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Diabetic Retinopathy Candesartan Trials (DIRECT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00252733
Recruitment Status : Completed
First Posted : November 15, 2005
Results First Posted : April 13, 2012
Last Update Posted : May 14, 2014
Information provided by (Responsible Party):

Brief Summary:

The primary objective is to determine whether candesartan, compared to placebo reduces the incidence of diabetic retinopathy in normotensive, normoalbuminuric type 1 diabetic patients without retinopathy.

The secondary objective is to determine whether candesartan, compared to placebo, beneficially influences the rate of change in urinary albumin excretion rate (UAER).

This study is part of the DIRECT Programme also including secondary prevention studies of diabetic retinopathy in both type 1 and 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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: candesartan cilexetil Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5238 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients Without Retinopathy.
Study Start Date : June 2001
Actual Primary Completion Date : April 2008
Actual Study Completion Date : April 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
No Intervention: 1
Experimental: 2
candesartan cilexetil
Drug: candesartan cilexetil
32 mg once daily oral tablet given over 60 months
Other Name: ATACAND

Primary Outcome Measures :
  1. Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale. [ 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. ]
    Two steps were defined as either a 1-step change in each eye or as a 2-step change in one eye only. ETDRS is a scale with 11 steps (1-11, where a score of 1 represents no retinopathy and a score of 11 represents proliferative retinopathy). A generalized log-rank test was used to test difference between treatments.

Secondary Outcome Measures :
  1. Rate of Change in Urinary Albumin Excretion Rate (UAER). [ Time Frame: 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 for each patient.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 < 15 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 10/10 (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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00252733

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Research Site
Herston, Australia
Research Site
Perth, Australia
Research Site
Odense, Denmark
Sponsors and Collaborators
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Study Director: AstraZeneca Atacand Medical Science Director, MD AstraZeneca

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: AstraZeneca Identifier: NCT00252733    
Other Study ID Numbers: D2453C00045
First Posted: November 15, 2005    Key Record Dates
Results First Posted: April 13, 2012
Last Update Posted: May 14, 2014
Last Verified: April 2014
Keywords provided by AstraZeneca:
Diabetes Mellitus, Insulin-Dependent
Additional relevant MeSH terms:
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Retinal Diseases
Diabetic Retinopathy
Diabetes Mellitus
Endocrine System Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Candesartan cilexetil
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action