English: Advagraf, liver transplantation, optimizing immunosuppressive therapy Dutch:Advagraf, levertransplantatie, optimaliseren immunosuppressieve therapie, effectiviteit en veiligheid
Conditions
Interventions
Low-dose tacrolimus in combination with low dose sirolimus versus standard dose of tacrolimus.
All participants will receive the same medication at first. Induction with basiliximab and mycophenolate
at day 4 +/- 1 start twice daily tacrolimus (5-10 ng/ml)
Between day 14-21 conversion to once daily Advagraf (5-10 ng/ml)
MPA stop at day 30
steroids 10 mg daily.
Randomization at 90 days (range 80-100 days ) after LTx.
Arm I: Continue standard dose once daily Advagraf (5- 10 ng/ml)
steroids 7.5 mg and lower or discontinue steroids at 180 days after transplantation at discretion of physician.
Arm II: Conversion to once daily 2 mg (low dose) Sirolimus (3-5 ng/ml) and 2 mg (low do
7.5 mg steroids and lower or discontinue steroids at 180 days after transplantation at discretion of physician.
Sponsors
Foundation for Liver and Gastrointestinal Research (SLO)
Department of Gastroenterology & Hepatology
Erasmus Medical Center Rotterdam
‘s Gravendijkwal 230, Room HA 204
3015 CE Rotterdam, The Netherlands
Tel: +31 10 703 5942
Fax: +31 10 436 5916
Eligibility
Inclusion criteria
Inclusion criteria: 1. Primary liver transplantation or retransplantation within 14 days after first transplantation; 2. Use of Advagraf at least 2 weeks prior to randomization; 3. Patent hepatic artery; 4. Closed abdominal wound; 5. Stable graft function; 6. Positive informed consent at time of randomization; 7. Age 18-70 years.
Exclusion criteria
Exclusion criteria: 1. Treatment with investigational drugs within 3 months before start of therapy; 2. Multi organ transplantation; 3. cGFR 800 mg/24 h; 5. Hyperlipidemia refractory to optimal medical management (Cholesterol > 9 mmol/l and/or triglycerides > 8.5 mmol/l). Patients with controlled hyperlipidemia are acceptable at the time of randomization; 6. Known hypersensitivity to sirolimus or its derivatives; 7. Thrombocytes < 50 x 109 /L; 8. Leukocytes < 2.5 x 109 /L; 9. Haemoglobin < 6 mmol/L; 10. Biopsy proven rejection 2 weeks prior to randomization; 11. HIV positivity; 12. Signs of recurrent or de novo cancer; 13. Patients with non-HCC malignancies within the past 5 years (excluding successfully treated squamous cell carcinoma and basal cell carcinoma of the skin); 14. Evidence of significant local or systemic infection; 15. Pregnancy or breast feeding; 16. Women of child-bearing potential not willing to take oral contraception; 17. Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with cGFR < 60ml/min at 36 months after transplantation. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Incidence of and time to de novo malignancy at 36 months after transplantation; 2. Incidence of and time to recurrent malignancy; 3. Biopsy proven rejection; 4. Retransplantation; 5. Percentage of patients with cGFR <60ml/min at 12 and 24months after transplantation; 6. cGFR at 12, 24 and 36 months after transplantation; 7. Incidence of De novo diabetes mellitus at 12, 24 and 36 months after transplantation; 8. Quality of life using SF-36 questionnaires at 12, 24 and 36 months after transplantation; 9. Severity of fatigue using FSS at 12, 24 and 36 months after transplantation; 10. Safety (serious adverse events); 11. Tolerability of combination sirolimus and extended release tacrolimus (percentage of patients completing treatment and reasons for dose adjustments); 12. Percentage of patients on combination sirolimus and extended release tacrolimus converted to monotherapy extended release tacrolimus due to lack of tolerability or efficacy of combination sirolimus and extended release tacrolimus. | — |
Contacts
Public ContactH.J. Metselaar
's Gravendijkwal 230
Outcome results
None listed