NCT00538265

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started May 2005

Longer than P75 for phase_4

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2005

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

October 1, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 2, 2007

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2010

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2011

Completed
Last Updated

February 3, 2011

Status Verified

February 1, 2011

Enrollment Period

4.7 years

First QC Date

October 1, 2007

Last Update Submit

February 2, 2011

Conditions

Keywords

liver transplantation, hepatitis C virus, immunoprophylaxis

Outcome Measures

Primary Outcomes (1)

  • The primary endpoint will be degree of fibrosis = Ishak's histological score of hepatic biopsy at 1 year

    1 year

Secondary Outcomes (2)

  • • Ishak's degree of activity

    1 year

  • Ishak's degree of fibrosis

    2 years

Study Arms (3)

A

ACTIVE COMPARATOR

tacrolimus + steroids

Drug: tacrolimus

B

EXPERIMENTAL

ATG+ tacrolimus without steroids in maintenance therapy

Drug: tacrolimus, ATG

C

EXPERIMENTAL

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

Drug: ATG+mycophénolate mofétil+tacrolimus

Interventions

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

Also known as: PROGRAF
A

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)

Also known as: Thymoglobuline
B

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.

Also known as: Mycophénolate mofétil = Cellcept
C

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Hopital Pellegrin Tripode

Bordeaux, 33076, France

Location

La CONCEPTION hospital

Marseille, 13385, France

Location

Hopital Saint-Eloi

Montpellier, 34295, France

Location

Hopital de L'Archet

Nice, 06200, France

Location

Hôpital Cochin

Paris, 75000, France

Location

Hôpital Pontchaillou

Rennes, 35, France

Location

University Hospital

Toulouse, 31500, France

Location

Hopital Paul Brousse

Villejuif, 94804, France

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

TacrolimusAntilymphocyte Serum

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex Mixtures

Study Officials

  • Rostaing Lionel, PhD

    University Hospital, Toulouse

    PRINCIPAL INVESTIGATOR
  • Calmus Yvon, PhD

    UHCochin, Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

October 1, 2007

First Posted

October 2, 2007

Study Start

May 1, 2005

Primary Completion

January 1, 2010

Study Completion

January 1, 2011

Last Updated

February 3, 2011

Record last verified: 2011-02

Locations