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

NCT02058875 | Withdrawn Phase 4

• 1 other identifier: CERL080ACA15T
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Cardiovascular Disease; Cardiovascular Outcomes; Kidney Transplant Recipients; Kidney Transplantation

Outcome Measures

Primary Outcomes (4)

• Change in Framingham score for renal transplant recipients.

  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.

  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

  Safety will be measured by estimated Glomerular filtration rate (GFR).

  1 year

• Change in 7-year MACE score for renal transplant recipients.

  Cardiovascular risk factors using the 7-year MACE calculator for renal transplant recipients and at end of the one year.

  1 year

Study Arms (3)

Treatment Group

EXPERIMENTAL

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®; Drug: Neoral®

Control Group

ACTIVE COMPARATOR

25 patients continued on an mycophenolicacid (MPA) derivative, cyclosporine and prednisone.

Drug: Myfortic®; Drug: Cellcept®; Drug: Prednisone

Observation Group

NO INTERVENTION

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.

Interventions

Myfortic® DRUG

Also known as: mycophenolate sodium, MPA derivative

Control Group; Treatment Group

Neoral® DRUG

Also known as: cyclosporine

Treatment Group

Cellcept® DRUG

Control Group

Prednisone DRUG

Control Group

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Saskatchewan: lead

Study Sites (2)

Kidney Health Center

Regina, Saskatchewan, S4R 3C2, Canada

Location

St. Paul's Hospital

Saskatoon, Saskatchewan, S7M 0Z9, Canada

Location

Related Publications (44)

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MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Mycophenolic Acid; Cyclosporine; Prednisone

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Ahmed Shoker, MD

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: February 10, 2014
• Study Start: February 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 9, 2017

Record last verified: 2017-01

Locations

CA (2)