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DIabetic Retinopathy Candesartan Trials. (DIRECT)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00252720
First Posted: November 15, 2005
Last Update Posted: June 3, 2014
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.
Collaborator:
Takeda
Information provided by (Responsible Party):
AstraZeneca
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes Drug: candesartan Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: DIRECT: DIabetic Retinopathy Candesartan Trials. Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients With Retinopathy.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) 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. ]
    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.


Secondary Outcome Measures:
  • Number of Participants With a Regression of Diabetic Retinopathy. [ Time Frame: From baseline to the end of the study, i.e., 5 years ]
    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).

  • Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR). [ Time Frame: From baseline to end of study, i.e. 5 years. ]
    Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.

  • 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 (post-randimisation, yearly assessments) for each patient


Enrollment: 1850
Study Start Date: August 2001
Study Completion Date: April 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: candesartan
candesartan cilexetil 32 mg once daily
Drug: candesartan
32 mg oral tablet
Other Name: ATACAND
No Intervention: placebo
control

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00252720


Sponsors and Collaborators
AstraZeneca
Takeda
Investigators
Study Director: AstraZeneca Atacand Medical Science Director, MD AstraZeneca
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00252720     History of Changes
Other Study ID Numbers: D2453C00046
DIRECT
SH-AHM-0046
First Submitted: November 10, 2005
First Posted: November 15, 2005
Results First Submitted: March 19, 2012
Results First Posted: June 3, 2014
Last Update Posted: June 3, 2014
Last Verified: April 2014

Keywords provided by AstraZeneca:
Diabetes mellitus type 1

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Retinal Diseases
Diabetic Retinopathy
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Candesartan
Candesartan cilexetil
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action