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

Phase 4

Terminated

• Conditions: Diabetes Mellitus, Adult-Onset
• Interventions: Drug: Tacrolimus with rapid steroid withdrawal; Drug: Tacrolimus with steroids minimization; Drug: CsA with steroid minimization

• Registration Number: NCT01002339
• Lead Sponsor: Armando Torres Ramírez

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2009-10-26
• Study First Submitted QC: 2009-10-26
• Study First Posted: 2009-10-27
• Study Start: 2010-02
• Primary Completion: 2014-02
• Study Completion: 2015-06
• Results First Submitted: 2016-02-05
• Results First Submitted QC: 2016-06-21
• Results First Posted: 2016-08-03
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-28
• Last Update Posted: 2024-10-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 134

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tacrolimus with rapid steroid withdrawal	Tacrolimus with rapid steroid withdrawal	Basiliximab induction. Tacrolimus plus Mycophenolate mofetil (MMF), and corticosteroids with rapid withdrawal after one week.
Tacrolimus with steroids minimization	Tacrolimus with steroids minimization	Basiliximab induction.Tacrolimus plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal
CsA with steroid minimization	CsA with steroid minimization	Basiliximab induction. Ciclosporin A (CsA) plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal

Primary Outcome Measures

Name	Time	Method
Patients Treated With Insulin or Oral Antidiabetic Drugs	1 year
Primary Outcome Measure "New Onset Diabetes After Renal Transplantation" (NODAT)	1 year	American Diabetes Association criteria (ADA) including an oral glucose tolerance test.
Primary Outcome Measure (Glucose Intolerance)	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Renal Function	1 year	Estimated Glomerular Filtration Rate (ml/min/1.73 m\^2)
Number of Antihypertensive Drugs Patients Reported Taking.	1 year
Lipidic Profile (LDL-c)	1 year
Percentage of Patients Using Statins	1 year
Percentage of Patients Using Acetylsalicylic Acid (ASA)	1 year
Rejection	1 year	Biopsy proven acute rejection. Measured variable: Rate of Biopsy proven acute rejection.
Blood Pressure	1 year	Diastolic pressure (mmHg)
Proteinuria	1 year
Lipidic Profile (Cholesterol)	1 year	Lipidic Profile (total cholesterol)
Lipidic Profile (HDL-c)	1 year
Lipidic Profile (Triglycerides)	1 year
Changes of Carotid Intima-media Thickness Over Time	1 year	absolute difference between carotid intima-media thickness at study end versus baseline.

Trial Locations

Locations (10)

Antonio Osuna; 🇪🇸 Granada, Andalucía, Spain

Domingo Hernández; 🇪🇸 Málaga, Andalucía, Spain

Carmen Díaz Corte; 🇪🇸 Oviedo, Asturias, Spain

Carlos Gómez Alamillo; 🇪🇸 Santander, Cantabria, Spain

Juan Manuel Díaz; 🇪🇸 Barcelona, Cataluña, Spain

Francisco Moreso; 🇪🇸 Barcelona, Cataluña, Spain

Francisco Valdés; 🇪🇸 La Coruña, Galicia, Spain

Armando Torres Ramírez; 🇪🇸 La Laguna, S/C De Tenerife, Spain

Roberto Gallego; 🇪🇸 Las Palmas de Gran Canaria, Spain

Luis Pallardo; 🇪🇸 Valencia, Spain