Ignite Creation Date:
2024-05-05 @ 12:01 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00213590
Status:
COMPLETED
Last Update Posted:
2012-02-16
First Post:
2005-09-13
Brief Title:
Renal Function Evaluation After Reduction of Cyclosporine A Dose in Renal Transplant Patients
Sponsor:
University Hospital Rouen
Organization:
University Hospital Rouen
Study Overview
Official Title:
A Multicentric Randomized Opened Study to Evaluate Efficacy on Renal Function of an Immunosuppressant Regimen Based on Cyclosporine A Dose Reduction in Combination With Mycophenolate Mofetil From the Second Year of Renal Transplantation
Status:
COMPLETED
Status Verified Date:
2012-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DICAM
Brief Summary:
The purpose of the study is to show the efficacy of reduction of cyclosporine A exposure measured by the area under the curve by Bayesian estimator on the primary prevention of degradation of the renal function in renal transplant recipients
Detailed Description:
Study population Eligible patients were 18 to 75 years of age and primary or secondary renal transplant recipients in their second year posttransplant with stable serum creatinine levels ie 20 variation for the previous 3 months All patients must have received induction therapy been corticosteroid-free for at least 3 months and receiving combination maintenance therapy consisting of cyclosporine trough level 125 to 175 ngmL and mycophenolate mofetil CellCept F Hoffmann- La Roche AG Basel Switzerland 2 g daily
Patients at either low or high risk of graft dysfunction were ineligible a majority of the participating centers maintained low immunological risk patients on cyclosporine alone and those with a high risk of graft dysfunction were usually maintained on corticosteroids For this study low risk was defined as the presence of the following zero or one acute rejection episode with a return of renal function to previous levels after corticosteroid treatment panel-reactive antibody titer 25 serum creatinine level 125 µmolL age 25 years and donor age 40 years High risk was defined as the presence of at least one of the following a serum creatinine level 250 µmolL proteinuria 1 gday panel-reactive antibody titer 80 1 episode of T-cell-mediated rejection or at least one episode of antibody-mediated rejection posttransplant or the presence of vasculitis or systemic lupus erythematosus which usually were treated with corticosteroids
Other exclusion criteria were evidence of systemic infection or malignancy within the previous 5 years except adequately treated nonmetastatic basal or squamous cell carcinoma of the skin leukocyte count 25x103µL hemoglobin 80 gdL platelet count 100x103µL severe intestinal disorders pregnancy breast feeding current immunosuppressive treatment with drugs other than cyclosporine and mycophenolate mofetil Women of childbearing age were required to use adequate contraception during treatment with mycophenolate mofetil and for six weeks after its discontinuation
Study Endpoints The primary endpoint was the proportion of patients with treatment failure failure to prevent kidney dysfunction at 24 months which was a composite of graft loss histologically confirmed acute rejection or cyclosporine toxicity or a 15 increase in the mean serum creatinine level from the baseline assessment The mean of the current and two previous serum creatinine levels was used to determine the level at baseline the level at the nadir the time of the lowest serum creatinine measurementand the level at 2 years
The secondary endpoints included the change in estimated glomerular filtration rate eGFR from baseline calculated using the four-variable equation from the Modification of Diet in Renal Disease MDRD Study blood pressure urinary protein and lipid levels severe adverse events such as infection requiring hospitalization neoplasia or lymphoma and graft and patient survival
Study Follow-up and Procedures Weight blood pressure after a 10-minute rest serum creatinine and glucose levels a complete blood cell count and urinary protein levels were measured and the use of immunosuppressive antihypertensive and lipid-lowering drugs was recorded at baseline and every 2 months Serum lipid levels were measured at baseline and every 6 months Gynecologic and dermatologic examinations were performed at baseline and yearly Adverse events were recorded
Renal biopsies were performed when creatinine levels increased 20 relative to the nadir or when proteinuria was 1 gday The nadir level was used as a reference point to obviate the risk of missing the diagnosis of rejection in the low-exposure arm serum creatinine levels usually fell after the initiation of a low exposure regimen Biopsies were classified using Banff 1997 criteria by four senior pathologists blinded to the clinical information CNI-associated nephrotoxicity was graded mild moderate or severe according to the Banff 1997 chronicity rejection scores
Patients at either low or high risk of graft dysfunction were ineligible a majority of the participating centers maintained low immunological risk patients on cyclosporine alone and those with a high risk of graft dysfunction were usually maintained on corticosteroids For this study low risk was defined as the presence of the following zero or one acute rejection episode with a return of renal function to previous levels after corticosteroid treatment panel-reactive antibody titer 25 serum creatinine level 125 µmolL age 25 years and donor age 40 years High risk was defined as the presence of at least one of the following a serum creatinine level 250 µmolL proteinuria 1 gday panel-reactive antibody titer 80 1 episode of T-cell-mediated rejection or at least one episode of antibody-mediated rejection posttransplant or the presence of vasculitis or systemic lupus erythematosus which usually were treated with corticosteroids
Other exclusion criteria were evidence of systemic infection or malignancy within the previous 5 years except adequately treated nonmetastatic basal or squamous cell carcinoma of the skin leukocyte count 25x103µL hemoglobin 80 gdL platelet count 100x103µL severe intestinal disorders pregnancy breast feeding current immunosuppressive treatment with drugs other than cyclosporine and mycophenolate mofetil Women of childbearing age were required to use adequate contraception during treatment with mycophenolate mofetil and for six weeks after its discontinuation
Study Endpoints The primary endpoint was the proportion of patients with treatment failure failure to prevent kidney dysfunction at 24 months which was a composite of graft loss histologically confirmed acute rejection or cyclosporine toxicity or a 15 increase in the mean serum creatinine level from the baseline assessment The mean of the current and two previous serum creatinine levels was used to determine the level at baseline the level at the nadir the time of the lowest serum creatinine measurementand the level at 2 years
The secondary endpoints included the change in estimated glomerular filtration rate eGFR from baseline calculated using the four-variable equation from the Modification of Diet in Renal Disease MDRD Study blood pressure urinary protein and lipid levels severe adverse events such as infection requiring hospitalization neoplasia or lymphoma and graft and patient survival
Study Follow-up and Procedures Weight blood pressure after a 10-minute rest serum creatinine and glucose levels a complete blood cell count and urinary protein levels were measured and the use of immunosuppressive antihypertensive and lipid-lowering drugs was recorded at baseline and every 2 months Serum lipid levels were measured at baseline and every 6 months Gynecologic and dermatologic examinations were performed at baseline and yearly Adverse events were recorded
Renal biopsies were performed when creatinine levels increased 20 relative to the nadir or when proteinuria was 1 gday The nadir level was used as a reference point to obviate the risk of missing the diagnosis of rejection in the low-exposure arm serum creatinine levels usually fell after the initiation of a low exposure regimen Biopsies were classified using Banff 1997 criteria by four senior pathologists blinded to the clinical information CNI-associated nephrotoxicity was graded mild moderate or severe according to the Banff 1997 chronicity rejection scores
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None