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

Sponsor

University of Saskatchewan (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02058875

Collaborator

(none)

Enrollment

Locations

Arms

19.9

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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:

To improve the Framingham Risk Score and 7-year MACE score for renal transplant recipients, which estimate risk for cardiovascular disease.
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:

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

Study Design

Study Type:

Interventional

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 :

Feb 1, 2014

Actual Primary Completion Date :

Oct 1, 2015

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

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: 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.

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: 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

Primary Outcome Measures

Change in Framingham score for renal transplant recipients. [1 year]
Cardiovascular risk factors using the Framingham 2009 risk score for renal transplant recipients and at end of the one year.
Surrogate markers for potential biological differences between the groups. [1 year]
Cardiovascular (CV) Biomarkers compared between each group. CV Biomarkers of interest in this study include: Chemokines (including ccl 1, 2, 15 and Clx 9 and 10) Thrombopoitin Cytokines IL 1, 2, 4, 6, 10, TGF, INF. These mediators are known to play a pivital role in atherosclerosis and progressive kidney failure.
Safety Measures [1 year]
Safety will be measured by estimated Glomerular filtration rate (GFR).
Change in 7-year MACE score for renal transplant recipients. [1 year]
Cardiovascular risk factors using the 7-year MACE calculator for renal transplant recipients and at end of the one year.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Age 18-74 years old.
At least six months after transplantation.
Lack of transplant rejection within the last 12 weeks.
Serum creatinine less than 300 umol/L at enrolment.
Negative urine pregnancy test for female patients of childbearing potential.
Consent to the study.
Not included in another interventional clinical trial within the last 90 days.

Exclusion Criteria:

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