The DIabetic Retinopathy Candesartan Trials (DIRECT) Programme, rationale and study design

The DIabetic Retinopathy Candesartan Trials (DIRECT) Programme consists of three randomised, double-masked, parallel, placebo-controlled studies to determine the impact of treatment with candesartan on diabetic retinopathy. In Type 1 diabetes, 1,700 patients without retinopathy will be randomised into a primary prevention study, and 1,200 with non-proliferative retinopathy into a secondary prevention study. In Type 2 diabetes, 1,600 patients with non-proliferative retinopathy will be randomised. Patients will be followed for at least three years. Eligible patients must be normotensive (systolic blood pressure [SBP] ≤ 130 mmHg and diastolic blood pressure [DBP] ≤ 85 mmHg) without antihypertensive medication in Type 1 diabetes, and either normotensive or treated hypertensive (SBP ≤ 160 mmHg and SBP ≤ 90 mmHg) and not taking angiotensin-converting enzyme inhibitors or AT 1 receptor blockers in Type 2 diabetes. All patients will be normoalbuminuric, based on two overnight urine collections. The primary endpoint is based upon retinal photographs, graded to the Early Treatment of Diabetic Retinopathy Study scale. A two-step increase on this scale defines incidence, and a three-step increase defines progression of retinopathy. The main secondary endpoint for each study is change in urinary albumin excretion rate. A positive outcome of the DIRECT Programme would be an important step forward in the clinical management of patients with diabetes.