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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: Tacrolimus

• Study Type: Observational
• Enrollment (Actual): 398

Contacts and Locations

Study Locations

• France
  • Besancon, France
    • Site
  • Bordeaux, France
    • Site
  • Caen, France
    • Site
  • Chambray les Tours, France
    • Site
  • Clichy, France
    • Site
  • Creteil, France
    • Site
  • Grenoble, France
    • Site
  • Lille, France
    • Site
  • Limoges, France
    • Site
  • Lyon 3, France
    • Site
  • Lyon 4, France
    • Site
  • Marseille, France
    • Site
  • Montpellier, France
    • Site
  • Nice, France
    • Site
  • Paris, France
    • Site
  • Rennes, France
    • Site
  • Toulouse, France
    • Site
  • Villejuif, France
    • Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Liver transplant patients

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1:early conversion from Prograf® to Advagraf®; patients converted from Prograf® to Advagraf® in the first 3 months after transplantation	Drug: Tacrolimus; oral; Other Names: Prograf; FK506; Advagraf
2:late conversion from Prograf® to Advagraf®; patients converted from Prograf® to Advagraf® between 3 months and one year after transplantation	Drug: Tacrolimus; oral; Other Names: Prograf; FK506; 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

Collaborators and Investigators

• Sponsor: Astellas Pharma S.A.S.
• Investigators: Study Director: Medical and Scientific Affairs Manager, Transplantation, Astellas Pharma S.A.S.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2014
• Primary Completion (Actual): May 3, 2017
• Study Completion (Actual): May 3, 2017

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: May 19, 2014
• First Posted (Estimated): May 21, 2014

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Observational; Tacrolimus; France; Prograf; Pharmaco-epidemiology
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: FR-ADV-NI-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No