Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Calcineurin Inhibitor (CNI)-Free Regimen and a CNI-low Dose Regimen
- Conditions
- Kidney Transplantation
- Interventions
- Registration Number
- NCT00514514
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study is to compare renal function of immunosuppressive regimens with different relevance of the calcineurin inhibitor (CNI) cyclosporine: standard dose CNI, low dose CNI, CNI free in de novo kidney transplant patients after 12 months of therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 802
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CNI standard regimen Sandimmun Optoral Myfortic, Sandimmun Optoral and corticosteroids CNI standard regimen Simulect® Myfortic, Sandimmun Optoral and corticosteroids CNI free regimen Sandimmun Optoral CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids CNI low regimen Everolimus CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids CNI low regimen Sandimmun Optoral CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids CNI standard regimen Myfortic Myfortic, Sandimmun Optoral and corticosteroids CNI free regimen Everolimus CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids CNI free regimen Myfortic CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids
- Primary Outcome Measures
Name Time Method GFR Via Nankivell Method at Month 12 - CNI-Free vs Standard Regimen From randomization at BL2 (Month 3) to Month 12 post-transplant Demonstrate superiority of CNI-Free vs Standard Regimen in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. P-values are not adjusted
- Secondary Outcome Measures
Name Time Method GFR Via Nankivell Formula at Month 12 - All Regimens From randomization at BL2 (Month 3) to Month 12 post-transplant Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.
GFR at Month 12 Utilizing Cockcroft-Gault Formula From randomization at BL2 (Month 3) to Month 12 post-transplant Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
GFR at Month 12 Utilizing Modification of Diet in Renal Disease (MDRD) Method From randomization at BL2 (Month 3) to Month 12 post-transplant Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat:
For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.Efficacy Event Data From Baseline 2 (Month 3) to Month 6 From Baseline 2 (Month 3) to Month 6 Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).
Mean Change in Serum Creatinine From Month 3 to Month 12 From randomization at BL2 (Month 3) to Month 12 post-transplant Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Efficacy Event Data Baseline 2 (Month 3) to Month 12 From Baseline 2 (Month 3) to Month 12 Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).
Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk) From Baseline 2 (Month 3) to Month 12 The Framingham Score (based on LDL cholesterol level) estimates the coronary heart disease risk (%) of developing one of the following coronary heart diseases: angina pectoris, myocardial infarction, or coronary disease death, over the course of 10 years.
GFR Calculated Via Nankivell Formula at Month 60 From randomization at BL2 (Month 3) to Month 60 Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.
GFR at Month 60 Utilizing Cockcroft-Gault Formula From randomization at BL2 (Month 3) to Month 60 post-transplant Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl) For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
GFR at Month 60 Utilizing Modification of Diet in Renal Disease (MDRD) Method From randomization at BL2 (Month 3) to Month 60 post-transplant Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat:
For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.Mean Change in Serum Creatinine From Month 3 to Month 60 From randomization at BL2 (Month 3) to Month 60 post-transplant Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Efficacy Event Data After Month 12 to Month 60 Events starting after Month 12 Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇭Bern, Switzerland