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

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• 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 · Drug: tacrolimus, standard dose · Drug: corticosteroids

• 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 · Drug: tacrolimus, low dose · Drug: corticosteroids

Interventions

• Drugmycophenolate mofetil

  0.75-1 g PO BID from Day 0 through Month 12

  Also known as: CellCept

• Drugtacrolimus, 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.

• Drugtacrolimus, 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.

• Drugcorticosteroids

  According to center's practice

Primary outcomes

1. Chronic Allograft Damage Index (CADI) Score at Month 12 After Transplantation

   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.

   Time frame: Month 12

2. Glomerular Filtration Rate (GFR) at Month 12 After Transplantation

   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 \[72 \* serum creatinine (mg/dL)\].

   Time frame: Month 12

Secondary outcomes

1. Percentage of Participants Experiencing Acute Rejection, Graft Loss, or Death at 6 and 12 Months Post-Transplant

   Time frame: Months 6 and 12

2. Time to First Acute Rejection Post-Transplant - Number of Participants With an Event

   Time frame: BL, Weeks 2, 4, 13, 26, 39, and 52

3. Time to First Acute Rejection Post-Transplant

   The median time, in days, between randomization and acute rejection.

   Time frame: BL, Weeks 2, 4, 13, 26, 39, and 52

4. Percentage of Participants With Treatment Failure at 12 Months Post-Transplant

   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.

   Time frame: Month 12

5. Participant and Graft Survival

   The percentage of participants surviving with grafts intact at 6 and 12 months after renal transplant.

   Time frame: Months 6 and 12

6. Serum Creatinine (Micromoles Per Liter [µmol/L])

   The mean serum creatinine values in µmol/L at Baseline (BL), Weeks 2, 4, 13, 26, 39, and 52.

   Time frame: BL, Weeks 2, 4, 13, 26, 39, and 52

7. Glomerular Filtration Rate (GFR) (mL/Min)

   The mean GFR values in mL/min at BL, Weeks 2, 4, 13, 26, 39, and 52.

   Time frame: BL, Weeks 2, 4, 13, 26, 39, and 52

Baseline characteristics