Randomised controlled trial of total immunosuppression withdrawal in liver transplant recipients: role of ursodeoxycholic acid
| ISRCTN | ISRCTN16781831 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16781831 |
| Secondary identifying numbers | N/A |
- Submission date
- 14/03/2007
- Registration date
- 28/03/2007
- Last edited
- 02/09/2008
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Injury, Occupational Diseases, Poisoning
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Ghent Cam
Scientific
Scientific
Section of hepatology
Department of Medicine, London Health Sciences Centre
339 Windermere Road, London
Ontario
N6A 5A5
Canada
| cam.ghent@lhsc.on.ca |
Study information
| Study design | Randomised, placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Scientific title | |
| Study objectives | 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(s) | 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). |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 01/01/1995 |
| Completion date | 01/12/1996 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Both |
| Target number of participants | 46 |
| Key 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 |
| Key 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) |
| Date of first enrolment | 01/01/1995 |
| Date of final enrolment | 01/12/1996 |
Locations
Countries of recruitment
- Canada
Study participating centre
Section of hepatology
Ontario
N6A 5A5
Canada
N6A 5A5
Canada
Sponsor information
University of Western Ontario (Canada)
University/education
University/education
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 | |
"ROR" |
https://ror.org/02grkyz14 |
Funders
Funder type
University/education
University of Western Ontario (Canada) - the Liver Unit
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
