Clinical trial NCT00252694: DIabetic Retinopathy Candesartan Trials
Official title: Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 2 Diabetic Patients With Retinopathy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: Diabetes mellitus type 2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2005-11-15
Enrollment: 4717
Sex: ALL
Minimum age (years): 37
Maximum age (years): 75
Standard ages: ADULT
OLDER_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 progression of diabetic retinopathy in normoalbuminuric type 2 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 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 1 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:

* Male or female aged 37 - 75 years with type 2 diabetes diagnosed at age of 36 years or thereafter.
* 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 and mean sitting DBP \< 85 or treated resting mean SBP \< 160 mmHg and mean sitting DBP \< 90 mmHg 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 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 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

Primary outcomes:
measure: Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) 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: Number of Participants With at Least a 3 Step Improvement or a Persistent 2-step Improvement in the ETDRS Severity Scale.
timeFrame: From baseline to end of study, i.e. 5 years.
measure: Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).
timeFrame: From baseline to end of study, i.e. 5 years.
measure: Rate of Change in Urinary Albumin Excretion Rate (UAER).
timeFrame: From Baseline to end of study, i.e. 5 years.
Other outcomes:
Locations:
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Atacand Medical Science Director, MD
role: STUDY_DIRECTOR
References:
citation: Tillin T, Orchard T, Malm A, Fuller J, Chaturvedi N. The role of antihypertensive therapy in reducing vascular complications of type 2 diabetes. Findings from the DIabetic REtinopathy Candesartan Trials-Protect 2 study. J Hypertens. 2011 Jul;29(7):1457-62. doi: 10.1097/HJH.0b013e3283480db9.
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: Sjolie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, Bilous R, Chaturvedi N; DIRECT Programme Study Group. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet. 2008 Oct 18;372(9647):1385-93. doi: 10.1016/S0140-6736(08)61411-7. Epub 2008 Sep 25.