Caspofungin as Prophylaxis in High Risk Liver Transplantation Recipients (CPHRLTX)

Pilot Study: Efficacy of Caspofungin for Antifungal Prophylaxis for Selected High Risk Liver Transplant Patients

The aim of the study is to determine viable use of caspofungin in post-OLTx patients, and to demonstrate in particular the effectiveness, understood as the ability to reduce the incidence of invasive fungal infections, and to assess the ability to reduce the risk and incidence of side effects (toxicity) which may arise in transplant patients treated with other drugs, especially in individuals recognized as high risk (e.g. renal failure).

Study Overview

• Status: Unknown
• Conditions: Mycoses; Fungemia
• Intervention / Treatment: Drug: Caspofungin

Detailed Description

The prophylactic use of anti-fungal drugs is crucial in order to decrease the incidence of invasive fungal infections in transplantation patients.

Invasive fungal infections (IFI) ---organ-related or systemic infections--- are in fact one of the most important causes of morbidity and mortality in patients undergoing solid organ transplantation (respectively, 70% and 100%).

The rationale of the proposed study is to evaluate a new protocol for the prevention of IFIs through the use of a newly introduced anti-fungal, caspofungin (commercial name: Cancidas), to be used for primary prophylaxis of fungal infections post-OLTx and to compare to drugs already in use (eg. amphotericin B, fluconazole), until 21 days after liver transplantation.

The aim of this study is determine viable use of caspofungin in post-OLTx patients, and to demonstrate in particular the effectiveness, understood as the ability to reduce the incidence of invasive fungal infections, and to assess the ability to reduce the risk and incidence of side effects (toxicity) which may arise in transplant patients treated with other drugs, especially in individuals recognized as high risk (e.g. renal failure).

The possibility of reducing the risk of fungal infections in liver transplant patients (usually between 7 and 42%) is therefore an important clinical goal.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Padova, Italy, 35128
    • Recruiting
    • Azienda Ospedaliera di Padova
    • Sub-Investigator: Marina Polacco, MD
    • Sub-Investigator: Davide Du Puis, MD
    • Sub-Investigator: Laura Saracino, MBS

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:

• patients shortlisted for liver transplantation
• negative pregnancy test for fertile female patients 7 days prior enrollment
• patients who can adequately communicate with study responsibles, who can understand and answer to protocol requirements

At least one of the following criteria:

• MELD score ≥25
• liver transplantation for acute liver failure
• liver re-transplantation
• fever without bacterial or viral infection
• biliodigestive
• re-laparatomy after LTx
• post LTx pancreatitis
• post LTx dialysis or renal insufficiency

Exclusion Criteria:

• Patients enrolled in other clinical trial or those having received other experimental drugs 4 weeks prior to enrollment
• Patients with a known fungal infection (based on the EORTC/MSG criteria)
• Patients with history of hypersensitivity to the drug, or other counterindications
• Patients with a diagnosed Severe Hepatic insufficiency (CTP >9)
• Physical or hematochemical alterations
• Clinically relevant psychological alterations in the 2 weeks preceding enrollment such as to interfere, in the researchers opinion, with the goal of the study
• Patients being treated with Ciclosporin A

Subjects being removed from the trial shall be replaced.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Caspofungin; Study group	Drug: Caspofungin; 50mg/dd for 21dd, starting within 24h from Liver Transplantation.; Other Names: Cancidas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive Fungal Infection Free follow-up	Invasive Fungal Infection free control 1 month after beginning treatment.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance to treatment.	Tolerance to treatment, with major focus on nephrotoxicity.	3 months
Study group mortality	Assessment of study group mortality, compared to control	3 months
Study group morbidity	Assessment of study group morbidity, compared to control	3 months
Invasive Fungal Infection-free percentage of study group	Invasive Fungal Infection-free percentage of study group, evaluated at 1 month from beginning of study and assessment of mortality and morbidity in the control group	1 month

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera di Padova
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Umberto Cillo, MD, Azienda Ospedaliera Universitaria di Padova; Principal Investigator: Daniele Neri, MD, Azienda Ospedaliera Universitaria di Padova

Publications and helpful links

Helpful Links

• Hepatobiliary surgery and Liver Transplantation Unit, University Hospital of Padua (Italy)

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ANTICIPATED): November 1, 2012
• Study Completion (ANTICIPATED): November 1, 2012

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (ESTIMATE): December 16, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 18, 2012
• Last Update Submitted That Met QC Criteria: July 17, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Invasive Mycosis; Organ Transplantation; Antifungal Agents; Liver Transplantation; Mycoses; Invasive fungal infections; Fungus Diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Invasive Fungal Infections; Mycoses; Fungemia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Caspofungin
• Other Study ID Numbers: 1768P; 2008-007950-36 (EUDRACT_NUMBER)