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An open-label randomized multicenter clinical study comparing three regimes of immunosuppression : (A) tacrolimus and steroids, (B) antithymocyte induction therapy and full dose of tacrolimus, (C) antithymocyte induction therapy with mycophenolate mofetil and a reduced dose of tacrolimus.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Active Comparator | tacrolimus + steroids |
|
| B | Experimental | ATG+ tacrolimus without steroids in maintenance therapy |
|
| C | Experimental | ATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tacrolimus | Drug | Tacrolimus started at 0.50 mg/kg b.i.d. starting at D0, by nasogastric tube and then 1 to 2 hours before meals. The dose of tacrolimus will be adjusted as soon as possible to obtain trough concentrations of the product between 10 and 20 µg/L between D0 and 6 months and then between 8 and 15 µg/L after 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| • Ishak's degree of activity | 1 year | |
| Ishak's degree of fibrosis | 2 years |
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Inclusion Criteria:
Exclusion Criteria:
• Preoperative serious renal impairment (serum creatinine levels > 200 µmol/l),
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| Name | Affiliation | Role |
|---|---|---|
| Rostaing Lionel, PhD | University Hospital, Toulouse | Principal Investigator |
| Calmus Yvon, PhD | UHCochin, Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Pellegrin Tripode | Bordeaux | 33076 | France | |||
| La CONCEPTION hospital |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D000961 | Antilymphocyte Serum |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D007106 | Immune Sera |
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|
|
| tacrolimus, ATG | Drug | immunoprophylaxis allowing sparing of steroids in maintenance therapy combining induction therapy with 3 injections of antithymocyte globulins (ATG) (1.5 mg/kg/d at D0, D2 and D4) and tacrolimus at usual dosage. In this group of patients, the first injection of ATG will be infused over a period of at least 6 hours and will be started as soon as vascular anastomosis has been completed. It will be preceded by an injection of 3 mg/kg/d methylprednisolone. The second injection of ATG at D2, post transplantation will also be infused over 6 hours and will be preceded by an injection of 1 mg/kg methylprednisolone, and then subsequently steroids will be excluded from the treatment. The third and last injection at D4 post transplantation will be administered over a 6-hour period but will not be preceded by steroids. In this study arm, tacrolimus will be administered as in arm (A) |
|
|
| ATG+mycophénolate mofétil+tacrolimus | Drug | immunoprophylaxis allowing sparing of steroids in maintenance therapy combined with mycophenolate mofetil, at an initial dosage of 2 grams a day, and then adjusted to safety and tolerability in such a way so as to maintain PMN ≥ 750/mm3, and platelet counts ≥ 30000/mm3. In this study arm, the patients will receive the same doses of ATG and steroids (and according to the same methods) as in arm B. Tacrolimus started at 0.05 mg/kg b.i.d. starting at D0 by nasogastric tube and then 1 to 2 hours before meals. In this study arm, the tacrolimus dose will be reduced: targeted trough concentrations will be between 7 and 12 µg/L between D0 and 6 months and then between 3 et 7 µg/L after 6 months. |
|
|
| Marseille |
| 13385 |
| France |
| Hopital Saint-Eloi | Montpellier | 34295 | France |
| Hopital de L'Archet | Nice | 06200 | France |
| Hôpital Cochin | Paris | 75000 | France |
| Hôpital Pontchaillou | Rennes | 35 | France |
| University Hospital | Toulouse | 31500 | France |
| Hopital Paul Brousse | Villejuif | 94804 | France |
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D000906 |
| Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |