A Study of CellCept (Mycophenolate Mofetil) Combined With Tacrolimus and Corticosteroids in Kidney Transplant Patients.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00758602
First received: September 24, 2008
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

This 2 arm study will compare the efficacy and safety of CellCept, combined with low or standard dose tacrolimus plus corticosteroids, in patients with kidney transplants. Patients will be randomized into one of 2 groups to receive either 1)CellCept 2.0g/day po bid + tacrolimus 10-12ng/mL followed by a maintenance dose of 8-10ng/mL + corticosteroids or 2)CellCept 2.0g/day po bid + tacrolimus 8-10ng/mL in the first 2 months,3-7ng/mL in month 3 followed by a maintenance dose of 3-5ng/mL + corticosteroids. The anticipated time on study treatment is 1 year, and the target sample size is 100-500 individuals.


Condition Intervention Phase
Kidney Transplantation
Drug: mycophenolate mofetil
Drug: tacrolimus, standard dose
Drug: tacrolimus, low dose
Drug: corticosteroids
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Study Comparing the Effect of CellCept Combined With Low Dose Versus Standard Dose Tacrolimus, and Corticosteroids, on Kidney Function in Renal Transplantation Patients

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Chronic Allograft Damage Index (CADI) Score at Month 12 After Transplantation [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    CADI scoring was defined for 6 histological categories: interstitial inflammatory cell infiltration (0 equals (=) no or mild inflammation, 1=approximately (~)25 percent (%) cell infiltration, 2=26-50% cell infiltration, and 3=greater than (>)50% cell infiltration); interstitial fibrosis (0=none, 1=~25% interstitial affected, 2=26-50% interstitial affected, and 3=>50% interstitial affected); tubular atrophy (0=none, 1=~15% proximal tubular atrophy [PTA], 2=16-30% PTA, and 3=>30% PTA); mesangial matrix proliferation (MMP; 0=none, 1=25% non-glomerulosclerosis [NGS] combined with moderate MMP, 2=25-50% NGS combined with MMP, and 3=>50% NGS combined with MMP); glomerular sclerosis (0=none, 1=~15% glomerulus affected, 2=16-50% glomerulus affected, and 3=>50% glomerulus affected); endothelial proliferation (EP; 0=none, 1=EP to less than (<)25% remaining artery/small artery membrane [RA/SAM], 2=EP to 26-50% [RA/SAM], and 3=>50% [RA/SAM]). CADI score was the sum of the 6 histological findings.

  • Glomerular Filtration Rate (GFR) at Month 12 After Transplantation [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    GFR was determined using the Cockcroft-Gault formula to calculate the creatinine clearance, at Month 12 after renal transplantation. For males, creatinine clearance [milliliters per minute (mL/min)] = [(140 minus age) multiplied by (*) (body weight in kg) divided by [72 * serum creatinine mg per deciliter (mg/dL)]. For females, creatinine clearance (mL/min) = 0.85 * [(140 minus age) * (body weight in kg)] divided by [72 * serum creatinine (mg/dL)].


Secondary Outcome Measures:
  • Percentage of Participants Experiencing Acute Rejection, Graft Loss, or Death at 6 and 12 Months Post-Transplant [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: No ]
  • Time to First Acute Rejection Post-Transplant - Number of Participants With an Event [ Time Frame: BL, Weeks 2, 4, 13, 26, 39, and 52 ] [ Designated as safety issue: No ]
  • Time to First Acute Rejection Post-Transplant [ Time Frame: BL, Weeks 2, 4, 13, 26, 39, and 52 ] [ Designated as safety issue: No ]
    The median time, in days, between randomization and acute rejection.

  • Percentage of Participants With Treatment Failure at 12 Months Post-Transplant [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Treatment failure was defined by the occurrence of any of the following: use of additional maintenance immunosuppressive medication not specified in the assigned treatment group; discontinuation of any of the assigned immunosuppressants for more than 14 consecutive days or 30 cumulative days; graft loss or return to chronic dialysis; or death.

