DIabetic Retinopathy Candesartan Trials (DIRECT)

This study has been completed.
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00252694
First received: November 10, 2005
Last updated: May 9, 2014
Last verified: April 2014
  Purpose

The primary objective is to determine whether candesartan, compared to placebo reduces the progression of diabetic retinopathy in normoalbuminuric type 2 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 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 1 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 2 Diabetes
Drug: candesartan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 2 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. ] [ Designated as safety issue: No ]
    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 at Least a 3 Step Improvement or a Persistent 2-step Improvement in the ETDRS Severity Scale. [ Time Frame: From baseline to end of study, i.e. 5 years. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    An estimate of the slope from fitting a linear regression of log(UAER) over time (post-randomisation, yearly assessments) for each patient.


Enrollment: 4717
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

Ages Eligible for Study:   37 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged 37 - 75 years with type 2 diabetes diagnosed at age of 36 years or thereafter.
  • 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 and mean sitting DBP < 85 or treated resting mean SBP < 160 mmHg and mean sitting DBP < 90 mmHg 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 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 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00252694

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

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00252694     History of Changes
Other Study ID Numbers: D2453C00047, DIRECT, SH-AHM-0047
Study First Received: November 10, 2005
Results First Received: March 22, 2012
Last Updated: May 9, 2014
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by AstraZeneca:
Diabetes mellitus type 2

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Retinal Diseases
Diabetic Retinopathy
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Candesartan
Candesartan cilexetil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014