DIabetic Retinopathy Candesartan Trials. (DIRECT)

This study has been completed.
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00252720
First received: November 10, 2005
Last updated: May 9, 2014
Last verified: April 2014

November 10, 2005
May 9, 2014
August 2001
February 2008   (final data collection date for primary outcome measure)
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 ]
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.
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.
Complete list of historical versions of study NCT00252720 on ClinicalTrials.gov Archive Site
  • Number of Participants With a Regression of Diabetic Retinopathy. [ Time Frame: From baseline to the end of the study, i.e., 5 years ] [ Designated as safety issue: No ]
    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. ] [ 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-randimisation, yearly assessments) for each patient
The rate of change in mean urinary albumin excretion rate (UAER) from baseline to the end of the study.
Not Provided
Not Provided
 
DIabetic Retinopathy Candesartan Trials.
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Type 1 Diabetes
Drug: candesartan
32 mg oral tablet
Other Name: ATACAND
  • Experimental: candesartan
    candesartan cilexetil 32 mg once daily
    Intervention: Drug: candesartan
  • No Intervention: placebo
    control

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1850
April 2008
February 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00252720
D2453C00046, DIRECT, SH-AHM-0046
Not Provided
AstraZeneca
AstraZeneca
Takeda
Study Director: AstraZeneca Atacand Medical Science Director, MD AstraZeneca
AstraZeneca
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP