A Multicenter Study in Liver Transplant Patients Converted From Prograf® to Advagraf® During the First Post-transplantation Year

Study Overview
=================
Brief Summary
-----------------
A study in which two groups of patients will be analysed; patients converted from Prograf to Advagraf within the first 3 months after transplantation and patients converted from Prograf to Advagraf between 3 months and 1 year after transplantation.

Official Title
-----------------
A Cohort Study in Liver Transplant Patients Converted From a Tacrolimus Twice a Day (Prograf®) to Tacrolimus Once a Day (Advagraf®). French, Multisite, Observational Study

Conditions
-----------------
Liver Transplantation

Intervention / Treatment
-----------------
* Drug: Tacrolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient with a liver transplant performed in the previous year and for whom the conversion from Prograf® to Advagraf® was decided by the physician. Exclusion Criteria: Patient participating in an interventional clinical trial at the time of enrolment into the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1:early conversion from Prograf® to Advagraf®<br>patients converted from Prograf® to Advagraf® in the first 3 months after transplantation | Drug: Tacrolimus<br>* oral<br>* Other names: Advagraf;|
| 2:late conversion from Prograf® to Advagraf®<br>patients converted from Prograf® to Advagraf® between 3 months and one year after transplantation | Drug: Tacrolimus<br>* oral<br>* Other names: Advagraf;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion ratio of the daily dose of tacrolimus (mg Prograf® / mg Advagraf®) | Percentage of patients with a conversion ratio of tacrolimus dose of 1mg/1mg and percentage of patients with a ratio differing from 1mg/1mg | At baseline | 
| Time of the first tacrolimus trough level (C0) after conversion | Number of days between the conversion date and the date of the first determination of C0 after conversion | From baseline to first determination of C0 (up to 6 months) | 
| Number of additional visits considered by the physicians to be due to the conversion (if required) | Percentage of patients with additional visit(s) and percentage of patients without an additional visit | At 6 months and at 1 year follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reasons for conversion | Number of pills, number of treatment intake, treatment compliance, physician request, patient request, safety of treatment, center practice | At baseline | 
| Patient profile | Sociodemographic data, history of transplantation, comorbidities, complications after transplantation, risk factors, concomitant treatments (other than immunosuppressive protocols) and modification, if required, at 6 months and 1 year after conversion | At baseline | 
| Collection of immunosuppressive protocol details | Date of initiation of treatment with Advagraf® Target tacrolimus C0 (with Prograf® and with Advagraf® and recommendations for administration) Daily dose of Advagraf® Adjustments to Advagraf® dose since the previous visit: date, doses and reason for adjustment Type and dose of immunosuppressive drugs combined with Advagraf® Modification of the immunosuppressive regimen at 6 months and 1 year after conversion (if applicable) since the previous visit: date, modified treatment, type of modification, reason for modification Immunosuppressive regimen at the end of the visit at 6 months and 1 year after conversion, modified treatment, type of modification, reason for modification | At baseline, 6 months and 1 year follow-up visit | 
| Time to reach steady state |  | From baseline to first determination of C0 (up to 6 months) | 
| Dose ratio at steady state | Ratio of daily dose of tacrolimus during achievement of steady state: mg Prograf® at conversion/mg Advagraf® during achievement of steady state. Percentage of patients with a ratio of 1mg/1mg and percentage of patients with a ratio differing from 1mg/1mg | From baseline and up to 6 months post-conversion | 
| The Intra -Patient Variability (IPV) of tacrolimus in patients on Prograf® and Advagraf ® |  | At baseline (Prograf) and during the 45 days after conversion (Advagraf) | 
| Latest available laboratory data with Prograf® before conversion and with Advagraf® | Values and dates for renal parameters, liver parameters, blood glucose and Hepatitis C viral load | At baseline, 6 months and 1 year follow-up visit | 
| Compliance with treatment at conversion | Compliance with treatment at conversion (with Prograf® and only in group 2) and at 1 year after conversion (with Advagraf® for both groups) will be assessed using the Morisky questionnaire and a score will be calculated | At baseline and at 1 year after conversion | 
| Patients' quality of life at conversion | Patients' quality of life at conversion (with Prograf® only in group 2) and at 1 year after conversion (with Advagraf® for both groups) will be assessed using the European Quality of Life-5 Dimensions 5 level (EQ5D-5L) questionnaire | At baseline and at 1 year after conversion | 
| Rate of acute rejection proven by biopsy (BPAR), graft survival rate and patient survival rate | Will be assessed on the basis of the number of acute rejections confirmed by biopsy and recorded adverse events and adverse reactions | 6 months and 1 year | 
| Occurrence of adverse events and/or effects |  | From baseline until 1 year follow-up visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
France, Prograf, Pharmaco-epidemiology, Tacrolimus, Observational