Benefit of Immunoprophylaxis on Fibrosis to Reduce Viral Load After Liver Transplantation

NCT ID: NCT00538265

Last Updated: 2011-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2011-01-31

Brief Summary

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.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

tacrolimus + steroids

Group Type: ACTIVE_COMPARATOR

tacrolimus

Intervention Type: 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

B

ATG+ tacrolimus without steroids in maintenance therapy

Group Type: EXPERIMENTAL

tacrolimus, ATG

Intervention Type: 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)

C

ATG+ Mycophenolate Mofetil + tacrolimus a reduced dosage without steroids in maintenance therapy

Group Type: EXPERIMENTAL

ATG+mycophénolate mofétil+tacrolimus

Intervention Type: 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.

Interventions

tacrolimus

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

Intervention Type: DRUG

tacrolimus, ATG

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)

Intervention Type: DRUG

ATG+mycophénolate mofétil+tacrolimus

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.

Intervention Type: DRUG

Other Intervention Names

PROGRAF; Thymoglobuline; Mycophénolate mofétil = Cellcept

Eligibility Criteria

Inclusion Criteria

• patients who received a first liver transplantation,
• presenting with a qualitative or quantitative PCR positive for hepatitis C virus at time of transplantation, whatever the transaminase activity,
• Women of childbearing potential with a negative pregnancy test,
• Male or female patients who agree to use an effective method of contraception,
• patients who signed a written informed consent form to participate in the study,
• patients who are compliant and likely to follow the visits specified by the study protocol

Exclusion Criteria

• • Preoperative serious renal impairment (serum creatinine levels > 200 µmol/l),

• repeat transplantation,
• multiple organ transplantation,
• transplantation performed with an organ transplant obtained from a living donor or a reduced or shared organ grafts,
• serious concomitant disorder,
• positive serology for HBs antigen or HIV positive at time of enrollment,
• previous history of nonhepatic cancer (except for localized skin cancer),
• presence of a hepatocellular carcinoma, for which the primary lesion exceeds 5 cm or is complicated by portal thrombosis or metastatic disease,
• an investigational product or therapy administered less than one month before entry into the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

University Hospital Toulouse

Principal Investigators

Rostaing Lionel, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Calmus Yvon, PhD

Role: PRINCIPAL_INVESTIGATOR

UHCochin, Paris

Locations

Hopital Pellegrin Tripode

Bordeaux, , France

La CONCEPTION hospital

Marseille, , France

Hopital Saint-Eloi

Montpellier, , France

Hopital de L'Archet

Nice, , France

Hôpital Cochin

Paris, , France

Hôpital Pontchaillou

Rennes, , France

University Hospital

Toulouse, , France

Hopital Paul Brousse

Villejuif, , France

Countries

France

Other Identifiers

0404003

Identifier Type: -

Identifier Source: org_study_id