Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| PHRC/01-01 | Other Identifier | Rennes University Hospital | |
| CIC0203/011 |
Not provided
Not provided
insufficient enrollment
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Ministry of Health, France | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The prevention of graft rejection after liver transplantation benefits nowadays from a variety of newly developed immunosuppressive agents. This allows more flexible and individualized immunoprophylaxis and gives an opportunity to reduce the long-term side effects (hypertension, renal failure, diabetes, etc.) of immunosuppression. The purpose of this study is to evaluate, in liver transplanted patients, if low doses of tacrolimus, given in combination with mycophenolate mofetil, can result in a lower rate of long-term side effects without increasing the rate of graft rejection.
Tacrolimus and mycophenolate mofetil are currently approved immunosuppressive agents for the prevention of acute and chronic rejection in liver transplantation. Adverse effects of tacrolimus are dose-dependent and appear early after the onset of treatment. To prevent side effects, we propose to combine reduced doses of tacrolimus with another immunosuppressant, i.e. mycophenolate mofetil, administered at usual doses. This study evaluates the interest of this combination and, subsequently, the pharmacokinetics of mycophenolate mofetil in this therapeutic context. Patients undergoing liver transplantation will be randomized to tacrolimus at normal doses or to the combination of tacrolimus at half doses and mycophenolate mofetil. A corticotherapy will be associated in both groups. The safety will be evaluated on the number of graft rejections between day 1 after transplantation and week 48; the onset of complications (hypertension, renal failure, diabetes, etc.) will allow to evaluate the efficacy of both treatment schedules.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MMF+FK | Experimental | Low doses of tacrolimus in association with mycophenolate mofetil |
|
| FK | Active Comparator | Full recommended doses of tacrolimus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mycophenolate mofetil | Drug | Mycophenolate mofetil is administered at a dose of 1,5 g x 2 / day for the 6 first weeks, then 1g x 2 / day until M12. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Onset of acute rejection (criterion evaluating the risk) | between Day 1 and Week 48 | |
| Onset of at least one complication (hypertension, renal failure, diabetes) requiring a specific treatment (criterion evaluating the benefit) | between Week 9 and Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Onset of hypertension, renal failure, diabetes, hypercholesterolemia, or of a serious adverse effect of mycophenolate mofetil | between Day 1 and Week 48 |
Not provided
Inclusion Criteria:
Non-Inclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Karim Boudjema, MD, PhD | Rennes University Hospital | Study Director |
| Eric Bellissant, MD, PhD | Rennes University Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service de Chirurgie Digestive - Hôpital de la Côte de Nacre | Caen | 14033 | France | |||
| Service d'Hépatogastroentérologie - Hôpital Beaujon |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9846530 | Background | Jain AB, Hamad I, Rakela J, Dodson F, Kramer D, Demetris J, McMichael J, Starzl TE, Fung JJ. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: an interim report. Transplantation. 1998 Nov 27;66(10):1395-8. doi: 10.1097/00007890-199811270-00024. | |
| 10083497 |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Tacrolimus | Drug | In arm 1: Tacrolimus is administered at half recommended dose: 0,040 mg/Kg x 2 , in order to maintain plasma levels between 6 and 10 ng/ml for the 6 first weeks, between 5 and 8 ng/ml from week 7 to M6 and between 4 and 6 ng/ml between M6 and M12. In arm 2: Tacrolimus is administered at the recommended dose: 0,075 mg/Kg x 2 , in order to maintain plasma levels between 12 and 20 ng/ml for the 6 first weeks, between 10 and 15 ng/ml from week 7 to week 12, between 8 and 12 ng/ml between M4 and M6 and between 6 and 10 ng/ml between M6 and M12. |
|
|
| Clichy |
| 92110 |
| France |
| Service d'Hépatogastroentérologie - Hôpital Henri Mondor | Créteil | 94010 | France |
| Chirurgie Générale et Digestive - Hôpital de La Croix Rousse | Lyon | 69317 | France |
| Service d'Hépaogastroentérologie - Hôpital Saint Eloi | Montpellier | France |
| Service de Chirurgie Générale - Hôpital Cochin | Paris | 75679 | France |
| Département de Chirurgie Viscérale - Hôpital Pontchaillou | Rennes | 35033 | France |
| Centre Hépato-biliaire - Hôpital Paul Brousse | Villejuif | France |
| Klupp J, Glanemann M, Bechstein WO, Platz KP, Langrehr JM, Keck H, Settmacher U, Radtke C, Neuhaus R, Neuhaus P. Mycophenolate mofetil in combination with tacrolimus versus Neoral after liver transplantation. Transplant Proc. 1999 Feb-Mar;31(1-2):1113-4. doi: 10.1016/s0041-1345(98)01925-3. No abstract available. |
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D018942 | Macrolides |
| D007783 | Lactones |