Diabetic Retinopathy Candesartan Trials

AstraZeneca5,238 enrolled

Overview

The primary objective is to determine whether candesartan, compared to placebo reduces the incidence of diabetic retinopathy in normotensive, normoalbuminuric type 1 diabetic patients without retinopathy. The secondary objective is to determine whether candesartan, compared to placebo, beneficially influences the rate of change in urinary albumin excretion rate (UAER). This study is part of the DIRECT Programme also including secondary prevention studies of diabetic retinopathy in both type 1 and type 2 diabetes. The primary objective for all three pooled studies is to determine whether candesartan, compared to placebo, reduces the incidence of microalbuminuria in type 1 and type 2 diabetic patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

5,238

Conditions

Type 1 Diabetes

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Type 1 diabetes diagnosed before age of 36 years and in need for continuous insulin treatment within 1 year of diagnosis of diabetes are included. * Duration of diabetes for \> 1 year and \< 15 years with stable diabetic therapy within last 6 months. * Patients with untreated resting mean sitting SBP \< 130 mmHg, mean sitting DBP \< 85 mmHg and with retinal photograph grading level 10/10 (on ETDRS severity scale). Exclusion Criteria: * Patients with the following conditions are excluded from participation in the study: * Cataract or media opacity of a degree which precludes taking gradable retinal photographs * Angle closure glaucoma, which precludes pharmacological dilatation of the pupil * History of retinopathy * History or presence of clinical significant macular oedema (CSME) * History or evidence of photocoagulation of the retina Other retinal conditions which may mask assessment, eg, retinal vein occlusion * Positive micral dipstick test * Presence of secondary diabetes * Pregnant or lactating women or women of child bearing potential not practicing an adequate method of contraception * Need of treatment with ACE-inhibitor * Haemodynamically significant aortic or mitral valve stenosis * Known renal artery stenosis or kidney transplantation * Hypersensitivity to study drug * Severe concomitant disease which may interfere with the assessment of the patient, eg, malignancy, as judged by the investigator

Locations (3)

Research Site

Herston, Australia

Research Site

Perth, Australia

Research Site

Odense, Denmark

Outcomes

Primary Outcomes

Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale.

Two steps were defined as either a 1-step change in each eye or as a 2-step change in one eye only. ETDRS is a scale with 11 steps (1-11, where a score of 1 represents no retinopathy and a score of 11 represents proliferative retinopathy). A generalized log-rank test was used to test difference between treatments.

Time frame: From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.

Secondary Outcomes

Rate of Change in Urinary Albumin Excretion Rate (UAER).

An estimate of the slope from fitting a linear regression of log(UAER) over time for each patient.

Time frame: From baseline to end of study, i.e. 5 years.