Study Comparing Effect On Carotid Atherosclerosis Following Conversion From Tacrolimus To Sirolimus Post-Transplant In Kidney Transplant Patients

Phase 3

Terminated

Conditions: Atherosclerosis
Kidney Failure

Interventions: Drug: tacrolimus
Drug: sirolimus
Drug: mycophenolate mofetil
Drug: prednisone

Registration Number: NCT00311311

Lead Sponsor: Pfizer

Brief Summary: The purpose of this study is to determine whether immunosuppression by tacrolimus, mycophenolate mofetil, and prednisone compared to conversion to sirolimus, mycophenolate mofetil, and prednisone affect the progression of atherosclerosis in renal transplant recipients.

Detailed Description: A decision to terminate the study was taken in November 2011 and a communication to that effect sent to all participating sites on November 18. All sites were asked to have patients returned to the sites and have all end of study procedures performed by Dec 31, 2011.

The decision to terminate this study was made following the conduct of an interim analysis which demonstrated that the study did not reach its primary endpoint. The termination of this study was not driven by any safety concerns and had no impact on subject safety and well-being.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 72

Inclusion Criteria

At least one of the following characteristics:

History of dialysis for at least 3 years.
History of diabetes for at least 5 years.
Hypertension or ischemic nephropathy as a cause of the end stage renal disease or loss of the first transplant.
History of coronary artery disease, stroke, myocardial infarction, or amputation for vascular disease.

Exclusion Criteria

History of malignancy within the last 5 years (except adequately treated skin cancer).
Recipients of non-renal organ transplant.
Active gastrointestinal disease that may interfere with drug absorption.
Active HIV, hepatitis B or C infection.
Women who are pregnant or breastfeeding.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	tacrolimus	Tacrolimus + MMF + Steroids
1	mycophenolate mofetil	Tacrolimus + MMF + Steroids
1	prednisone	Tacrolimus + MMF + Steroids
2	sirolimus	Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant
2	tacrolimus	Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant
2	mycophenolate mofetil	Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant
2	prednisone	Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant

Primary Outcome Measures

Name	Time	Method
Annual Change Rate in Total Plaque Volume (TPV) From Pre-conversion Baseline to 12 Months Post-transplant	Pre-conversion baseline and 12 months post-transplant	Within-subject annual change rate in TPV in the left and right distal common carotid arteries from the pre-conversion baseline to 12 months post kidney transplant as determined by ultrasound. Annual change rate equals (=) (TPV at month 12 post-transplant minus \[-\] TPV at pre-conversion baseline) divided (/) by imaging interval in years. TPV is the sum of assessment in left and right distal common carotid arteries.
TPV at Pre-conversion Baseline	Pre-conversion baseline	TPV is the sum of the assessment in left and right distal common carotid arteries.

Secondary Outcome Measures

Name	Time	Method
CIMT at Pre-conversion Baseline	Pre-conversion baseline	Mean CIMT=average of left CIMT and right CIMT.
Number of Participants Who Used Anti-hypertensive Medications	From consent to conversion, from conversion to Month 12, from Months 12 to 24, and from Months 24 to 36 post-transplant	Participants who reported "yes" for taking anti-hypertensive medications as concomitant medication.
Annual Change Rate in Carotid Intima Media Thickness (CIMT) From Pre-conversion Baseline at 12, 18, 24 and 36 Months Post-transplant	Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant	Within-subject annual change rate in CIMT as determined by ultrasound. Mean CIMT=average of left CIMT and right CIMT. Annual CIMT Change Rate (mm/year) = (CIMT at Month x Post-transplant Visit - CIMT at Conversion Baseline) / Imaging interval in years.
Change From Pre-conversion Baseline in Fasting Lipid Parameters at 12, 18, 24 and 36 Months Post-transplant	Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant	Total Cholesterol (TC), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL) and Triglyceride (Tg) blood concentrations. Higher levels of TC, LDL and Tg are less desirable. Lower levels of HDL are less desirable. Change for each parameter = value at 12, 18, 24 and 36 months post-transplant - value at pre-conversion baseline.
Change From Pre-conversion Baseline in Insulin at Months 12, 24, and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Fasting insulin. Change = value at month x post-transplant - pre-conversion baseline.
Change From Pre-conversion Baseline in Glycosylated Hemoglobin(HbA1C) at Months 12, 24, and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	HbA1C, change = value at month x post-transplant - pre-conversion baseline.
Change From Pre-conversion Baseline in Adiponectin at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Adiponectin is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates less risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Vitamin B12 at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Vitamin B12 is a biomarker for cardiovascular disease and atherosclerosis risk. A lower level indicates a greater risk. Change = month x post-transplant values - pre-conversion values.
Change From Pre-conversion Baseline in Folate at 12, 24 and 36 Months Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Folate is a biomarker for cardiovascular disease and atherosclerosis risk. A lower level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Glucose at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Fasting plasma glucose. Change = value at month x post-transplant - pre-conversion baseline values.
Change From Pre-conversion Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Months 12, 24 and 36 Post-transplant.	Pre-conversion baseline, 12, 24 and 36 months post-transplant	hsCRP is a biomarker of cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Tumor Necrosis Factor Alpha (TNF-alpha) at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	TNF-alpha is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Endothelin-1 at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Endothelin-1 is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Lipoprotein(a) at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Lipoprotein(a) is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Number of Participants Who Used Lipid Lowering Therapies	From consent to conversion, from conversion to Month 12, from Months 12 to 24, and from Months 24 to 36 post-transplant	Participants who reported "yes" for taking lipid lowering therapies as concomitant medication.
Annual Rate of Change in TPV From Pre-conversion Baseline to 18, 24 and 36 Months Post Transplant	Pre-conversion baseline, and 18, 24 and 36 months post-transplant	Within-subject annual change rate in TPV in the left and right distal common carotid arteries from the pre-conversion baseline to 18, 24 and 36 months post kidney transplant as determined by ultrasound. Annual change rate equals (=) (TPV at month 18, 24 and 36 post-transplant minus \[-\] TPV at pre-conversion baseline) divided (/) by imaging interval in years. TPV is the sum of assessment in left and right distal common carotid arteries.
Change From Pre-conversion Baseline in Carotid Plaque Roughness at 12 and 24 Months Post-transplant	Pre-conversion baseline, 12, and 24 months post-transplant	Carotid plaque roughness as determined by ultrasound. Change equals (=) value at post-transplant month x minus (-) pre-conversion baseline.
Change From Pre-conversion Baseline in Interleukin-6 (IL-6) at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	IL-6 is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion values.
Change From Pre-conversion Baseline in Uric Acid at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Uric Acid is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Homocysteine at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Homocysteine is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Change From Pre-conversion Baseline in Fibrinogen at Months 12, 24 and 36 Post-transplant	Pre-conversion baseline, 12, 24 and 36 months post-transplant	Fibrinogen is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.