PROSPECTIVE MULTICENTER RANDOMIZED TRIAL TO COMPARE INCIDENCE OF NEW ONSET DIABETES MELLITUS AND GLUCOSE METABOLISM IN PATIENTS RECEIVING CYCLOSPORINE MICROEMULSION VERSUS TACROLIMUS AFTER DE NOVO KIDNEY TRANSPLANTATION

Abstract

O362 Aims: New Onset Diabetes Mellitus (NODM) after transplantation leads to an increased risk of cardiovascular complications and mortality. Based on clinical trials studying either tacrolimus (tac) or cyclosporine microemulsion (CsA–ME), it seems that tacrolimus is more diabetogenic but the difference between both drugs is difficult to assess as the definition of diabetes differed from one trial to the other. Furthermore, the potential impact of both drugs on glucose control in patients with pre-existing diabetes is unknown. This study compares the impact of CsA–ME and tac on glucose metabolism in de novo kidney transplant recipients. The efficacy of both drugs in the prevention of graft rejection is also assessed. Methods: This is a 6 months prospective randomized trial conducted in 700 patients from Australia, Canada, Japan, the US and 13 European countries. At transplant, patients are stratified according to diabetes status and ethnicity (diabetic, non-diabetic and Caucasian, non-diabetic and non-Caucasian) and then randomized 1:1 to receive either CsA–ME or tac within 24hours post transplant (table 1) as part of a quadruple immunosuppressive regimen comprising basiliximab, MMF or EC-MPA and steroids (table 2). At 3 and 6 months an oral glucose tolerance test (OGTT) is performed, HbA1c, consumption of anti-diabetic drugs and incidence of biopsy proven acute rejection (BPAR), graft loss and death are assessed.FigureTable 2 SteroidsFigureTable 1 Starting dose (mg/kg/day) and target blood levels (ng/mL) Results: We report the results from a planned interim analysis performed on the data provided by 117 patients enrolled between November 03 and March 04 and who will have reached 3 months post-transplant by July 04. 61 were randomized to CsA ME and 56 to tac. The number of diabetic, non-diabetic and Caucasian, non-diabetic and non-Caucasian was respectively 16, 93 and 8. The following data will be available for presentation at the ISOT 2004 meeting: Demographics and transplant characteristics; doses of immunosuppressants received; blood levels achieved; number of patients with NODM, impaired fasting glucose or impaired glucose tolerance at 3 months post transplant diagnosed according to the criteria recommended by the American Diabetes Association (ADA) and the World Health Organization (WHO). Mean HbA1c and serum creatinine at baseline and 3 months; number of BPAR, graft loss or death at 3 months. Conclusions: This interim analysis will provide the first multicenter estimation of the incidence of NODM as assessed by an OGTT and will also assess compliance with the immunosuppressive regimen recommended by the protocol (dose given and when appropriate blood levels achieved) and whether any safety or efficacy issues have been observed.