Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial (ORIENT): Rationale and Study Design

Abstract

Diabetic nephropathy (DN) is a leading cause of endstage renal disease (ESRD) in Japan and Hong Kong. Asian patients are known to be more predisposed to DN and ESRD than Caucasians. Strict blood glucose and blood pressure control are key factors in prevention and treatment of DN. In the last decade, inhibition of the renin-angiotensin-aldosterone (RAA) system has been confirmed to reduce the incidence of cardiovascular complications in Caucasian patients with diabetes. Although the RENAAL study has demonstrated the beneficial effects of inhibition of the RAA system on prevention of ESRD and death in type 2 diabetic patients with overt proteinuria, only 17% of patients in this multicenter study were of Asian ethnicity. Given the predilection of Asian diabetic patients for renal complications and the rising burden of ESRD, there is a need to confirm these findings in a homogenous group of Asian patients. The ORIENT (Omesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial) is a randomized, double-blind, placebo-controlled study in Japan and Hong Kong to evaluate the renal protective benefits of olmesartan medoxomil in type 2 diabetic patients with overt proteinuria (urinary albumin to creatinine ratio > or =300 mg/g creatinine) and renal insufficiency (serum creatinine: 1.0-2.5 mg/dl). The study has a targeted enrollment of 400 Japanese and Hong Kong Chinese patients. The primary outcome is the composite endpoint of time to the first occurrence of doubling of serum creatinine, ESRD (serum creatinine more than 5.0 mg/dl, the need for chronic dialysis, or renal transplantation) or death. The average follow-up period is 4 years and the study ends in 2009.