DIabetic Retinopathy Candesartan Trials. - Full Text View

Sponsor:	AstraZeneca
Collaborator:	Takeda Global Research & Development Center, Inc.
Information provided by (Responsible Party):	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00252720

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes	Drug: Candesartan Cilexetil	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	DIRECT: DIabetic Retinopathy Candesartan Trials. Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients With Retinopathy.

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Type 1 Diabetic Eye Problems Retinal Disorders

Drug Information available for: CV 11974 Candesartan cilexetil

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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. [ Time Frame: Assessed at the end of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The rate of change in mean urinary albumin excretion rate (UAER) [ Time Frame: Assessed from baseline to the end of the study. ] [ Designated as safety issue: No ]

Enrollment:	1850
Study Start Date:	August 2001
Study Completion Date:	April 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: 1 Placebo
Experimental: 2 Candesartan cilexetil	Drug: Candesartan Cilexetil 32 mg oral tablet Other Name: ATACAND

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00252720

Sponsors and Collaborators

AstraZeneca

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

AstraZeneca Atacand Medical Science Director, MD

AstraZeneca

More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sjølie 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.

Porta M, Hainer JW, Jansson SO, Malm A, Bilous R, Chaturvedi N, Fuller JH, Klein R, Orchard T, Parving HH, Sjølie 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. Epub 2011 Jan 12.

Bilous R, Chaturvedi N, Sjølie 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. Epub 2009 May 18.

Chaturvedi N, Porta M, Klein R, Orchard T, Fuller J, Parving HH, Bilous R, Sjølie 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. Epub 2008 Sep 25.

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00252720 History of Changes
Other Study ID Numbers:	D2453C00046, DIRECT, SH-AHM-0046
Study First Received:	November 10, 2005
Last Updated:	August 29, 2011
Health Authority:	Denmark: Danish Medicines Agency

Keywords provided by AstraZeneca:

Diabetes mellitus type 1

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetic Retinopathy
Retinal Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases

Cardiovascular Diseases
Diabetes Complications
Candesartan cilexetil
Candesartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012