The aim of this study is to assess the safety and efficacy of corticosteroid discontinuation versus cyclosporine micro emulsion discontinuation in recipients receiving reduced exposure cyclosporine micro emulsion and corticosteroids plus enteric-coated mycophenolate sodium (EC-MPS) initially, changed to everolimus at 2 weeks post-transplant. These two groups will be compared to a third control group, who will receive treatment consisting of cyclosporine micro emulsion, enteric-coated mycophenolate sodium (EC-MPS) and steroids.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
126
Royal Prince Alfred Hospital
NSW, Australia
Westmead Hospital
NSW, Australia
Princess Alexandra Hospital
QLD, Australia
Monash Medical Centre
Sale, Australia
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (12 Months Analysis)
The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.
Time frame: At Month 12
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (36 Months Analysis)
The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.
Time frame: At Month 24 and 36
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (12 Months Analysis)
A biopsy-proven acute rejection is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.
Time frame: At Month 12
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis)
A biopsy-proven acute rejection is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.
Time frame: At Month 12, 24 and 36
Number of Participants With Composite Endpoint of Treatment Failure (12 Months Analysis)
Composite endpoint of treatment failure includes biopsy-proven acute rejection (BPAR), graft loss, death and loss-to-follow-up. A BPAR is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification. The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
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Queen Elizabeth Hospital
Sale, Australia
Royal Melbourne Hospital
VIC, Australia
Sir Charles Gairdner Hospital
WA, Australia
Time frame: Month 12
Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis)
Composite endpoint of treatment failure includes biopsy-proven acute rejection (BPAR), graft loss, death and loss-to-follow-up. A BPAR is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification. The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Time frame: At Month 12, 24 and 36
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (12 Months Analysis)
A per-protocol biopsy was performed at Baseline and Month 12 and read by an independent blinded pathologist in order to assess chronic allograft nephropathy. Chronic rejection is characterized by a slow progressive decline in renal function and is typically preceded by the histological picture of chronic allograft nephropathy. The presence of biopsy confirmed Grade I, II or III chronic allograft nephropathy by Banff 97 criteria was assessed on all optional biopsies obtained for clinical suspicion of chronic rejection. Data summarized by 3 categories. "Yes" - Patients with histological evidence of CAN ; "No" - Patients with histological evidence of CAN and "Not Done" - Central protocol defined kidney allograft biopsies were not done.
Time frame: At Month 12
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (36 Months Analysis)
Chronic rejection is characterized by a slow progressive decline in renal function and is typically preceded by the histological picture of chronic allograft nephropathy. The presence of biopsy confirmed Grade I, II or III chronic allograft nephropathy by Banff 97 criteria was assessed on all optional biopsies obtained for clinical suspicion of chronic rejection. Data summarized by 3 categories. "Yes" - Patients with histological evidence of CAN ; "No" - Patients with histological evidence of CAN and "Not Done" - Central protocol defined kidney allograft biopsies were not done.
Time frame: At Month 36
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis)
Based on Banff 97 criteria, sub clinical acute rejection can be: GRADE IA - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IB - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IIA - Cases with significant interstitial infiltration and mild to moderate intimal arteritis (v1). GRADE IIB - Cases with moderate to severe intimal arteritis comprising \>25% of the luminal area (v2). GRADE III - Cases with "transmural" arteritis or fibrinoid change and necrosis of medial smooth muscle cells (v3). "Borderline" category is used when no intimal arteritis is present, but there are foci of mild tubulitis (1 to 4 mononuclear cells/tubular cross section).
Time frame: At Month 12
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis)
Based on Banff 97 criteria, sub clinical acute rejection can be: GRADE IA - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IB - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IIA - Cases with significant interstitial infiltration and mild to moderate intimal arteritis (v1). GRADE IIB - Cases with moderate to severe intimal arteritis comprising \>25% of the luminal area (v2). GRADE III - Cases with "transmural" arteritis or fibrinoid change and necrosis of medial smooth muscle cells (v3). "Borderline' category is used when no intimal arteritis is present, but there are foci of mild tubulitis (1 to 4 mononuclear cells/tubular cross section).
