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A 6-month, Prospective, Open-label, Randomized, Controlled, Pilot Study Evaluating the Efficacy, Safety and Toxicity of an Optimized Immunosuppressive Regimen of CellCept (Mycophenolate Mofetil, MMF) and Reduced Doses of Both Calcineurin-inhibitors and Prednisone in Renal Transplant Recipients With an Increased 10-year Coronary Heart Disease Risk


Phase 3
30 Years
N/A
Not Enrolling
Both
Kidney Transplantation, Cardiovascular Diseases

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Trial Information

A 6-month, Prospective, Open-label, Randomized, Controlled, Pilot Study Evaluating the Efficacy, Safety and Toxicity of an Optimized Immunosuppressive Regimen of CellCept (Mycophenolate Mofetil, MMF) and Reduced Doses of Both Calcineurin-inhibitors and Prednisone in Renal Transplant Recipients With an Increased 10-year Coronary Heart Disease Risk


Kidney transplant recipients are required to take medications called immunosuppressants to
lower their immune systems to help protect the donated kidney. The medications have
improved over the years and as a result the donated kidneys are generally working longer.
This allows the Transplant Team to focus more on the long term complications of kidney
transplantation such as cardiovascular disease.

There have been few prospective (looking forward) research studies looking at kidney
transplant recipient cardiovascular risk factors after transplant.

We know that immunosuppressive medications have a number of serious side effects that can
increase cardiovascular disease risk factors such as high blood pressure, high lipids (fats
in the blood), and high blood sugar. Medications such as tacrolimus, cyclosporine and
prednisone work well to protect the donated kidney but are also known to increase the risk
of developing or worsening cardiovascular disease.

CellCept is another type of immunosuppressive agent. CellCept is not associated as much
with the risk of developing cardiovascular disease.

This is a pilot study being done to collect information about cardiovascular risk factors in
kidney transplant recipients and to see if adjusting the immunosuppressive medications can
help to lower the overall risk for developing heart disease in the future.

This research study plans to enroll 45 participants from 2 different transplant centres in
Canada: St. Michael's Hospital in Toronto and St. Paul's Hospital in Saskatoon. The study
duration is approximately 7 months per participant. The study will be looking for
participants who are 30 years of age or older and who are at least 6 months after the
transplant operation.


Inclusion Criteria:



1. Renal transplant recipients who are ≥ 6 months post-day of transplant surgery.

2. Single organ kidney recipient (may be for first or repeat transplant).

3. Age ≥ 30 years of age as of the Day 0 visit.

4. 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.

5. 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.

6. Framingham risk factor score that exceeds the low comparative 10-year CHD risk, based
on age and gender.

7. 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.

8. Willingness and ability to complete protocol requirements.

9. Written informed consent.

Exclusion Criteria:

1. Contraindication to receiving MMF (CellCept) or increasing CellCept dose.

2. Clinically suspected acute rejection (AR) or BPAR within 3 months prior to the
baseline visit.

3. Proteinuria ≥ 1 g/24 hours

4. 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.

5. MDRD (4-variable) eGFR < 15 mL/min/1.73 m2

6. 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.

7. 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.

8. Pregnancy, lactation or (for women of childbearing potential) inability or decision
not to use a reliable method of contraception for the entire study duration.

9. Active infection requiring treatment.

10. Treatment with unlicensed investigational drugs, devices or other prohibited
medications - see Section 4.4.1

11. Participation in any other interventional clinical trial during the previous 4 weeks
or during this trial.

12. History of malignancy, other than non-melanoma skin cancer that has been totally
excised and has not recurred for >2 years.

13. History of psychological illness or condition that could interfere with the patient's
ability to understand or comply with the study requirements.

14. 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

- Influence the study result

- Affect the patient's ability to participate in the study

- Require a change in immunosuppression medication used or a dose change within
the next 6 months (unstable renal function, gout that may require treatment with
prednisone, etc)

- Reduce life expectancy. Examples include but are not limited to history of
noncompliance and transportation issues that could affect a participant's
ability to successfully complete the study requirements. Inability or refusal
to provide blood samples, end-stage disease of organs such as lung, liver or
heart.

15. Exclusion of patients who are hypersensitive to CellCept (mycophenolate mofetil),
mycophenolic acid or any component of the drug).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

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

Outcome Time Frame:

Baseline to Month 6

Safety Issue:

No

Principal Investigator

Dr. Ramesh Prasad, MBBS MSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Michael's Hospital, Toronto

Authority:

Canada: Health Canada

Study ID:

ML25073

NCT ID:

NCT01213394

Start Date:

October 2010

Completion Date:

December 2011

Related Keywords:

  • Kidney Transplantation
  • Cardiovascular Diseases
  • Framingham score
  • kidney transplant
  • immunosuppression
  • cardiovascular disease
  • CellCept
  • mycophenolate mofetil
  • Cardiovascular Diseases
  • Coronary Disease

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