Contact information
Type
Scientific
Primary contact
Dr Ghent Cam
ORCID ID
Contact details
Section of hepatology
Department of Medicine
London Health Sciences Centre
339 Windermere Road
London
Ontario
N6A 5A5
Canada
cam.ghent@lhsc.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
In this study we investigate whether oral administration of ursodeoxycholic acid reduces the risk of rejection and recurrence of underlying disease in liver transplant recipients undergoing total immunosuppression withdrawal (TIW).
Ethics approval
Ethics approval received from the University of Western Ontario, London, Ontario, Canada on 01/01/1995. Patients were informed about possible consequences of immunosuppression withdrawal (rejection, recurrence of disease, renal function).
Study design
Randomised, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Condition
Liver transplantation, rejection, withdrawal of immunosuppressions
Intervention
26 liver recipients who had been free of rejection while on immunosuppressive agents for a minimum of two years will be randomised to receive either 15 mg/kg of ursodeoxycholic acid (UDCA) (N = 14) or identical placebo (N = 12) followed by sequential withdrawal of their immunosuppressive regimen over several months.
Prior to TIW a baseline liver biopsy was obtained and reviewed with a pathologist to exclude sub-clinical rejection and co-existent disease in the graft. Within one week of initiating TIW, patients underwent the following evaluations:
1. Alanine aminotransferase (ALT)
2. Aspartate aminotransferase (AST)
3. Alkaline phosphatase
4. Total bilirubin
5. Creatinine
6. Complete blood count (CBC)
7. Cyclosporin (CyA) levels by means of monoclonal antibody radioimmunoassay on whole blood (Cyclotrac, INCSTAR)
These same parameters were repeated every two weeks for the initial six months post-TIW and then monthly for a year thereafter. Liver biopsies were repeated in those who developed elevated liver enzymes (greater than 2 x normal) and in those who had completed six months of follow up with no immunosuppression other than the study medication. Secondary aims or endpoints such as development of renal failure, hypertension, extent of liver enzymes abnormalities as well as safety and compliance were assessed accordingly.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
1. Biochemical and histological evidence of rejection
2. Graft dysfunction without rejection
3. Recurrence of pre-transplant disease
4. Six months without immunosuppression and no rejection or dysfunction on repeat liver biopsy
Secondary outcome measures
1. Development of renal failure
2. Hypertension
3. Extent of liver enzymes abnormalities
4. Safety and compliance
Overall trial start date
01/01/1995
Overall trial end date
01/12/1996
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Recipients of liver transplantation at the University of Western Ontario, Canada who had stable graft function (no clinical or biochemical evidence of liver disease) for a minimum of two years were offered TIW if they met the following criteria:
1. No documented rejection episodes for at least 24 months prior to the study
2. A minimum post-transplant follow up period of at least 2 years
3. A history of compliance with medications, blood testing for laboratory analyses and in the case of patients transplanted for alcohol-induced liver disease, abstinence from all alcohol beverages during the study period
Participant type
Patient
Age group
Not Specified
Gender
Both
Target number of participants
46
Participant exclusion criteria
1. Patients requiring triple anti-rejection therapy for frequent or severe episodes of rejection in the past
2. More than one liver transplant
3. Requiring anti rejection therapy for non-liver disorders (psoriasis, rheumatoid arthritis [RA] etc)
Recruitment start date
01/01/1995
Recruitment end date
01/12/1996
Locations
Countries of recruitment
Canada
Trial participating centre
Section of hepatology
Ontario
N6A 5A5
Canada
Sponsor information
Organisation
University of Western Ontario (Canada)
Sponsor details
c/o Dr Ghent Cam
Section of hepatology
Department of Medicine
London Health Sciences Centre
339 Windermere Road
London
Ontario
N6A 5A5
Canada
cam.ghent@lhsc.on.ca
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
University of Western Ontario (Canada) - the Liver Unit
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list