Time frame: At Month 36
Mean Serum Creatinine (12 Months Analysis)
Time frame: At Month 12
Mean Serum Creatinine (36 Months Analysis)
Time frame: At Month 12, 18, 24 and 36
Creatinine Clearance (CrCl) Calculated by the Cockcroft-Gault Formula (12 Months Analysis)
Creatinine clearance were calculated according to the Cockcroft-Gault formula: CrCl (males) = (140-A) × BW/(72 × Cr) CrCl (females) = CrCl (males) × 0.85 where A is age \[years\], BW is body weight \[kg\], and Cr is the serum concentration of creatinine \[mg/dL\]. The Cockcroft-Gault formula estimates creatinine clearance based on serum creatinine level, body weight, and age.
Time frame: At Month 12
Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis)
Creatinine clearance were calculated according to the Cockcroft-Gault formula: CrCl (males) = (140-A) × BW/(72 × Cr) CrCl (females) = CrCl (males) × 0.85 where A is age \[years\], BW is body weight \[kg\], and Cr is the serum concentration of creatinine \[mg/dL\]. The Cockcroft-Gault formula estimates creatinine clearance based on serum creatinine level, body weight, and age.
Time frame: At Month 12, 24 and 36
Mean Urine Albumin/Creatinine Ratio (ACR) as Measurement of Proteinuria (12 Months Analysis)
Proteinuria is measured by spot morning urine Albumin/Creatinine Ratio \[ACR\]. When the ACR is more than or equal to 30 mg/mmol then it is known as proteinuria.
Time frame: At Month 12
Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis)
Proteinuria is measured by spot morning urine Albumin/Creatinine Ratio \[ACR\]. When the ACR is more than or equal to 30 mg/mmol then it is known as proteinuria.
Time frame: At Month 12, 18, 24 and 36
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis)
The symptoms of post transplant diabetes mellitus (PTDM) and impaired fasting glucose are defined as any of the following conditions: 1. Patients receiving glucose lowering treatment 2. Fasting plasma glucose (FPG) \>= 126 mg/dL on 2 separate occasions 3. Hemoglobin subtype A1c (HbA1c) \> 6.5% 4. Diabetes reported as treatment emergent AE with end date \> Day 15
Time frame: At Month 12
Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis)
The symptoms of new onset diabetes mellitus after transplantation (NODAT) and impaired fasting glucose are defined as any of the following conditions: 1. Patients receiving glucose lowering treatment 2. 2 fasting plasma glucose (FPG) values \>= 126 mg/dL or 2 random plasma glucose (RPG) values \>= 200 mg/dL or FPG value \>= 126 mg/dL and 1 RPG value \>= 200 mg/dL 3. Diabetes reported as treatment emergent AE with end date \> Day 15
Time frame: At Month 36
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis)
Notable abnormal systolic blood pressure is defined as : * Either an increase of \>=30 that results in \>=180 or \>200 (mm/Hg) * OR a decrease of \>=30 that results in \<=90 or \<75 (mm/Hg)from baseline Notable abnormal diastolic blood pressure is defined as : * Either an increase of \>=20 that results in \>=105 or \>115 (mm/Hg) * OR a decrease of \>=20 that results in \<=50 or \<40 (mm/Hg) from baseline
Time frame: Baseline, Overall post-baseline up to 12 month
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis)
Notable abnormal systolic blood pressure is defined as : * Either an increase of \>=30 that results in \>=180 or \>200 (mm/Hg) * OR a decrease of \>=30 that results in \<=90 or \<75 (mm/Hg) from baseline Notable abnormal diastolic blood pressure is defined as : * Either an increase of \>=20 that results in \>=105 or \>115 (mm/Hg) * OR a decrease of \>=20 that results in \<=50 or \<40 (mm/Hg) from baseline
Time frame: Baseline, Overall post baseline up to Month 36
Number of Participants With Erythropoietin Usage (12 Months Analysis)
Time frame: Month 12
Number of Participants With Erythropoietin Usage (36 Months Analysis)
Time frame: Month 36
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis)
SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales. The 8 subscales are: Physical functioning (PF), Role-physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role-emotional (RE) and Mental health (MH). Score for eash sub-scale has been standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL.
Time frame: At Month 12
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis)
SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales. The 8 subscales are : Physical functioning (PF), Role-physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role-emotional (RE) and Mental health (MH). Score for each sub-scale has been standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL.
Time frame: At Month 24
Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (12 Months Analysis)
This analysis is reporting number of participants hospitalized for reasons (such as acute rejection, infection, gastrointestinal (GI) events, cardiovascular event, metabolic disorder and Other) other than primary transplantation.
Time frame: Month 12
Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (36 Months Analysis)
This analysis is reporting number of participants hospitalized for reasons (such as acute rejection, infection, gastrointestinal (GI) events, cardiovascular event, metabolic disorder and Other) other than primary transplantation.
Time frame: Month 36
Number of Participants With Employment Status (12 Months Analysis)
The various employment status reported are: * Employed/self employed full time * Employed part time * Unemployed * Homemaker * Volunteer * Permanently disabled * Non-permanently disable * Retired * Other
Time frame: At screening (at day 0 +/- 7 days ), At Month 12
Number of Participants With Employment Status (36 Months Analysis)
The various employment status reported are: * Employed/self employed full time * Employed part time * Unemployed * Homemaker * Volunteer * Permanently disabled * Non-permanently disable * Retired * Other
Time frame: At screening (at day 0 +/- 7 days ), At Month 36
Number of Participants With Wound Problems(12 Months Analysis)
Patients with any wound healing problem such as infection related to kidney surgery, dehiscence, lymphocele, hernia, seroma, hematoma, ureteral anastomotic complication and other were reported in this analysis.
Time frame: At Month 12
Number of Participants With Any Wound Problems (36 Months Analysis)
Patients with any wound healing problem such as infection related to kidney surgery, dehiscence, lymphocele, hernia, seroma, hematoma, ureteral anastomotic complication and other were reported in this analysis.
Time frame: At Month 12, 24 and 36
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis)
Notable abnormal total cholesterol is defined as : High: \>= 9.1 mmol/L , normal range is 0.00 - 5.17 mmol/L Notable abnormal triglycerides is defined as : High: \>= 8.5 mmol/L, normal range is 0.30 - 2.00 mmol/L
Time frame: Overall post baseline up to month 12
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis)
Notable abnormal total cholesterol is defined as : High: \>= 9.1 mmol/L , normal range is 0.00 - 5.17 mmol/L Notable abnormal triglycerides is defined as : High: \>= 8.5 mmol/L, normal range is 0.30 - 2.00 mmol/L
Time frame: Overall Post Baseline up to month 36
Number of Participants With Antibody-mediated Rejection Per Treatment Group (12 Months Analysis)
Time frame: At Month 12
Number of Participants With Antibody-mediated Rejection Per Treatment Group (36 Months Analysis)
Time frame: At Month 12, 24 and 36
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis)
The influence of demographic characteristics and comorbidities on incidence of BPAR were analyzed in the following way: Demographic characteristics were age (\<55 years, ≥55 years), Expanded criteria Donor (ECD) organ (donor age \>60 years or donor non heart-beating and donor age \>50), gender, living vs. deceased donor, Body Mass Index (BMI) classes (underweight \<18.5, normal 18.5 - \<25.0, overweight 25.0 - \<30.0, obesity 30.0 and above), years on dialysis before transplantation (\<1, 1-5, \>5 years). Comorbidities were diabetes, hypertension, cardiovascular diseases/events, nephrosclerosis, glomerulonephritis/glomerular disease, polycystic disease, and Cytomegalovirus status.
Time frame: At Month 12
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis)
The influence of demographic characteristics and comorbidities on incidence of BPAR were analyzed in the following way: Demographic characteristics were age (\<55 years, ≥55 years), Expanded Criteria Donor \[ECD\] organ (donor age \>60 years or donor non heart-beating and donor age \>50), gender, living vs. deceased donor, Body Mass Index (BMI) classes (underweight \<18.5, normal 18.5 - \<25.0, overweight 25.0 - \<30.0, obesity 30.0 and above), years on dialysis before transplantation (\<1, 1-5, \>5 years). Comorbidities were diabetes, hypertension, cardiovascular diseases/events, nephrosclerosis, glomerulonephritis/glomerular disease, polycystic disease, and Cytomegalovirus status.
Time frame: At Month 36
Number of Patient Survival and Graft Survival (12 Months Analysis)
Time frame: At Month 12
Number of Patient Survival and Graft Survival (36 Months Analysis)
Time frame: At Month 12, 24 and 36
Change in Bone Mineral Density Between Week 2 and Month 24 (36 Months Analysis)
Measurements of bone mineral density (BMD) by Dual Energy X-ray Absorptiometry (DEXA) were done at Week 2 and Month 24. Change in BMD between week 2 and Month 24 were done for neck of femur and lumbar spine.
Time frame: Week 2, Month 24