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Diabetic Retinopathy Candesartan Trials (DIRECT)

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
candesartan cilexetil
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Diabetes Mellitus, Insulin-Dependent

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 < 15 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 10/10 (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 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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

1

2

Arm Description

Placebo

candesartan cilexetil

Outcomes

Primary Outcome Measures

Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale.
Two steps were defined as either a 1-step change in each eye or as a 2-step change in one eye only. ETDRS is a scale with 11 steps (1-11, where a score of 1 represents no retinopathy and a score of 11 represents proliferative retinopathy). A generalized log-rank test was used to test difference between treatments.

Secondary Outcome Measures

Rate of Change in Urinary Albumin Excretion Rate (UAER).
An estimate of the slope from fitting a linear regression of log(UAER) over time for each patient.

Full Information

First Posted
November 10, 2005
Last Updated
May 9, 2014
Sponsor
AstraZeneca
Collaborators
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT00252733
Brief Title
Diabetic Retinopathy Candesartan Trials
Acronym
DIRECT
Official Title
Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients Without Retinopathy.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
June 2001 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Takeda

4. Oversight

5. Study Description

Brief Summary
The primary objective is to determine whether candesartan, compared to placebo reduces the incidence of diabetic retinopathy in normotensive, normoalbuminuric type 1 diabetic patients without retinopathy. The secondary objective is to determine whether candesartan, compared to placebo, beneficially influences the rate of change in urinary albumin excretion rate (UAER). This study is part of the DIRECT Programme also including secondary prevention studies of diabetic retinopathy in both type 1 and 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Diabetes Mellitus, Insulin-Dependent

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5238 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
No Intervention
Arm Description
Placebo
Arm Title
2
Arm Type
Experimental
Arm Description
candesartan cilexetil
Intervention Type
Drug
Intervention Name(s)
candesartan cilexetil
Other Intervention Name(s)
ATACAND
Intervention Description
32 mg once daily oral tablet given over 60 months
Primary Outcome Measure Information:
Title
Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale.
Description
Two steps were defined as either a 1-step change in each eye or as a 2-step change in one eye only. ETDRS is a scale with 11 steps (1-11, where a score of 1 represents no retinopathy and a score of 11 represents proliferative retinopathy). A generalized log-rank test was used to test difference between treatments.
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.
Secondary Outcome Measure Information:
Title
Rate of Change in Urinary Albumin Excretion Rate (UAER).
Description
An estimate of the slope from fitting a linear regression of log(UAER) over time for each patient.
Time Frame
From baseline to end of study, i.e. 5 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 < 15 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 10/10 (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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AstraZeneca Atacand Medical Science Director, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Herston
Country
Australia
Facility Name
Research Site
City
Perth
Country
Australia
Facility Name
Research Site
City
Odense
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
21309844
Citation
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.
Results Reference
derived
PubMed Identifier
21225239
Citation
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.
Results Reference
derived
PubMed Identifier
19451554
Citation
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.
Results Reference
derived
PubMed Identifier
18823656
Citation
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.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=308&filename=CSR-D2453C00045.pdf
Description
Related Info
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=308&filename=CSR-D2453C00045.pdf
Description
CSR-D2453C00045.pdf

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Diabetic Retinopathy Candesartan Trials

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