DIabetic Retinopathy Candesartan Trials.

Phase 3

Completed

Brief Summary: The primary objective is to determine whether candesartan, compared to placebo reduces the progression of diabetic retinopathy in normotensive, normoalbuminuric type 1 diabetic patients with retinopathy.

The secondary objective is to determine whether candesartan, compared to placebo, reduces the incidence of clinically significant macular oedema (CSME) and/or proliferative diabetic retinopathy (PDR) and beneficially influences the rate of change in urinary albumin excretion rate (UAER).

This study is part of the DIRECT Programme also including a primary prevention study of diabetic retinopathy in type 1 diabetes and a secondary prevention study in 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

Male or female aged 18 - 55 years with 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 < 20 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 > 20/10 up to < 47/47 (on ETDRS severity scale).

Exclusion Criteria

Patients with the following conditions are excluded from participation on 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 or presence of proliferative 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
candesartan	candesartan	candesartan cilexetil 32 mg once daily

Primary Outcome Measures

Name	Time	Method
Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) 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.	Retinopathy progression was defined as the first occurrence of at least a 3-step increase in the ETDRS severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11). A generlized log-rank test was used to test difference between treatments.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Regression of Diabetic Retinopathy.	From baseline to the end of the study, i.e., 5 years	Regression of diabetic retinopathy was defined as at least a 3 step improvement or a persistent 2-step improvement (confirmed in 2 consecutive photography sets) in the Early Treatment of Diabetic Retinopathy Study (ETDRS) severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11).
Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).	From baseline to end of study, i.e. 5 years.	Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.
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 (post-randimisation, yearly assessments) for each patient