DIabetic Retinopathy Candesartan Trials

AstraZeneca4,717 enrolled

Overview

The primary objective is to determine whether candesartan, compared to placebo reduces the progression of diabetic retinopathy in normoalbuminuric type 2 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 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 1 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

4,717

Conditions

Type 2 Diabetes

Interventions

Eligibility

Sex: ALLMin age: 37 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female aged 37 - 75 years with type 2 diabetes diagnosed at age of 36 years or thereafter. * 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 and mean sitting DBP \< 85 or treated resting mean SBP \< 160 mmHg and mean sitting DBP \< 90 mmHg 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 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 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

Outcomes

Primary Outcomes

Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) 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.

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

Number of Participants With at Least a 3 Step Improvement or a Persistent 2-step Improvement 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).

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

Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).

Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.

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

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

An estimate of the slope from fitting a linear regression of log(UAER) over time (post-randomisation, yearly assessments) for each patient.

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