- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00252720
DIabetic Retinopathy Candesartan Trials. (DIRECT)
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.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: candesartan
candesartan cilexetil 32 mg once daily
|
32 mg oral tablet
Other Names:
|
No Intervention: placebo
control
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
From baseline to the end of the study, i.e., 5 years
|
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.
|
From baseline to end of study, i.e. 5 years.
|
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
|
From baseline to end of study, i.e. 5 years.
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Sjolie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, Bilous R, Aldington S, Chaturvedi N. Retinal microaneurysm count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme. Diabet Med. 2011 Mar;28(3):345-51. doi: 10.1111/j.1464-5491.2010.03210.x.
- Porta M, Hainer JW, Jansson SO, Malm A, Bilous R, Chaturvedi N, Fuller JH, Klein R, Orchard T, Parving HH, Sjolie AK; DIRECT Study Group. Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled DIabetic REtinopathy Candesartan Trials. Diabetologia. 2011 Jun;54(6):1298-303. doi: 10.1007/s00125-010-2040-1. Epub 2011 Jan 12.
- Bilous R, Chaturvedi N, Sjolie AK, Fuller J, Klein R, Orchard T, Porta M, Parving HH. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med. 2009 Jul 7;151(1):11-20, W3-4. doi: 10.7326/0003-4819-151-1-200907070-00120. Epub 2009 May 18.
- Chaturvedi N, Porta M, Klein R, Orchard T, Fuller J, Parving HH, Bilous R, Sjolie AK; DIRECT Programme Study Group. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet. 2008 Oct 18;372(9647):1394-402. doi: 10.1016/S0140-6736(08)61412-9. Epub 2008 Sep 25.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Eye Diseases
- Endocrine System Diseases
- Diabetic Angiopathies
- Diabetes Complications
- Diabetes Mellitus
- Retinal Diseases
- Diabetic Retinopathy
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Candesartan
Other Study ID Numbers
- D2453C00046
- DIRECT
- SH-AHM-0046
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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