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

May 23, 2014 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

207

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • 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
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Myfortic
Drug: Cyclosporin A (CsA)
Dosage was based according to blood level
Other Names:
  • 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 Names:
  • 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 Names:
  • Myfortic
Drug: Cyclosporin A (CsA)
Dosage was based according to blood level
Other Names:
  • 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).
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 Names:
  • RAD001, Certcian

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method
Time Frame: Month 6
The study was terminated prematurely and not powered for efficacy.
Month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method
Time Frame: Month 6
The study was terminated prematurely and not powered for efficacy.
Month 6
Renal Function by Serum Creatinine
Time Frame: Months 6, 12, 24, 36, 48 and 60
The study was terminated prematurely and not powered for efficacy.
Months 6, 12, 24, 36, 48 and 60
Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death
Time Frame: Months 6, 12, 24, 36, 48 and 60
The study was terminated prematurely and not powered for efficacy.
Months 6, 12, 24, 36, 48 and 60
Occurrence of Treatment Failures
Time Frame: Month 6
The study was terminated prematurely and not powered for efficacy.
Month 6
Evolution of Renal Function (Creatinine Slope)
Time Frame: Week 7, Month 6
The study was terminated prematurely and not powered for efficacy.
Week 7, Month 6
CD25 Saturation on Lymphocytes
Time Frame: Month 6
Month 6
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Time Frame: Months 6, 12, 24, 36, 48 and 60
Participants with adverse events (serious plus non-serious), serious adverse events and death were reported.
Months 6, 12, 24, 36, 48 and 60
Renal Function by GFR Over Time
Time Frame: Months 12, 24, 36, 48 and 60
Months 12, 24, 36, 48 and 60
Renal Function by Proteinuria
Time Frame: Months12, 24, 36, 48 and 60
Months12, 24, 36, 48 and 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

August 7, 2009

First Submitted That Met QC Criteria

August 10, 2009

First Posted (Estimate)

August 11, 2009

Study Record Updates

Last Update Posted (Estimate)

June 6, 2014

Last Update Submitted That Met QC Criteria

May 23, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001ADE19
  • EudraCT-NO. 2008-005109-20
  • 2008-005109-20

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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