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.
Chaturvedi
Nish
N
International Centre for Circulatory Health Department of Epidemiology and Public Health, Imperial College at St Mary's, London, W2 1PG, UK. n.chaturvedi@ic.ac.uk
Sjoelie
Anne Katrin
AK
Svensson
Anders
A
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D006973:Hypertension / Q000150:complications; D017063:Outcome Assessment, Health Care; D012107:Research Design; D018401:Sample Size; D013777:Tetrazoles / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan