DIabetic Retinopathy Candesartan Trials.

Type 1 Diabetes Clinical Trial

— DIRECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00252720
• Other study ID #: D2453C00046
• Secondary ID: DIRECTSH-AHM-004
• Status: Completed
• Phase: Phase 3
• First received: November 10, 2005
• Last updated: May 9, 2014
• Start date: August 2001
• Est. completion date: April 2008

Study information

• Verified date: April 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1850
• Est. completion date: April 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases
• Type 1 Diabetes

Intervention

Drug:
• candesartan
32 mg oral tablet

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) Severity Scale	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.	From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.	No
Secondary	Number of Participants With a Regression of Diabetic Retinopathy.	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).	From baseline to the end of the study, i.e., 5 years	No
Secondary	Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).	Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.	From baseline to end of study, i.e. 5 years.	No
Secondary	Rate of Change in Urinary Albumin Excretion Rate (UAER).	An estimate of the slope from fitting a linear regression of log (UAER) over time (post-randimisation, yearly assessments) for each patient	From baseline to end of study, i.e. 5 years.	No

External Links

•   Link
•   CSR-D2453C00046.pdf