Evaluation of the Therapeutic Benefit of an Initial Intensified Dosing Regimen of Mycophenolate Sodium Versus a Standard Regimen in Renal Transplant Patients

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00419926
First received: January 8, 2007
Last updated: February 25, 2011
Last verified: February 2011
  Purpose

The purpose of this study is to determine if an initial intensified enteric-coated mycophenolate sodium (Myfortic) dosing regimen administered during the first six weeks post renal transplantation provides improved efficacy, with a similar safety profile, compared to a standard regimen of Myfortic.


Condition Intervention Phase
Kidney Transplantation
Drug: Enteric-coated mycophenolate sodium (Myfortic)
Drug: Cyclosporine (Neoral)
Drug: Prednisone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized, Multicenter, Parallel-group, Open-label Study to Evaluate the Therapeutic Benefit of an Initially Intensified Dosing Regimen of Mycophenolate Sodium Versus a Standard Dosing Regimen, in Combination With Cyclosporine and Corticosteroids in de Novo Renal Transplant Patients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection [BPAR], graft loss [GFL] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)

  • Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection [BPAR], graft loss [GFL] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)


Secondary Outcome Measures:
  • Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death [ Time Frame: 21 and 84 days ] [ Designated as safety issue: Yes ]
    The overall treatment differences of the number of participants with at least one occurrence of the composite event BPAR, GFL or death at study days 21 and 84 post-transplantation. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)

  • Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit [ Time Frame: at 21 days, 84 days and 180 days ] [ Designated as safety issue: No ]
    The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the GFR. Serum creatinine levels, age, sex and race were used to estimate the GFR levels in mL/min/1.73m^2.

  • Renal Function Assessed by Serum Creatinine at Each Visits [ Time Frame: at 21 days, 84 days and 180 days ] [ Designated as safety issue: No ]

Enrollment: 313
Study Start Date: December 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intensified Mycophenolate Sodium (Myfortic) dosing regimen
In patients randomized to the intensified Myfortic dosing regimen, the initial dose was 2-fold of the labeled dose (i.e. 2880 mg/day). The dosage was reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.
Drug: Enteric-coated mycophenolate sodium (Myfortic)
1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.
Drug: Cyclosporine (Neoral)
cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels
Drug: Prednisone
20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.
Active Comparator: Standard Mycophenolate Sodium (Myfortic) dosing regimen
In patients randomized to the standard Myfortic dosing regimen, the initial dose of 1440 mg/day had to be maintained throughout the whole study.
Drug: Enteric-coated mycophenolate sodium (Myfortic)
1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.
Drug: Cyclosporine (Neoral)
cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels
Drug: Prednisone
20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Criteria

Inclusion Criteria:

  • Males or females, 18 to 65 years old
  • First or second time kidney transplant patients
  • For females capable of becoming pregnant, negative pregnancy test prior to entry into trial and effective birth control during trial and 3 months after stopping trial medication

Exclusion Criteria:

  • Previous graft loss due to immunological reasons in the 1st year after the 1st transplant
  • Multi-organ recipients or previous transplant of another organ, different from the kidney
  • Recipients from a non-heart-beating donor
  • Known hypersensitivity to mycophenolic acid or cyclosporine
  • HIV positive or Hepatitis B surface antigen positive
  • History of malignancy (past 5 years)
  • Pregnancy or planned pregnancy, lactating, or unwillingness to use effective contraception.
  • Evidence of severe liver disease

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00419926

Locations
Switzerland
Novartis
Basel, Switzerland
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Novartis
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00419926     History of Changes
Other Study ID Numbers: CERL080A2419
Study First Received: January 8, 2007
Results First Received: December 14, 2010
Last Updated: February 25, 2011
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Novartis:
Renal, Kidney, Intensified, Enteric-coated mycophenolate sodium, Transplant

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Prednisone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on August 28, 2014