A Twelve-month, Multicenter, Open-label, Randomized Study of the Safety, Tolerability and Efficacy of Everolimus With Basiliximab, Corticosteroids and Two Different Exposure Levels of Tacrolimus in de Novo Renal Transplant Recipients

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00369161
First received: August 25, 2006
Last updated: March 25, 2011
Last verified: March 2011
  Purpose

This study is designed to evaluate whether tacrolimus dose reduction in de novo renal recipients receiving everolimus can preserve renal function while maintaining efficacy.


Condition Intervention Phase
Renal Transplantation
Drug: Everolimus (RAD001)
Drug: Tacrolimus
Drug: Basiliximab
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: Prevention
Official Title: A Twelve-month, Multicenter, Open-label, Randomized Study of the Safety, Tolerability and Efficacy of Everolimus With IL-2 Receptor Antagonist, Corticosteroids and Two Different Exposure Levels of Tacrolimus in de Novo Renal Transplant Recipients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Renal Function Assessed by Calculated Glomerular Filtration Rate (cGFR) [ Time Frame: 12 months post -transplant ] [ Designated as safety issue: No ]

    Renal function was assessed by calculated glomerular filtration rate (cGFR) using Modification of Diet in Renal Disease (MDRD)formula.

    GFR [mL/min/1.73m^2] = 186.3*(C-1.154)*(A-0.203)*G*R, where:

    • C is the serum concentration of creatinine [mg/dL],
    • A is patient age at sample collection date [years],
    • G=0.742 when gender is female, otherwise G=1,
    • R=1.21 when race is black, otherwise R=1


Secondary Outcome Measures:
  • Number of Participants With Incidence of Biopsy-proven Acute Rejection (BPAR) [ Time Frame: from Month 4 through to Month 12 ] [ Designated as safety issue: No ]
    Biopsy-proven acute rejection (BPAR) was defined as a clinically suspected acute rejection confirmed by biopsy (performed by the local pathologist). For all clinically suspected rejection episodes a graft core biopsy must have been performed before or within a 24 hour period from the initiation of anti-rejection therapy.

  • Percentage of Participants With Efficacy Failure [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Efficacy failure was a composite of BPAR, graft loss, death or lost to follow-up. BPAR was defined as a clinically suspected acute rejection confirmed by biopsy (performed by the local pathologist). For all clinically suspected rejection episodes a graft core biopsy must have been performed before or within a 24 hour period from the initiation of anti-rejection therapy. An allograft was presumed to be lost on the day a patient started dialysis and was unable to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, the day of nephrectomy was the day of graft loss.


Enrollment: 228
Study Start Date: June 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Very low dose tacrolimus
The first dose of everolimus was to be administered not later than 24 hours after transplantation with a starting dose of 1.5 mg bis in diem/twice a day (b.i.d.) thereafter adjusted to maintain the trough blood levels between 3 and 8 ng/ml. Tacrolimus was to be initiated within 24 hours after reperfusion of the graft with a starting dose of 0.1 mg/kg/day thereafter adjusted to maintain the trough blood levels between 4 and 7 ng/ml. Up to months three all patients received the same treatment and after three months patients in this arm received tacrolimus to reach a trough blood level between 1.5 and 3 ng/ml. All patients received two doses of 20 mg basiliximab, administered as an intravenous bolus injection. The first dose was given on the day of transplantation, with the second dose being administered on the fourth day post-transplant. Intravenous (i.v.) prednisone (or equivalent) was given pre- or intra-operatively according to center practice.
Drug: Everolimus (RAD001) Drug: Tacrolimus Drug: Basiliximab Drug: Corticosteroids
Active Comparator: Low dose tacrolimus
The first dose of everolimus was to be administered not later than 24 hours after transplantation with a starting dose of 1.5 mg bis in diem/twice a day (b.i.d.) thereafter adjusted to maintain the trough blood levels between 3 and 8 ng/ml. Tacrolimus was to be initiated within 24 hours after reperfusion of the graft with a starting dose of 0.1 mg/kg/day thereafter adjusted to maintain the trough blood levels between 4 and 7 ng/ml. Up to months three all patients received the same treatment and after three months patients in this arm received tacrolimus to reach a trough blood level between 4 and 7 ng/ml. All patients received two doses of 20 mg basiliximab, administered as an intravenous bolus injection. The first dose was given on the day of transplantation, with the second dose being administered on the fourth day post-transplant. Intravenous (i.v.) prednisone (or equivalent) was given pre- or intra-operatively according to center practice.
Drug: Everolimus (RAD001) Drug: Tacrolimus Drug: Basiliximab Drug: Corticosteroids

  Eligibility

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

Inclusion criteria

  • Male or female of 18-65 years old
  • Patient who has received a primary kidney transplant from a cadaveric, living unrelated or non-human leucocyte antigen (HLA) identical living related donor
  • Recipient of a kidney with a cold ischemia time (CIT) < 30 hours
  • Recipient of a kidney from a donor 10-65 years old
  • Patient able to receive the first dose of tacrolimus within 24 hours from graft reperfusion
  • Female capable of becoming pregnant must have a negative pregnancy test and is required to practice a medically approved method of birth control for the duration of the study and for a period of three months following discontinuation of investigational drug
  • Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months

Exclusion criteria

  • Patient who has previously received an organ transplant
  • Recipient of multiple organ transplants
  • Recipient of a kidney transplant from a non heart-beating donor
  • Recipient of donor specific transfusions
  • Recipient of A-B-O incompatible transplant or T-cell cross-match positive transplant
  • Patient with current Panel Reactive Antibodies (PRA) level ≥ 50%
  • Recipient of a kidney from a donor who tests positive for hepatitis B surface antigen or hepatitis C antibodies
  • Patient who is human immunodeficiency virus (HIV) positive
  • Patient who has a positive hepatitis C serology or who is hepatitis B surface antigen positive with evidence of liver injury as indicated by aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels ≥2.5 times upper limit of normal (UNL). Viral serology results obtained within 6 months prior to the administration of the first dose of Certican™ are acceptable
  • Patient with severe hypercholesterolemia (350 mg/dL, 9.1 mmoL/dL) or hypertriglyceridemia ( 500 mg/dL, 5.6 mmoL/L)
  • Patient with white blood cell (WBC) count 3,000/mm3 or with platelet count 75,000/mm3
  • Patient with any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or with hypersensitivity to drugs similar to Certican (e.g., macrolides)
  • Patient who has been treated with an immunosuppressive drug or an investigational drug within 4 weeks prior to the administration of the first dose of Certican
  • Patient with uncontrolled infection
  • Patient with any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment in this trial
  • Patient with a known malignancy or a history of malignancy within last 5 years other than successfully treated localized basal or squamous cell carcinoma of the skin
  • Abnormal physical or laboratory findings of clinical significance within 2 weeks prior to the administration of the first dose of Certican™ which at investigator's discretion would interfere with the objectives of the study
  • Breast feeding women
  • Patient with symptoms of significant somatic or mental illness or with unresolved history of drug or alcohol abuse
  • Patient unable to cooperate or communicate with the investigator
  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: NCT00369161

Locations
Switzerland
Novartis
Basel, 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: External Affairs, Novartis Pharmaceticals
ClinicalTrials.gov Identifier: NCT00369161     History of Changes
Other Study ID Numbers: CRAD001A2426
Study First Received: August 25, 2006
Results First Received: December 17, 2010
Last Updated: March 25, 2011
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Additional relevant MeSH terms:
Everolimus
Sirolimus
Tacrolimus
Basiliximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 18, 2014