Cardiovascular Risk Following Conversion to Full Dose Myfortic® and Neoral® Two-hour Post Level Monitoring (COBACAM)

January 5, 2017 updated by: AShoker, University of Saskatchewan

Comparisons Of Inflammatory Biomarkers And Cardiovascular Risk Scores Before And After Conversion To Full Dose Myfortic® Using Two Hour Neoral® Monitoring.

The overall goal of this study is to improve cardiovascular outcomes in transplant recipients. The current standard immunosuppressive regimen in kidney transplant recipients depends on a higher exposure to the Calcineurin Inhibitor (CNI), and often a less than optimal dosage the of mycophenolic acid (MPA) derivative. The premise of this study is to investigate the effects of reversing this paradigm. More specifically, the effect of using maximum MPA dosages (in the form of enteric-coated mycophenolate sodium [EC-MPS] or Myfortic®) along with judicious CNI exposure (cyclosporine/Neoral®) will be investigated.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Research Question:

Will treating kidney transplant recipients with maximum MPA dosages (in the form of EC-MPS or Myfortic®) along with judicious CNI exposure (cyclosporine/Neoral®) lead to improved cardiovascular outcomes, as measured by the Framingham Risk Score, 7-year major adverse cardiac events (MACE) score and cardiovascular risk inflammatory biomarker profile?

Primary Objectives:

  1. To improve the Framingham Risk Score and 7-year MACE score for renal transplant recipients, which estimate risk for cardiovascular disease.
  2. To improve the cardiovascular risk inflammatory biomarker profile.

Hypothesis:

The more consistent drug exposure and lower Cmax noted with monitoring cyclosporine using the 2h levels (C2) combined with full dose Myfortic® will decrease Framingham Risk Score, MACE score, as well as markers of inflammation in kidney transplant recipients because:

  1. CNI minimization protocols are widely accepted as a strategy to ameliorate allograft and vascular injury.
  2. Chronic allograft injury and vascular disease are known inflammatory conditions.
  3. The MPA derivatives possess significant anti-inflammatory properties.

Study Type

Interventional

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

  • Canada
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4R 3C2
        • Kidney Health Center
      • Saskatoon, Saskatchewan, Canada, S7M 0Z9
        • St. Paul's Hospital

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 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Kidney transplant patients followed as outpatients who are currently stabilized on immunosuppressive therapy with an MPA derivative, a CNI and prednisone where stability is defined as change in serum creatinine of less than 10% or over the last three months.
  2. Age 18-74 years old.
  3. At least six months after transplantation.
  4. Lack of transplant rejection within the last 12 weeks.
  5. Serum creatinine less than 300 umol/L at enrolment.
  6. Negative urine pregnancy test for female patients of childbearing potential.
  7. Consent to the study.
  8. Not included in another interventional clinical trial within the last 90 days.

Exclusion Criteria:

  1. Patients with other types of solid organ transplants.
  2. Patients with any form of substance abuse or major psychiatric disorder.
  3. Patients with acute or chronic diarrhea, known bowel disease or known gastroparesis.
  4. Patients receiving anti-lymphocyte treatment for rejection within the last six months.
  5. Patients not receiving a mycophenolic acid derivative.
  6. Patients who do not tolerate the maximum Myfortic® total daily dose of 1440 mg OD.
  7. Patients with significant liver disease defined as having an elevated bilirubin by at least two times the upper value of the normal range.
  8. Patients who have any unstable medical condition that could interfere with the study.
  9. Patients with chronic viral infection with HIV, Hepatitis B & C.
  10. Presence of any acute illness requiring admission to the hospital for the last 4 weeks.
  11. Pregnancy.
  12. Significant cardiovascular event such as MI, stroke or TIA within the last 12 weeks or uncontrolled hypertension.
  13. Immunosuppressant changes within the last month.

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: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Group
Maximization of mycophenolicacid (MPA) derivative (to a total daily dosage of 1440mg of Myfortic®) and reduction of cyclosporine dosage (as defined by C2 monitoring) in 50 stable renal transplant patients previously on immunosuppressive therapy with cyclosporine, an MPA derivative and prednisone.
Drug: Myfortic®
Other Names:
  • mycophenolate sodium
  • MPA derivative
Drug: Neoral®
Other Names:
  • cyclosporine
Active Comparator: Control Group
25 patients continued on an mycophenolicacid (MPA) derivative, cyclosporine and prednisone.
Drug: Prednisone
Drug: Myfortic®
Other Names:
  • mycophenolate sodium
  • MPA derivative
Drug: Cellcept®
No Intervention: Observation Group
25 patients continued on an mycophenolic acid (MPA) derivative, tacrolimus, and prednisone will be followed during the same recruitment period as an additional comparison, as this is the other Calcineurin Inhibitor (CNI), which is used in kidney transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Framingham score for renal transplant recipients.
Time Frame: 1 year
Cardiovascular risk factors using the Framingham 2009 risk score for renal transplant recipients and at end of the one year.
1 year
Surrogate markers for potential biological differences between the groups.
Time Frame: 1 year

Cardiovascular (CV) Biomarkers compared between each group. CV Biomarkers of interest in this study include:

  1. Chemokines (including ccl 1, 2, 15 and Clx 9 and 10)
  2. Thrombopoitin
  3. Cytokines IL 1, 2, 4, 6, 10, TGF, INF.

These mediators are known to play a pivital role in atherosclerosis and progressive kidney failure.
1 year
Safety Measures
Time Frame: 1 year
Safety will be measured by estimated Glomerular filtration rate (GFR).
1 year
Change in 7-year MACE score for renal transplant recipients.
Time Frame: 1 year
Cardiovascular risk factors using the 7-year MACE calculator for renal transplant recipients and at end of the one year.
1 year

Collaborators and Investigators

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

Sponsor

University of Saskatchewan

Investigators

  • Principal Investigator: Ahmed Shoker, MD, University of Saskatchewan

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

February 1, 2014

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

January 15, 2014

First Submitted That Met QC Criteria

February 6, 2014

First Posted (Estimate)

February 10, 2014

Study Record Updates

Last Update Posted (Estimate)

January 9, 2017

Last Update Submitted That Met QC Criteria

January 5, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CERL080ACA15T

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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