Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program (Senator)

This study has been terminated.
(The study was terminated because the required sample size of 240-260 de novo senior renal transplant patients was not achieved within a reasonable time.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00956293
First received: August 7, 2009
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

This study wants to address whether a calcineurin-inhibitor (CNI)-free regimen six weeks after transplantation for Eurotransplant Senior Program (ESP) patients is as safe and well tolerated as standard treatment but optimizing immunosuppressive therapy with benefits in renal function, new-onset diabetes mellitus, cardiovascular risk, cancer and allograft nephropathy.


Condition Intervention Phase
Renal Transplantation
Drug: Basiliximab
Drug: Enteric Coated Mycophenolic Acid (MPA)
Drug: RAD001
Drug: Cyclosporin A (CsA)
Drug: Corticosteroids
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 6-month, Open-label, Randomized, Multicenter, Prospective, Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    The study was terminated prematurely and not powered for efficacy.


Secondary Outcome Measures:
  • Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    The study was terminated prematurely and not powered for efficacy.

  • Renal Function by Serum Creatinine [ Time Frame: Months 6, 12, 24, 36, 48 and 60 ] [ Designated as safety issue: No ]
    The study was terminated prematurely and not powered for efficacy.

  • Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death [ Time Frame: Months 6, 12, 24, 36, 48 and 60 ] [ Designated as safety issue: No ]
    The study was terminated prematurely and not powered for efficacy.

  • Occurrence of Treatment Failures [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    The study was terminated prematurely and not powered for efficacy.

  • Evolution of Renal Function (Creatinine Slope) [ Time Frame: Week 7, Month 6 ] [ Designated as safety issue: No ]
    The study was terminated prematurely and not powered for efficacy.

  • CD25 Saturation on Lymphocytes [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death [ Time Frame: Months 6, 12, 24, 36, 48 and 60 ] [ Designated as safety issue: Yes ]
    Participants with adverse events (serious plus non-serious), serious adverse events and death were reported.

  • Renal Function by GFR Over Time [ Time Frame: Months 12, 24, 36, 48 and 60 ] [ Designated as safety issue: No ]
  • Renal Function by Proteinuria [ Time Frame: Months12, 24, 36, 48 and 60 ] [ Designated as safety issue: No ]

Enrollment: 207
Study Start Date: July 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control group
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
Drug: Basiliximab
On day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group.
Other Name: Simulect
Drug: Enteric Coated Mycophenolic Acid (MPA)
A loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible.
Other Name: Myfortic
Drug: Cyclosporin A (CsA)
Dosage was based according to blood level
Other Name: Sandimmun Optoral
Drug: Corticosteroids
Dosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization).
Experimental: Everolimus group
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
Drug: Basiliximab
On day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group.
Other Name: Simulect
Drug: Enteric Coated Mycophenolic Acid (MPA)
A loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible.
Other Name: Myfortic
Drug: RAD001
Upon randomization, 3 mg (od) on Day 1, and 3 mg (1.5 mg every 12 hours) on Day 2 was given. Afterwards, the dosage was based on blood trough level (5 - 10 ng/mL).
Other Name: RAD001, Certcian
Drug: Cyclosporin A (CsA)
Dosage was based according to blood level
Other Name: Sandimmun Optoral
Drug: Corticosteroids
Dosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization).

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients receiving a primary kidney from a donor aged > 65 years
  • In the Eurotransplant Senior Program
  • Recipients of de novo cadaveric kidney transplants

Exclusion criteria:

  • Multi-organ recipients (e.g., kidney and pancreas)
  • Patients receiving a kidney from a non-heart beating donor
  • Patients who are recipients of A-B-O incompatible transplants
  • Patients with already existing antibodies against the HLA-type of the receiving transplant
  • Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1)
  • Patients with thrombocytopenia, with an absolute neutrophil count of < 1,500/mm³ or leucopenia or hemoglobin < 6 g/dL
  • Patients who are HIV, HCV RNA, or Hepatitis B surface antigen positive
  • Evidence of severe liver disease
  • Females at randomization who will be not considered post-menopausal

Other protocol-defined inclusion/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: NCT00956293

Locations
Germany
Novartis Investigative Site
Aachen, Germany, 52074
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Duesseldorf, Germany, 40225
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Kaiserslautern, Germany, 67655
Novartis Investigative Site
Koeln-Merheim, Germany, 51109
Novartis Investigative Site
München, Germany, 81377
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00956293     History of Changes
Other Study ID Numbers: CRAD001ADE19, EudraCT-NO. 2008-005109-20, 2008-005109-20
Study First Received: August 7, 2009
Results First Received: March 26, 2014
Last Updated: May 23, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

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

ClinicalTrials.gov processed this record on October 19, 2014