NCT00252733

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5,238

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jun 2001

Longer than P75 for phase_3

Geographic Reach
2 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2001

Completed
4.4 years until next milestone

First Submitted

Initial submission to the registry

November 10, 2005

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 15, 2005

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2008

Completed
4 years until next milestone

Results Posted

Study results publicly available

April 13, 2012

Completed
Last Updated

May 14, 2014

Status Verified

April 1, 2014

Enrollment Period

6.8 years

First QC Date

November 10, 2005

Results QC Date

March 31, 2009

Last Update Submit

May 9, 2014

Conditions

Type 1 Diabetes

Keywords

Diabetes Mellitus, Insulin-Dependent

Outcome Measures

Primary Outcomes (1)

  • 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.

    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 Outcomes (1)

  • Rate of Change in Urinary Albumin Excretion Rate (UAER).

    From baseline to end of study, i.e. 5 years.

Study Arms (2)

1

NO INTERVENTION

Placebo

2

EXPERIMENTAL

candesartan cilexetil

Drug: candesartan cilexetil

Interventions

candesartan cilexetilDRUG

32 mg once daily oral tablet given over 60 months

Also known as: ATACAND
2

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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).

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Research Site

Herston, Australia

Location

Research Site

Perth, Australia

Location

Research Site

Odense, Denmark

Location

Related Publications (5)

  • Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.

    PMID: 38682786DERIVED

  • 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.

    PMID: 21309844DERIVED

  • 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.

    PMID: 21225239DERIVED

  • 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.

    PMID: 19451554DERIVED

  • 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.

    PMID: 18823656DERIVED

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

candesartan cilexetil

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Niklas Berglind, GPS Atacand
Organization
AstraZeneca
ClinicalTrialTransparency@astrazeneca.com
+46 31 7766310

Study Officials

  • AstraZeneca Atacand Medical Science Director, MD

    AstraZeneca

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 10, 2005

First Posted

November 15, 2005

Study Start

June 1, 2001

Primary Completion

April 1, 2008

Study Completion

April 1, 2008

Last Updated

May 14, 2014

Results First Posted

April 13, 2012

Record last verified: 2014-04

Locations

AU(2)DK(1)