DIabetic Retinopathy Candesartan Trials.

AstraZeneca1,850 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,850

Conditions

Type 1 Diabetes

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

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.

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 a Regression of Diabetic Retinopathy.

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).

Time frame: From baseline to the end of the 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-randimisation, yearly assessments) for each patient

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