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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00154310
First received: September 8, 2005
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Renal Transplantation
Drug: Everolimus
Drug: Cyclosporine
Drug: Enteric-coated mycophenolate sodium
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: Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Everolimus in Comparison to Standard Therapy With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Cyclosporine Microemulsion in de Novo Renal Transplant Patients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Renal Function (Nankivell Formula) at Month 12 Post Transplantation. [ Time Frame: at Month 12 post transplantation ] [ Designated as safety issue: No ]
    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:
  • Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death [ Time Frame: Up to Month 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Occurrence of Treatment Failures [ Time Frame: up to or at Month 12 ] [ Designated as safety issue: No ]
    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).

  • Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12 [ Time Frame: Month 4.5 and Month 12 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Aes from end of core study period (month 12) to end of follow-up period (month 60) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 300
Study Start Date: June 2005
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + 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.
Drug: Everolimus
Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL.
Other Name: certican
Drug: Enteric-coated mycophenolate sodium
Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.
Other Name: Myfortic
Drug: Corticosteroids
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.
Active Comparator: Cyclosporine + 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.
Drug: Cyclosporine
Tablets orally twice a day to maintain protocol specific target blood levels
Other Name: Sandimmun Optoral
Drug: Enteric-coated mycophenolate sodium
Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.
Other Name: Myfortic
Drug: Corticosteroids
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria :

The following inclusion criteria had to be present at BL 1 (Screening visit prior to transplantation):

  1. Males or females, aged 18 - 65 years
  2. Recipients of de novo cadaveric, living unrelated or living related kidney transplants
  3. Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at BL 1, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility
  4. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained

    Of all patients included into the study at BL 1 (prior to transplantation), those who continued into the randomized study period had to meet the following condition at BL 2, prior to randomization:

  5. Patients had to be on an immunosuppressive regimen with EC-MPS (target dose; 1440 mg/day, if tolerated; minimal dose: 720 mg/day), cyclosporine and corticosteroids
  6. Patients with an actual serum creatinine =< 3.0 mg/dl

Exclusion Criteria:

The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):

  1. More than one previous renal transplantation
  2. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
  3. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
  4. Patients who are recipients of A-B-O incompatible transplants
  5. Patients with a historical or current peak PRA of > 25%
  6. Patients with already existing antibodies against the HLA-type of the receiving transplant
  7. 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:

  8. Graft loss or death
  9. Changes to the immunosuppressive regimen prior to randomization due to immunologic reasons
  10. Patients who suffered from severe rejection (>= BANFF II acute rejection), recurrent acute rejection, or steroid resistant acute rejection
  11. Proteinuria > 1g/day

Other protocol-defined 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: NCT00154310

Locations
Germany
Novartis Investigational Sites
Nurnberg, Germany
Switzerland
Novartis Pharma AG
Basel, Switzerland
Novartis Investigational Sites
Bern, Switzerland
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Novartis
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00154310     History of Changes
Other Study ID Numbers: CRAD001A2418
Study First Received: September 8, 2005
Results First Received: January 11, 2011
Last Updated: October 21, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Renal transplantation, everolimus, immunosuppressants, CNI-free

Additional relevant MeSH terms:
Everolimus
Sirolimus
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Immunosuppressive Agents
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 16, 2014