Clinical trial NCT00252733: Diabetic Retinopathy Candesartan Trials
Official title: Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients Without Retinopathy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes
Keywords: Diabetes Mellitus, Insulin-Dependent
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2005-11-15
Enrollment: 5238
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale.
timeFrame: 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:
measure: Rate of Change in Urinary Albumin Excretion Rate (UAER).
timeFrame: From baseline to end of study, i.e. 5 years.
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Research Site
city: Perth
country: Australia
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Atacand Medical Science Director, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.