  • Participant and Graft Survival [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: No ]
    The percentage of participants surviving with grafts intact at 6 and 12 months after renal transplant.

  • Serum Creatinine (Micromoles Per Liter [µmol/L]) [ Time Frame: BL, Weeks 2, 4, 13, 26, 39, and 52 ] [ Designated as safety issue: No ]
    The mean serum creatinine values in µmol/L at Baseline (BL), Weeks 2, 4, 13, 26, 39, and 52.

  • Glomerular Filtration Rate (GFR) (mL/Min) [ Time Frame: BL, Weeks 2, 4, 13, 26, 39, and 52 ] [ Designated as safety issue: No ]
    The mean GFR values in mL/min at BL, Weeks 2, 4, 13, 26, 39, and 52.


Enrollment: 210
Study Start Date: September 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MMF, Standard Dose Tacrolimus
Participants received mycophenolate mofetil (MMF) 0.75 to (-) 1 gram (g), orally (PO), twice daily (BID) from Day 0 through Month 12. Participants also received tacrolimus 0.1-0.15 milligrams per kilogram (mg/kg), PO, BID to reach a target trough dose of 8-10 nanograms per milliliter (ng/mL) from Day 0 through Month 3; the dose was adjusted to reach a target trough level of 7-10 ng/mL in Month 3 and continued through Month 12. Participants also received corticosteroids per center practice.
Drug: mycophenolate mofetil
0.75-1 g PO BID from Day 0 through Month 12
Other Name: CellCept
Drug: tacrolimus, standard dose
Initial dose of 0.1-0.15 mg/kg PO BID to reach a target trough dose of 8-10 ng/mL from Day 0 through Month 3; the dose was adjusted to reach a target trough level of 7-10 ng/mL in Month 3 and continued through Month 12.
Drug: corticosteroids
According to center's practice
Experimental: MMF, Low Dose Tacrolimus
Participants received MMF 0.75-1 g, PO, BID from Day 0 through Month 12. Participants also received tacrolimus 0.1-0.15 mg/kg, PO, BID to reach a target trough dose of 8-10 ng/mL from Day 0 through Month 3; the dose was adjusted to 0.05-0.08 mg/kg, PO, BID to reach a target trough dose of 2-5 ng/mL in Month 3 and continued through Month 12. Participants also received corticosteroids per center practice.
Drug: mycophenolate mofetil
0.75-1 g PO BID from Day 0 through Month 12
Other Name: CellCept
Drug: tacrolimus, low dose
Initial dose of 0.1-0.15 mg/kg PO BID to reach a target trough dose of 8 to 10 ng/mL from Day 0 through Month 3; 0.05-0.08 mg/kg PO BID to reach a target trough dose of 2-5 ng/mL in Month 3 and continued through Month 12.
Drug: corticosteroids
According to center's practice

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, <=75 years of age;
  • single organ recipients of renal allograft;
  • negative pregnancy test for women of childbearing potential; reliable contraception must be used before starting drug therapy, until 6 weeks after the last dose of study medication.

Exclusion Criteria:

  • severe gastrointestinal disease which may influence the absorption of oral drug therapy;
  • severe infection, HIV or active hepatitis;
  • active gastric ulcers;
  • malignancy other than cured skin cancer;
  • severe anemia, leucopenia or thrombocytopenia.
  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: NCT00758602

Locations
China
Beijing, China, 100020
Fuzhou, China, 350025
Guangzhou, China, 510080
Nanjing, China, 210008
Shanghai, China, 200025
Zhejiang, China, 310003
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00758602     History of Changes
Other Study ID Numbers: ML21740
Study First Received: September 24, 2008
Results First Received: July 8, 2014
Last Updated: July 8, 2014
Health Authority: China: State Fodd and Drug Administration

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014