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

アクティブコンパレータ：1

Tacrolimus + MMF + Steroids

薬：tacrolimus

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. The target trough level of TAC will be maintained at 3-10 ng/mL through to the end of the study.

他の名前：

• CNI

薬：mycophenolate mofetil

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol MMF or MPS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum oral dose of MMF ≥ 500 mg/day or MPS ≥ 360 mg/day by the Pre-Conversion visit at month 3-4 post-transplantation. At the discretion of the investigator, MMF may be changed to MPS, or MPS may be changed to MMF. MMF is to be continued at ≥ 500 mg/day dose or MPS is to be continued at ≥ 360 mg/day dose through to the end of study.

他の名前：

• MMF, MPS

薬：prednisone

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol CCS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum of 5 mg/day of prednisone orally or the alternate day equivalent by the Pre-Conversion visit at month 3-4 post-transplant. Continue administration of prednisone as per local standard of care to a minimum dose of 2.5 mg/day or alternate day equivalent dose to the end of the study. Withdrawal of CCS is prohibited.

他の名前：

• CCS

薬：tacrolimus

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. Reintroduction of TAC or introduction of CsA is not permitted in the SRL Therapy group.

他の名前：

• CNI

実験的：2

Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant

薬：tacrolimus

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. The target trough level of TAC will be maintained at 3-10 ng/mL through to the end of the study.

他の名前：

• CNI

薬：mycophenolate mofetil

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol MMF or MPS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum oral dose of MMF ≥ 500 mg/day or MPS ≥ 360 mg/day by the Pre-Conversion visit at month 3-4 post-transplantation. At the discretion of the investigator, MMF may be changed to MPS, or MPS may be changed to MMF. MMF is to be continued at ≥ 500 mg/day dose or MPS is to be continued at ≥ 360 mg/day dose through to the end of study.

他の名前：

• MMF, MPS

薬：prednisone

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol CCS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum of 5 mg/day of prednisone orally or the alternate day equivalent by the Pre-Conversion visit at month 3-4 post-transplant. Continue administration of prednisone as per local standard of care to a minimum dose of 2.5 mg/day or alternate day equivalent dose to the end of the study. Withdrawal of CCS is prohibited.

他の名前：

• CCS

薬：tacrolimus

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. Reintroduction of TAC or introduction of CsA is not permitted in the SRL Therapy group.

他の名前：

• CNI

薬：sirolimus

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol.

On study Day 1 Conversion, the daily dose of TAC will not be taken, and SRL is initiated as a single 5-10 mg loading dose, followed by 3 mg/day on subsequent days, adjusted to maintain a SRL target trough level of 8-15 ng/mL through to month 24 post-transplant, then 5-12 ng/mL to the end of month 36 post-transplant.

Annual Change Rate in Total Plaque Volume (TPV) From Pre-conversion Baseline to 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

TPV is the sum of the assessment in left and right distal common carotid arteries.

Annual Change Rate in Carotid Intima Media Thickness (CIMT) From Pre-conversion Baseline at 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.

CIMT at Pre-conversion Baseline

Mean CIMT=average of left CIMT and right CIMT.

Change From Pre-conversion Baseline in Carotid Plaque Roughness at 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 Fasting Lipid Parameters at 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 Glucose at Months 12, 24 and 36 Post-transplant

Fasting plasma glucose. Change = value at month x post-transplant - pre-conversion baseline values.

Change From Pre-conversion Baseline in Insulin at Months 12, 24, and 36 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

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

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 High Sensitivity C-Reactive Protein (hsCRP) at Months 12, 24 and 36 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

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

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 Interleukin-6 (IL-6) at Months 12, 24 and 36 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 Homocysteine at Months 12, 24 and 36 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 Lipoprotein(a) at Months 12, 24 and 36 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.

Change From Pre-conversion Baseline in Fibrinogen at Months 12, 24 and 36 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.

Change From Pre-conversion Baseline in Vitamin B12 at Months 12, 24 and 36 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 Uric Acid at Months 12, 24 and 36 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 Folate at 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.

Number of Participants Who Used Lipid Lowering Therapies

Participants who reported "yes" for taking lipid lowering therapies as concomitant medication.

Number of Participants Who Used Anti-hypertensive Medications

Participants who reported "yes" for taking anti-hypertensive medications as concomitant medication.

Annual Rate of Change in TPV From Pre-conversion Baseline to 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.