Assessment Of the Safety and Benefit of Prospective Immunosuppressive Drug Withdrawal in Liver Transplantation and Prediction of Operational Tolerance

Summary

In liver transplantation up to 20% of recipients can completely discontinue immunosuppressive therapy maintaining normal graft function, and are conventionally considered as operationally tolerant. Discontinuation of immunosuppressive drugs in operationally tolerant recipients could lessen the side effects of chronic immunosuppressive therapy. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients.

The main objective of this study is to establish the safety of attempting immunosuppressive (IS) drug withdrawal in stable liver transplant recipients, using standard clinical, biological and histopathological methods, to screen and follow-up patients, and to confirm the benefit of maintaining immunosuppressive drug interruption in patients who are tolerant to their liver transplant. The secondary objective of this study is to identify predictive factors of operational tolerance and to attempt to develop a multi-parameter "decision rule" to predict patient tolerance or non-tolerance in order to improve patient screening and follow-up. In a diagnostic observational sub-study, peripheral blood and liver tissue samples collected before immunosuppressive drug withdrawal will be employed to validate the diagnostic accuracy of a previously identified set of tolerance biomarkers and to identify potential new biomarkers capable of predicting the outcome of the immunosuppressive withdrawal protocol.

Conditions

• Liver Transplantation

Interventions

PROCEDURE

Gradual immunosuppression drug withdrawal

After the obtention of biological samples (peripheral blood, liver tissue), enrolled patients undergo gradual weaning of all immunosuppressive therapy over a 6-9 month period under close medical supervision.

Sponsors & Collaborators

• Fondo de Investigacion Sanitaria

  collaborator OTHER

• European Commission

  collaborator OTHER

• TcLand Expression S.A.

  collaborator INDUSTRY

• Hospital Clinic of Barcelona

  lead OTHER

Principal Investigators

• Alberto Sanchez-Fueyo, MD · Hospital Clinic Barcelona / IDIBAPS, Barcelona, Spain

• Giuseppe Tisone, MD · University Tor Vergata, Rome, Italy

• Jacques Pirenne, MD · Abdominal Transplant Surgery Department, University Hospitals Leuven, Belgium

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-11-30

Primary Completion

2010-09-30

Completion

2012-12-31

Countries

• Spain

Study Locations