353
  • Hamburg, Germany, 20246
  • Hannover, Germany, 30625
  • Heidelberg, Germany, 69120
• Hungary
  • Budapest, Hungary, 1082
• Ireland
  • Dublin, Ireland, 4
• Italy
  • Milan, Italy, 20146
  • Padova, Italy, 35127
  • Torino, Italy, 10126
  • Udine, Italy, 33100
• Portugal
  • Coimbra, Portugal, 3000-075
  • Porto, Portugal, 4099-001
• Romania
  • Bucharest, Romania, 22328
• Russian Federation
  • Moscow, Russian Federation, 123182
  • Moscow, Russian Federation, 129090
  • St. Petersburg, Russian Federation, 197758
• Saudi Arabia
  • Riyadh, Saudi Arabia
• Spain
  • Barcelona, Spain, 08036
  • Cordoba, Spain, 14004
  • Madrid, Spain, 28034
  • Madrid, Spain, 28007
  • Valencia, Spain, 46009
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
  • Vicaya
    • Barakald, Vicaya, Spain, 48903
• Sweden
  • Stockholm, Sweden, 14186
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
  • London, United Kingdom, SE5 9RS

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: micafungin; intravenous infusion	Drug: micafungin; intravenous infusion; Other Names: Mycamine
Active Comparator: standard care; intravenous infusion	Drug: fluconazole; intravenous infusion; Other Names: Diflucan; Drug: liposomal amphotericin B; intravenous infusion; Other Names: AmBisome; Drug: caspofungin; intravenous infusion; Other Names: Cancidas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
'Clinical success' at the End of Prophylaxis as assessed by the Independent Data Review Board (IDRB).	up to 21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Absence of a 'proven' or 'probable' Invasive Fungal Disease (IFD) at the End of Study as assessed by the IDRB	3 months
Absence of 'proven' or 'probable' IFD at the End of Prophylaxis and at the End of Study as assessed by the Investigator	up to 21 days & 3 months
Time to 'proven' or 'probable' IFD	up to 3 months
Fungal free survival at the End of Study and at the end of Long-term Follow-up	3 months & 6 months
Incidence of superficial fungal infection and colonization at the End of Prophylaxis as compared to Baseline	up to 21 days

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2009
• Primary Completion (Actual): May 3, 2012
• Study Completion (Actual): May 3, 2012

Study Registration Dates

• First Submitted: January 26, 2010
• First Submitted That Met QC Criteria: January 26, 2010
• First Posted (Estimate): January 28, 2010

Study Record Updates

• Last Update Posted (Actual): March 11, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Liver transplantation; Micafungin; Prevention; Prophylaxis; Invasive Fungal Infection; Mycoses
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Micafungin; Caspofungin; Fluconazole; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: 9463-EC-0001; 2008-005214-49 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR