Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation

Phase 4TerminatedNCT01002339

Armando Torres Ramírez134 enrolled

Overview

New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. Cyclosporine (CsA) and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, Tacrolimus increases 2 times the risk of NODAT as compared to CsA.

New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. CsA and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, increases 2 times the risk of NODAT as compared to CsA. Objectives: a) To compare the incidence of NODAT and glucose intolerance with 3 different regimes: Tacrolimus with rapid steroid withdrawal; Tacrolimus with steroids minimization; and CsA with steroid minimization; b) To compare acute rejection rate, renal function and graft and patient survival between different regimes; and c) to investigate the influence of different regimes on subclinical atheromatosis. A total of 210 patients will be randomized. The primary efficacy variable will be NODAT or glucose intolerance at 1 year; secondary efficacy variables will be acute rejection, renal function, and changes of carotid intima-media thickness over time.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

134

Conditions

Diabetes Mellitus, Adult-Onset

Interventions

Tacrolimus with rapid steroid withdrawalDRUG

* Basiliximab induction (4 mg i.v., days 0 and 4). * Corticosteroids: 0.5 gr of i.v. Methylprednisolone (MP) intraoperatively and 125 mg on the first day, followed by oral doses of prednisone rapidly tapered from 30 mg/day to complete discontinuation by postoperative day 7. * Tacrolimus: 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month and then 5-8 ng/ml. * Mycophenolate mofetil 1 gr b.i.d. for the first month and then 500 mg b.i.d.

Tacrolimus with steroids minimizationDRUG

* Basiliximab induction (4 mg i.v., days 0 an 4) * Corticosteroids: 0.5 gr of i.v. MP intraoperatively and 60 mg on the first day, followed by oral doses of prednisone starting with 0.3 mg/Kg/day, and gradual weekly tapering to complete discontinuation over 6 months. * Tacrolimus 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month and then 5-8 ng/ml. * Mycophenolate mofetil 1 gr b.i.d. for the first month and then 500 mg b.i.d.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Primary renal transplant recipients with end stage renal disease * No prior history of diabetes mellitus before transplant * Absence of Immunologic risk defined by the investigator criterion and Panel Reactive Antibody (PRA) \< 50% * Absence of severe infection and hepatitis C or B infection * Efficient contraception in women during the study Additionally must meet one of these "Metabolic Criteria * Recipient age \>or =60 or * Recipient age between 45 and 59 years and at least one of the following metabolic criteria: Prior to transplantation Triglycerides (TGS) \>200mg/dl or the combination of a body mass index (BMI)\> 27 and Triglycerides\>150 mg/dl or the combination of HDL-cholesterol\<40 mg/dl for men or \<50 mg/dl for women and Triglycerides \>150 mg/dl. Exclusion Criteria: * Patients with type I or II diabetes prior to transplantation defined by the American Diabetes Association (ADA) criteria * Recipient age under 45 * Patients receiving a second renal transplant * Patients with high immunological risk or PRA (panel reactive antibody level) \>or =50% * Severe infection or hepatitis C or B infection. * Dual renal transplant or double transplant with any other organ.

Locations (10)

Antonio Osuna

Granada, Andalusia, Spain

Domingo Hernández

Málaga, Andalusia, Spain

Carlos Gómez Alamillo

Santander, Cantabria, Spain

Juan Manuel Díaz

Barcelona, Catalonia, Spain

Outcomes

Primary Outcomes

Primary Outcome Measure "New Onset Diabetes After Renal Transplantation" (NODAT)

American Diabetes Association criteria (ADA) including an oral glucose tolerance test.

Time frame: 1 year

Patients Treated With Insulin or Oral Antidiabetic Drugs

Time frame: 1 year

Primary Outcome Measure (Glucose Intolerance)

Glycemia \>=140 and \<200 mg/dl, 2 hours after a standard oral glucose tolerance test. Measured values: glucose intolerance at 1 year defined by ADA criteria.

Time frame: 1 year

Secondary Outcomes

Rejection

Biopsy proven acute rejection. Measured variable: Rate of Biopsy proven acute rejection.

Time frame: 1 year

Renal Function

Estimated Glomerular Filtration Rate (ml/min/1.73 m\^2)

Time frame: 1 year

Proteinuria

Time frame: 1 year

Blood Pressure

Systolic pressure (mmHg)

Time frame: 1 year

Blood Pressure

Diastolic pressure (mmHg)

Time frame: 1 year

Number of Antihypertensive Drugs Patients Reported Taking.

Time frame: 1 year

Lipidic Profile (Triglycerides)

Data from ClinicalTrials.gov

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