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

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ClinicalTrials.gov Identifier: NCT02058875
Recruitment Status : Withdrawn (The study funder retracted their grant funding offer before contract signed.)
First Posted : February 10, 2014
Last Update Posted : January 9, 2017
Sponsor:
Information provided by (Responsible Party):
AShoker, University of Saskatchewan

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Cardiovascular Outcomes Kidney Transplant Recipients Kidney Transplantation Drug: Myfortic® Drug: Neoral® Drug: Cellcept® Drug: Prednisone Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparisons Of Inflammatory Biomarkers And Cardiovascular Risk Scores Before And After Conversion To Full Dose Myfortic® Using Two Hour Neoral® Monitoring.
Study Start Date : February 2014
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: cyclosporine
Active Comparator: Control Group
25 patients continued on an mycophenolicacid (MPA) derivative, cyclosporine and prednisone.
 Drug: Myfortic®
Other Names:
  • mycophenolate sodium
  • MPA derivative

Drug: Cellcept®
Drug: Prednisone
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


  3. Safety Measures [ Time Frame: 1 year ]
    Safety will be measured by estimated Glomerular filtration rate (GFR).

  4. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02058875


Locations
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Canada, Saskatchewan
Kidney Health Center
Regina, Saskatchewan, Canada, S4R 3C2
St. Paul's Hospital
Saskatoon, Saskatchewan, Canada, S7M 0Z9
Sponsors and Collaborators
University of Saskatchewan
Investigators
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Principal Investigator: Ahmed Shoker, MD University of Saskatchewan
More Information
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Publications:

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Responsible Party: AShoker, M.D., University of Saskatchewan
ClinicalTrials.gov Identifier: NCT02058875    
Other Study ID Numbers: CERL080ACA15T
First Posted: February 10, 2014    Key Record Dates
Last Update Posted: January 9, 2017
Last Verified: January 2017
Additional relevant MeSH terms:
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Cardiovascular Diseases
Cyclosporine
Mycophenolic Acid
Prednisone
Cyclosporins
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents