Safety and Efficacy of the Early Introduction of Everolimus (Certican®) With Low Dose of Cyclosporine in de Novo Kidney Recipients After 1 Month of Transplantation

Calcineurin inhibitors, such as cyclosporine and tacrolimus, have improved allograft survival in kidney organ transplantation. Indeed, they have reduced the incidence of acute rejection episodes of cadaveric allograft recipients. Although marked progression has been made in initial survival rates, long-term kidney graft survival has yet to show such encouraging results. Because CNIs are associated with adverse effects, particularly nephrotoxicity, which contribute to declining organ function and eventual graft loss. In kidney transplants, progressive allograft dysfunction has been shown to develop in as many as 94% of patients by 1 year.

Therefore, reducing or eliminating the dose of CNIs to minimize nephrotoxicity must be balanced against the maintenance of adequate immunosuppression.

Certican allows CNI dose reduction then provides renal function improvement and current PSI strategy point out that early intervention is important in managing the risk of CAN before it develops in both de novo and maintenance renal transplant recipients.

To demonstrate Certican early introduction after 1 month provides better renal function with no change of efficacy compared to standard regimen, and also prevent delayed wound healing.

Study Overview

• Status: Completed
• Conditions: Planned Kidney Transplantation
• Intervention / Treatment: Drug: Everolimus + Low dose CsA +PD; Drug: Myfortic+ Standard CsA + PD

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Department of Surgery, Yonsei University College of Medicine, Severance Hospital

Participation Criteria

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:

1. Males or Females aged 18~65 years
2. De novo recipients of cadaveric, living unrelated or living related donor kidney transplants
3. Received kidney transplant from aged 10~65years donor
4. Willing to provide written informed consent
5. Completing study visits according to study protocol

Exclusion Criteria:

1. Recipients of multiple organ transplants
2. Kidney transplant from non-heart beating cadaveric donor / organ donor after cardiac death
3. Recipients of A-B-O incompatible transplants or lymphocyte cross-match positive transplants
4. Recipients of extra-renal solid organ transplants or stem cell transplants
5. Recipient/ donor who are known to have anti-HCV, HIV or HBsAg positive
6. Diagnosed as Cancer within the past 5 years (except complete recovered squamous cell or basal cell skin cancer)
7. Drug Hypersensitivity to investigational drugs or related drugs Females are pregnant and lactating

8. Any of the following laboratory abnormalities at screening:

   • ALT, AST, ALP, total bilirubin > 3 times the upper limit
   • ANC < 1,500mm3 or WBC < 2,500mm3 or platelet < 100,000 mm3
   • Cholesterol > 350 mg/dl or 9.0 mmol/L, TG > 500 mg/dl or 5.6mmol/L

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus + Low dose CsA +PD	Drug: Everolimus + Low dose CsA +PD; Group A : Initiation of 5mg/kg bid Neoral dose and 720mg bid Myfortic and then adjusting Neoral targeting 150-200ng. After 1 month reduce Neoral dose as following table and Certican starting 0.75mg bid then adjust Certican 3-8ng/ml. Myfortic continue until Certican trough level goes up >3 ng/mL. Steroid dose follows local protocol.
Active Comparator: Myfortic+ Standard CsA + PD	Drug: Myfortic+ Standard CsA + PD; Group B : Initiation of 5mg/kg bid Neoral dose and 720mg bid Myfortic and then adjusting Neoral targeting 150-200ng/ml. After 1 month reduce Neoral dose targeting 100-200ng with no change of Myfortic dose. Steroid dose follows local protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduced Exposure Cyclosporine in Renal Transplant Recipients	A 12-month, multi center, randomized, open-label, non-inferiority study of efficacy and safety comparing early introduction of Certican® after 1 month and standard regimen in de novo renal transplant recipients	12 months after the time of kidney transplantation

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Oh CK, Huh KH, Ha J, Kim YH, Kim YL, Kim YS. Safety and efficacy of the early introduction of everolimus with reduced-exposure cyclosporine a in de novo kidney recipients. Transplantation. 2015 Jan;99(1):180-6. doi: 10.1097/TP.0000000000000225.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: October 8, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Estimate): February 19, 2014
• Last Update Submitted That Met QC Criteria: February 17, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: verLowCNI
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Everolimus
• Other Study ID Numbers: 4-2009-0109

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No