Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium
Ключови думи
Резюме
Описание
A. Primary Objectives:
1. The percentage of patients who develop chronic allograft injury (CAI) progression during the first 12 months post-transplant protocol biopsy (i.e., higher grade of IF/TA at either the 6 or 12 month protocol biopsy in comparison with the baseline biopsy).
2. The incidence rate of biopsy-proven acute rejection (BPAR) during the first 12 months post-transplant.
B. Secondary Objectives:
1. Adverse events including graft loss (death-censored and death-uncensored), and death at 12 months post-transplant.
2. Incidence rate and severity (severity of CAI at 12 months as well), based upon careful review of all clinically indicated and protocol biopsies.
3. Renal function as determined by serum creatinine and estimated glomerular filtration rate (eGFR) (calculated using the abbreviated MDRD formula) at 12, months post-transplant. Use of multivariable analysis to compare renal function as well as BPAR and CAI progression will also be performed (particularly, after adjusting for the significant effects of donor age, recipient age, race/ethnicity, and any other predictors).
5. Adverse events including withholding (for ≥ 28 days) or discontinuance of study medications (and reasons why), new onset diabetes mellitus after transplantation (NODAT), infections requiring hospitalization, and requirement of anti-lipid medication at 12 months post-transplant.
6. Avoidance of the requirement for maintenance corticosteroid therapy after renal transplantation.
7. Allowance of reduced maintenance tacrolimus dosing (rTd).
Дати
| Последна проверка: | 09/30/2016 |
| Първо изпратено: | 03/05/2012 |
| Очаквано записване подадено: | 09/03/2012 |
| Първо публикувано: | 09/06/2012 |
| Изпратена последна актуализация: | 10/20/2016 |
| Последна актуализация публикувана: | 12/14/2016 |
| Дата на първите подадени резултати: | 06/19/2016 |
| Дата на първите подадени резултати от QC: | 10/20/2016 |
| Дата на първите публикувани резултати: | 12/14/2016 |
| Действителна начална дата на проучването: | 10/31/2012 |
| Приблизителна дата на първично завършване: | 11/30/2014 |
| Очаквана дата на завършване на проучването: | 11/30/2014 |
Състояние или заболяване
Интервенция / лечение
Drug: Tacrolimus
Drug: Tacrolimus and Everolimus
Drug: Tacrolimus and Enteric-Coated Mycophenolate Sodium (EC-MPS)
Drug: Corticosteroids
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: Tacrolimus and Everolimus Patients in both arms will receive reduced tacrolimus dosing (rTd), 0.1 mg/kg PO divided in two daily doses - beginning when serum Cr decreases to a level of <4 mg/dl (i.e., acceptable renal transplant function) postoperatively. Target tacrolimus trough levels during the first year post-transplant and thereafter will be 5-8 ng/ml.
Everolimus initiated within 24 hours post-transplant (i.e., immediately following randomization) at 0.75mg PO BID and will be adjusted in order to achieve target everolimus trough levels of 3-8 ng/ml. | Drug: Tacrolimus and Everolimus Everolimus initiated at 0.75 PO BID and will be adjusted in order to achieve target everolimus trough levels of 3-8 ng/ml. |
| Active Comparator: Tacrolimus and Enteric-Coated Mycophenolate Sodium (EC-MPS) Patients in both arms will receive reduced tacrolimus dosing (rTd), 0.1 mg/kg PO divided in two daily doses - beginning when serum Cr decreases to a level of <4 mg/dl (i.e., acceptable renal transplant function) postoperatively. Target tacrolimus trough levels during the first year post-transplant and thereafter will be 5-8 ng/ml.
EC-MPS will be initiated at 720 mg PO BID starting on the first post-operative day. | Drug: Tacrolimus and Enteric-Coated Mycophenolate Sodium (EC-MPS) EC-MPS 720 mg PO BID - beginning on 1st postoperative day. |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: - Weight > 40 kg. - Deceased donor (SCD) or LD. - Donor-recipient 1 haplotype matched pairs with a minimum matching of 1 HLA DR antigen. - Negative standard cross match for T cells. - Pretransplant panel reactive antibodies of < 30%. - Graft required to be functional, producing at least 100ml of urine within 24hr after transplantation. Exclusion Criteria: - Previously received or is receiving an organ transplant other than a kidney. - Donor organ with a cold ischemic time > 48 hours. - ABO incompatible donor kidney. - Recipients of T cell, or B cell crossmatch positive transplant. - Panel reactive antibody (PRA) >30% - HIV or Hepatitis C virus, or Hepatitis B virus antigenemia. - Current malignancy or a history of malignancy - Liver disease - Uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or an active peptic ulcer - Use of warfarin, fluvastatin, or herbal supplements during the study. - Use of astemizole, pimozide, cisapride, terfenadine, or ketoconazole. - Hypersensitivity to thymoglobulin, IL-2 receptor inhibitor monoclonal antibodies, tacrolimus, everolimus, MPA, or corticosteroids. - Pregnant or lactating. - Abnormal screening/baseline labs WBC, platelet count, triglycerides, and cholesterol Double kidneys,ECD, pediatric en-block, and donation after cardiac death (DCD) |
Резултат
Първични изходни мерки
1. BPAR (Biopsy-proven Acute Rejection) Incidence During the First 12 Months Post-transplant [1 year]
Вторични изходни мерки
1. Incidence of Chronic Allograft Nephropathy (CAI) at 12 Months Post-transplant [1 year]
2. Graft Loss (Return to Permanent Dialysis or Death) [during the first 12 months post-transplant]
3. eGFR (Calculated Glomerular Filtration Rate), i.e., Renal Function, at 1 Month Post-transplant. [at 1 month post-transplant]
4. eGFR (Renal Function) at Month 3 Post-transplant [at 3 months post-transplant]
5. eGFR (Renal Function) at 6 Months Post-transplant [at 6 months post-transplant]
6. Discontinuance of Any Study Medication (Tacrolimus, Everolimus, or EC-MPS) [during the first 12 months post-transplant]
