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A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.

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ClinicalTrials.gov Identifier: NCT00545402
Recruitment Status : Completed
First Posted : October 17, 2007
Results First Posted : July 14, 2014
Last Update Posted : July 14, 2014
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 16, 2007
First Posted Date  ICMJE October 17, 2007
Results First Submitted Date  ICMJE June 9, 2014
Results First Posted Date  ICMJE July 14, 2014
Last Update Posted Date July 14, 2014
Study Start Date  ICMJE November 2007
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2014)
Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment ]
Banff criteria required at least 2 of the 3 following features for a histopathological diagnosis of acute rejection: portal inflammation, bile duct inflammation, and venous endothelial inflammation. Each item was graded from 0 to 3 where 0 equals (=) mild, 2 = moderate, and 3 = severe. The sum of the 3 individual scores, from 0 to 9, corresponded to the Rejection Activity Index (RAI). If RAI = 0, 1, or 2, there was no evidence of rejection. If RAI = 3, there was borderline acute rejection. If RAI = 4 or 5, there was mild acute rejection. If RAI = 6 or 7, there was moderate acute rejection. If RAI = 8 or 9, there was severe acute rejection.
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2007)
Incidence of biopsy proven and treated acute rejection up to month 12.
Change History Complete list of historical versions of study NCT00545402 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2014)
  • Percentage of Participants With Graft Loss [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment. ]
    Graft survival was defined as the time between the randomization date and the graft loss date. Participants were censored at the date of last follow up, the date of last contact or premature withdrawal, and date of death.
  • Graft Survival [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment. ]
    The median time, in months, between randomization and graft loss event. Participants were censored at the date of last follow up, the date of last contact or premature withdrawal, and date of death.
  • Overall Survival (OS) at Month 12 - Percentage of Participants With an Event [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 ]
    OS was defined as the time between the date of randomization and death up to Month 12. Participants were censored at the date of last follow up and the date of last contact or premature withdrawal.
  • Overall Survival at Month 12 [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 ]
    The median time, in months, between randomization and OS event. Participants were censored at the date of last follow up and the date of last contact or premature withdrawal.
  • Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 ]
    The percentage of participants with biopsies of grafts evaluated by central review and scored according to Banff criteria at Month 12 post-transplant.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2007)
Efficacy: Evaluation of patients and grafts survival up to M12; histological evaluation of grafts at M12. Safety: cardiovascular outcomes and renal function at M12; AEs, laboratory parameters.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.
Official Title  ICMJE A Randomized, Open Label Study Comparing the Effect of CellCept With Therapeutic Drug Monitoring, Tacrolimus and a Corticosteroid-sparing Regimen Versus Fixed Dose CellCept, Tacrolimus and Corticosteroids Maintained up to 6 Months, on Acute Rejection and Safety in Liver Transplant Patients.
Brief Summary This 2 arm study will compare the efficacy and safety of two CellCept-containing treatment regimens in de novo liver transplant patients. Patients will be randomized into one of two groups, to receive either CellCept (at a starting dose of 3g/day po, adjusted according to exposure) standard dose tacrolimus and corticosteroids (10-15 mg/kg i.v. on day 0), or fixed dose CellCept 2g/day po, standard dose tacrolimus and corticosteroids (10-15mg/kg i.v. on day 0, then reducing from 20mg to 5mg over 6 months, and discontinuing after 6 months). The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Liver Transplantation
Intervention  ICMJE
  • Drug: Mycophenolate mofetil, adjusted dose
    3 g/d PO BID during meals from Day 0 to Day 4, followed by dose adjustment based on AUC using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12.
    Other Name: CellCept
  • Drug: Tacrolimus
    Target trough level of 8-2 ng/mL from Day 0 to Month 1, adjusted to a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12
  • Drug: Corticosteroids, IV
    10-15 mg/kg IV pre-operation on Day 0
    Other Name: Solu-Medrol
  • Drug: Mycophenolate mofetil, Standard dose
    2 g/d PO BID during meals from Day 0 to Month 12
    Other Name: CellCept
  • Drug: Corticosteroids, PO
    20 mg/d QDS from Day 0 through Month 1; 15 mg/day, TID from the end of Month 1 through Month 2; 10 mg/d BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.
    Other Name: Cortancyl
Study Arms  ICMJE
  • Experimental: MMF, Adjusted Dose; Tacrolimus; Corticosteroids
    Participants received mycophenolate mofetil (MMF) 3 grams per day (g/d), orally (PO), twice per day (BID) with meals from Day 0 to Day 4; the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12. Participants also received tacrolimus adjusted to a target trough level of 8 to (-) 12 nanograms per milliliter (ng/mL) from Day 0 to Month 1; the dose was adjusted to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 milligrams per kilogram (mg/kg), intravenously (IV), pre-operation on Day 0.
    Interventions:
    • Drug: Mycophenolate mofetil, adjusted dose
    • Drug: Tacrolimus
    • Drug: Corticosteroids, IV
  • Active Comparator: MMF, Standard Dose; Tacrolimus; Corticosteroids
    Participants received MMF 2 g/d, PO, BID with meals from Day 0 to Month 12. Participants also received tacrolimus adjusted to a target trough level of 8-12 ng/mL from Day 0 to Month 1; the dose was reduced to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 mg/kg, IV, pre-operation on Day 0; followed by 20 mg/d, PO, 4 times per day (QDS) from Day 0 through Month 1; 15 mg/d, PO, 3 times per day (TID) from the end of Month 1 through Month 2; 10 mg/d, PO, BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.
    Interventions:
    • Drug: Tacrolimus
    • Drug: Corticosteroids, IV
    • Drug: Mycophenolate mofetil, Standard dose
    • Drug: Corticosteroids, PO
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 9, 2014)
180
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • recipient of a first orthotopic liver transplant.

Exclusion Criteria:

  • history of organ transplants;
  • patient receiving a multi-organ transplant;
  • calculated creatinine clearance <=30mL/min before transplant;
  • leukocyte count < 2000/mm3 at randomization;
  • history of cancer within past 5 years, except for successfully treated basal cell or squamous cell cancer, or in situ cervical cancer;
  • pregnant or breast-feeding females, or females of childbearing age not using effective contraception.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00545402
Other Study ID Numbers  ICMJE ML21273
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP