Mycophenolate Mofetil for Reducing Cardiovascular Risk in Renal Transplant Recipients

NCT01213394 | Terminated Phase 3

• 1 other identifier: ML25073
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine if adding or increasing the dose of CellCept while lowering the dose of tacrolimus (Prograf or Advagraf) or cyclosporine (Neoral), and/or steroids can reduce the likelihood of developing coronary heart disease in the next 10 years. The investigators will calculate the change in risk of developing coronary heart disease using the Framingham score. The Framingham score is a mathematical equation that includes the following information: Age, Gender, Diabetes status, Smoking status, Lipids, Blood Pressure. The Framingham score estimates how likely it is that someone will develop coronary heart disease over the next 10 years.

Conditions

Kidney Transplantation; Cardiovascular Diseases

Keywords

Framingham score; kidney transplant; immunosuppression; cardiovascular disease; CellCept; mycophenolate mofetil

Outcome Measures

Primary Outcomes (2)

• The change in the Framingham 10-yr age and gender adjusted score for coronary heart disease from baseline to Month 6

  Baseline to Month 6

• The incidence of a composite of acute rejection (clinically suspected and biopsy-proven), graft loss or patient death.

  Month 6

Secondary Outcomes (13)

• Framingham point total

  Baseline to Month 6

• Day and night blood pressure

  Baseline to Month 6

• Glucose metabolism

  Baseline to Month 6

• Lipid metabolism

  Baseline to Month 6

• Change in renal function

  Baseline to Month 6

Study Arms (2)

CellCept optimization

EXPERIMENTAL

Drug: mycophenolate mofetil

Control

ACTIVE COMPARATOR

Other: standard immunosuppression

Interventions

mycophenolate mofetil DRUG

Introduction of CellCept or increase in the dose of CellCept to a maximum of 2 g/day. In patients not already receiving CellCept, azathioprine (AZA), enteric-coated mycophenolate sodium (EC-MPS) or sirolimus (SRL) will be discontinued and replaced by CellCept in divided doses to a maximum of 2 g/day. CNI doses will be reduced to conform to the target trough levels in the low-dose CNI arms of the ELITE-Symphony study +/- steroid dose reduction. Any CNI dose change will require measurement of CNI trough levels at 7 days post dose change +/- 3 days. Target CNI trough levels in the Symphony study: * Low-dose CsA: Initial oral dose of 1-2 mg/kg bid, to achieve a target trough level of 50-100 ng/mL. * Low-dose TAC: Initial oral dose of 0.1 mg/kg/day divided into two doses\* with a target trough level of 3-7 ng/mL (\*Advagraf may also be used at a dose of 0.1 mg/kg once daily with a target trough level of 3-7 ng/mL)

Also known as: CellCept, MMF

CellCept optimization

standard immunosuppression OTHER

Current immunosuppressive therapy will be maintained throughout the study unless a change is required for safety reasons.

Control

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Renal transplant recipients who are ≥ 6 months post-day of transplant surgery.
• Single organ kidney recipient (may be for first or repeat transplant).
• Age ≥ 30 years of age as of the Day 0 visit.
• Immunosuppressive regimen consisting of a CNI (cyclosporine \[CsA, Neoral\] or tacrolimus \[TAC, Prograf or Advagraf\], corticosteroids and either MMF (CellCept), EC-MPS (Myfortic), AZA (Imuran) or SRL (Rapamune) at the baseline visit. Patients are to be maintained on the same dose(s) for at least 4 weeks prior to study enrolment.
• If the patient is taking an MPA immunosuppressant at the time of the screening visit, the MMF (CellCept) dose must be ≤ 1500 mg/day; or the EC-MPS (Myfortic) dose must be ≤ 1080 mg/day.
• Framingham risk factor score that exceeds the low comparative 10-year CHD risk, based on age and gender.
• Presence of at least one established CV risk factor at baseline warranting modification of the immunosuppressive regimen including:
• Hypertension: Blood pressure ≥ 140 mmHg systolic and/or ≥ 90 mmHg diastolic and/or requiring ≥ 1 antihypertensive medication.
• Diabetes mellitus: Established diabetes requiring treatment with oral hypoglycemic agents or insulin, or known IFG or IGT based on 75-g oral glucose tolerance testing (2003 Canadian Diabetes Association criteria).
• Hyperlipidemia: TC ≥ 5.2 mmol/L, or LDL-C ≥ 2.6 mmol/L, or TG ≥ 1.7 mmol/L, or TC:HDL ≥ 4 and/or requiring ≥ 1 anti-hyperlipidemia agent.
• Willingness and ability to complete protocol requirements.
• Written informed consent.

You may not qualify if:

• Contraindication to receiving MMF (CellCept) or increasing CellCept dose.
• Clinically suspected acute rejection (AR) or BPAR within 3 months prior to the baseline visit.
• Proteinuria ≥ 1 g/24 hours
• Treatment with AZA (Imuran), EC-MPS (Myfortic) or SRL (Rapamune) and patient or physician decision not to discontinue these agents and switch to MMF (CellCept) at the time of randomization.
• MDRD (4-variable) eGFR \< 15 mL/min/1.73 m2
• Patients who currently exceed thresholds for plasma glucose, cholesterol or blood pressure. Patients may be re-considered 1 month after the treatment is in place and no further therapeutic changes are anticipated.
• Patients who require changes to their blood pressure, blood sugar or blood lipid management between the Screening Visit and Day 0. Patients may be re-considered 1 month after the adjusted treatment is in place and no further therapeutic changes are anticipated.
• Pregnancy, lactation or (for women of childbearing potential) inability or decision not to use a reliable method of contraception for the entire study duration.
• Active infection requiring treatment.
• Treatment with unlicensed investigational drugs, devices or other prohibited medications - see Section 4.4.1
• Participation in any other interventional clinical trial during the previous 4 weeks or during this trial.
• History of malignancy, other than non-melanoma skin cancer that has been totally excised and has not recurred for \>2 years.
• History of psychological illness or condition that could interfere with the patient's ability to understand or comply with the study requirements.
• Presence of other significant diseases or issues which, in the opinion of the sponsor-investigator, may:
• Put the patient at risk as a result of study participation

Sponsors & Collaborators

• Ramesh Prasad: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5C 2T2, Canada

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Dr. Ramesh Prasad, MBBS MSc

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff Nephrologist

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: October 4, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: April 19, 2012

Record last verified: 2012-04

Locations

CA (1)