Condition category
Injury, Occupational Diseases, Poisoning
Date applied
14/03/2007
Date assigned
28/03/2007
Last edited
02/09/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes