Kidney Transplantation Clinical Trial
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
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
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 (i.e., < 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 ng/mL) 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 µmol/L, 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 µmol/L, proteinuria >1 g/day, 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 <2.5x103/µL, hemoglobin <80 g/dL, platelet count <100x103/µL,
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 measurement),and 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 g/day. 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.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04910867 -
APOL1 Genetic Testing Program for Living Donors
|
N/A | |
Completed |
NCT02723591 -
To Compare the Effects of Immediate-release Tacrolimus and Astagraf XL on Donor-Specific Antibody (DSA) Formation and the Development of Immune Activation (IA) in de Novo Kidney Transplant Recipients
|
Phase 4 | |
Completed |
NCT05945511 -
Silent Gallbladder Stone in Kidney Transplantation Recipients: Should it be Treated?
|
||
Completed |
NCT02234349 -
Bile Acids and Incretins in Pancreas Kidney Transplant Patients
|
N/A | |
Completed |
NCT04496401 -
PK Study in Diabetic Transplant récipients : From Twice-daily Tacrolimus to Once-daily Extended-release Tacrolimus
|
Phase 4 | |
Recruiting |
NCT05917795 -
Endoscopic Sleeve Gastroplasty With Endomina® for the Treatment of Obesity in Kidney Transplant Candidates
|
N/A | |
Not yet recruiting |
NCT05934383 -
Safety and Efficacy of Ultrasound Renal Denervation in Kidney Transplantation Patients With Uncontrolled Hypertension
|
N/A | |
Withdrawn |
NCT04936971 -
Introduction of mTor Inhibitors and the Activation of the Cytomegalovirus (CMV) -Specific Cellular Immune Response
|
Phase 4 | |
Not yet recruiting |
NCT04540640 -
Oxygenated Machine Preservation in Kidney Transplantation
|
N/A | |
Not yet recruiting |
NCT03090828 -
Economic Evaluation of an Education Platform for Patients With End-stage Renal Disease
|
N/A | |
Recruiting |
NCT02908139 -
Noninvasive Perioperative Monitoring of Arterial Stiffness, Volume and Nutritional Status in Stable Renal Transplant Recipients
|
N/A | |
Completed |
NCT02560558 -
Bela 8 Week Dosing
|
Phase 4 | |
Terminated |
NCT02417870 -
Ultra-low Dose Subcutaneous IL-2 in Renal Transplantation
|
Phase 1/Phase 2 | |
Recruiting |
NCT02154815 -
Pre-emptive Kidney Transplantation Quality of Life
|
N/A | |
Completed |
NCT02235571 -
iChoose Decision Kidney Aid for End-Stage Renal Disease Patients
|
N/A | |
Enrolling by invitation |
NCT01905514 -
ImPRoving Adherence to Immunosuppressive Therapy by Mobile Internet Application in Solid Organ Transplant Patients
|
N/A | |
Completed |
NCT02147210 -
Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1
|
N/A | |
Recruiting |
NCT01699360 -
The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients
|
Phase 4 | |
Completed |
NCT01672957 -
ORANGE Study: An Observational Study on Renal Function in Kidney Transplant Patients on Immunosuppressive Therapy Containing CellCept (Mycophenolate Mofetil)
|
N/A | |
Terminated |
NCT01436305 -
Optimization of NULOJIX® Usage As A Means of Avoiding CNI and Steroids in Renal Transplantation
|
Phase 2 |