Diabetic Retinopathy Candesartan Trials

Phase 3

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
2	candesartan cilexetil	candesartan cilexetil

Primary Outcome Measures

Name	Time	Method
Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale.	From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.	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.

Secondary Outcome Measures

Name	Time	Method
Rate of Change in Urinary Albumin Excretion Rate (UAER).	From baseline to end of study, i.e. 5 years.	An estimate of the slope from fitting a linear regression of log(UAER) over time for each patient.