Everolimus in a Cyclosporine Microemulsion-free Regimen Compared to a Low-dose Cyclosporine Microemulsion Regimen, in de Novo Kidney Transplant Patients (CERTES02)

July 11, 2018 updated by: Novartis

A 12 Month, Multicenter, Randomized, Parallel, Open-label Study, to Evaluate Renal Function and Efficacy of Everolimus With Basiliximab and Cyclosporine Microemulsion Discontinuation at 3 Month Post-transplant Versus Minimization, in de Novo Kidney Transplant Recipients

The purpose of this study is to evaluate the safety and efficacy of everolimus in combination with basiliximab, and steroids with and without cyclosporine microemulsion in de novo kidney transplant recipients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a combined analysis using 81 patients randomized and treated in CRAD001A2419 (NCT00154284) with 33 randomized and treated in CRAD001A2423 (NCT00170807). This approach is reflected in the protocol amendments for each study, and the one clinical study report for both.

Study Type

Interventional

Enrollment (Actual)

114

Phase

  • Phase 3

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Recipients of a first renal transplant from a primary cadaveric or non-HLA identical living related donor.
  • Renal cold ischemic time < 36 hours.
  • Age of donor < 65 years.

Exclusion Criteria:

  • Patients who have received an investigational drug within 4 weeks of baseline period.
  • Patients who are recipients of multiple organ transplants, including any organ other than kidney.
  • Recipients of non-heart beating donor organs.

Other protocol-defined 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: Everolimus (Certican) with Cyclosporine (Neoral) Continuation
Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Drug: Everolimus (Certican)
Other Names:
  • Certican
Drug: Cyclosporine (Neoral)
Other Names:
  • Neoral
Drug: Steroid
Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Other Names:
  • Prednisone
Drug: Basiliximab (Simulect)
Other Names:
  • Simulect
Experimental: Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal
Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Drug: Everolimus (Certican)
Other Names:
  • Certican
Drug: Cyclosporine (Neoral)
Other Names:
  • Neoral
Drug: Steroid
Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Other Names:
  • Prednisone
Drug: Basiliximab (Simulect)
Other Names:
  • Simulect

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula)
Time Frame: At Month 3 and Month 12

Nankivell's formula for calculated GFR is shown below:

GFR [mL/min] = 6.7/C + W/4 - UREA/2 - 100/H2+ 35 (25 for females). Where W is body weight at specific visit [kg], H is height at specific visit [m], C is the serum concentration of creatinine [mmol/L], and UREA is the serum concentration of urea [mmol/L]. UREA was calculated from blood urea nitrogen (BUN) lab data by: UREA = 2.1441*BUN. If a GFR value from Nankivell formula was less than 10 [mL/min], then the value was assigned as 10 [mL/min].
At Month 3 and Month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up
Time Frame: Month 12
Renal biopsies were collected for all cases of suspected acute rejection. For these cases, regardless of initiation of anti-rejection treatment, a graft core biopsy had been performed within 48 hours. These biopsies were listed on the Kidney Allograft Biopsy eCRF and the results used for patient management for BPAR. Graft loss was defined as the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis as well as re-transplant. BPAR, graft loss, death, or loss to follow-up was analyzed by means of frequency tables.
Month 12
Serum Creatinine at Month 6 and 12
Time Frame: 6 month and 12 months
serum creatinine summarized by mean and standard deviation
6 month and 12 months
Calculated Creatinine Clearance at 6 Month and 12 Month
Time Frame: 6 month and 12 months

Creatinine clearance calculated by Cockcroft-Gault formula and summarized by mean, and standard deviation. Cockcroft-Gault formula to calculate Creatinine Clearance (CrCl[mL/min]) is shown below:

CrCl[mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit [kg], C is the serum concentration of creatinine [mg/dL], R = 1 if the patient is male and = 0.85 if female.
6 month and 12 months

Collaborators and Investigators

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

Sponsor

Novartis

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

  • Grinyo JM, Paul J, Novoa P, et al. (2010). Better renal function in renal-transplant recipients treated with everolimus plus cyclosporine elimination compared with cyclosporine minimisation, Am J Transplant; 10(Suppl 4): 503: Abstract 1636.

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, 2005

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

July 1, 2008

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

August 9, 2018

Last Update Submitted That Met QC Criteria

July 11, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001A2419
  • CRAD001A2423 (Other Identifier: Novartis Pharmaceuticals)

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.

Clinical Trials on Organ Transplantation, Renal Transplantation

Clinical Trials on Everolimus (Certican)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe