Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients
- Conditions
- Renal Transplantation
- Interventions
- Registration Number
- NCT00154310
- Lead Sponsor
- Novartis
- Brief Summary
The purpose of this study is to assess whether a calcineurin inhibitor (CNI)-free regimen with enteric-coated mycophenolate sodium (EC-MPS) and everolimus is as safe and well-tolerated as the standard regimen containing enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion, but results in better renal function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
Not provided
The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):
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More than one previous renal transplantation
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Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
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Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
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Patients who are recipients of A-B-O incompatible transplants
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Patients with a historical or current peak PRA of > 25%
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Patients with already existing antibodies against the HLA-type of the receiving transplant
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Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception
Of all patients included into the study at BL 1 (prior to transplantation), those who met one or more of the following criteria at BL 2, prior to randomization, should not continue into the randomized study period:
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Graft loss or death
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Changes to the immunosuppressive regimen prior to randomization due to immunologic reasons
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Patients who suffered from severe rejection (>= BANFF II acute rejection), recurrent acute rejection, or steroid resistant acute rejection
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Proteinuria > 1g/day
Other protocol-defined exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Everolimus + Mycophenolate sodium Corticosteroids Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine + Mycophenolate sodium Cyclosporine Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine + Mycophenolate sodium Enteric-coated mycophenolate sodium Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine + Mycophenolate sodium Corticosteroids Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. Everolimus + Mycophenolate sodium Enteric-coated mycophenolate sodium Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Everolimus + Mycophenolate sodium Everolimus Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.
- Primary Outcome Measures
Name Time Method Renal Function (Nankivell Formula) at Month 12 Post Transplantation. at Month 12 post transplantation Renal function at the end of the trial assessed as mean absolute values of the glomerular filtration rate (GFR) calculated by Nankivell formula 12 months after renal transplantation. The Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^2 + C ; where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. Estimated GFR is expressed in mL/min per 1.73m\^2.
- Secondary Outcome Measures
Name Time Method Number of Participants With Occurrence of Treatment Failures up to or at Month 12 Treatment failures defined as a composite endpoint of biopsy proven acute rejection, graft loss, death, loss to follow up and discontinuations due to lack of efficacy or toxicity, or conversion to another regimen (at least one condition must be present).
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death Up to Month 12 The number of participants with occurrence of biopsy proven acute rejection (BPAR), graft loss, or death up to Month 12 during the randomized treatment period. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III according to Banff 97 classification. A graft core biopsy was performed prior to 24 hours following initiation of graft rejection therapy. The allograft is presumed to be lost on the day the patient starts dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12 Month 4.5 and Month 12 An updated 1991 Framingham coronary prediction algorithm was used to estimate the total risk of developing coronary heart diseases (CHD) over the course of 10 years. Risk was calculated separately for male and females. To calculate risk, points were assigned for each of the following risk factors: age, levels of LDL cholesterol, HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus. The sum of the individual risk factor points gives a total point score, which ranges from -5 to 18 for men and -16 to 24 for women. Higher points indicate a higher risk for CHD.
Number of Participants Who Experienced an Adverse Event or Serious Adverse Event Aes from end of core study period (month 12) to end of follow-up period (month 60) Additional information about the number of participants who experienced Adverse Events (greater than 5%) or Serious Adverse Events can be found in the Adverse Event section.
Trial Locations
- Locations (2)
Novartis Pharma AG
🇨🇭Basel, Switzerland
Novartis Investigational Sites
🇨🇭Bern, Switzerland