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

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

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: February 2008

Intervention(s) in this Clinical Trial

• Drug: Candesartan Cilexetil
  • 32 mg oral tablet

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: 1
  • Placebo
• Experimental: 2
  • Candesartan cilexetil

Primary Measures

• Progression of diabetic retinopathy is a change from baseline to any retinal photograph taken after the randomization visit by at least 3 steps in the ETDRS severity scale.
  • Time Frame: Assessed at the end of the study
    Safety Issue?: No

Secondary Measures

• The rate of change in mean urinary albumin excretion rate (UAER)
  • Time Frame: Assessed from baseline to the end of the study.
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: AstraZeneca

Overall Clinical Trial Officials and Contacts

AstraZeneca Atacand Medical Science Director, MD Study Director AstraZeneca  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00252720

Study ID Number: D2453C00046

ClinicalTrials.gov Identifier: NCT00252720

Health Authority: Denmark: Danish Medicines Agency