DIabetic Retinopathy Candesartan Trials.

Study Overview
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Brief Summary
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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.

Official Title
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DIRECT: DIabetic Retinopathy Candesartan Trials. Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients With Retinopathy.

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: candesartan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: candesartan<br>candesartan cilexetil 32 mg once daily | Drug: candesartan<br>* 32 mg oral tablet<br>* Other names: ATACAND;|
| No Intervention: placebo<br>control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | 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 | From baseline to end of study, i.e. 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus type 1