DIabetic Retinopathy Candesartan Trials.

NCT00252720 | Completed Phase 3 Results

• 3 other identifiers: D2453C00046DIRECTSH-AHM-0046
• Study Type: interventional
• Target: 1,850
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

Diabetes mellitus type 1

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) Severity Scale

  Retinopathy progression was defined as the first occurrence of at least a 3-step increase in the ETDRS severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11). A generlized 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 (3)

• Number of Participants With a Regression of Diabetic Retinopathy.

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

• Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).

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

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

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

Study Arms (2)

candesartan

EXPERIMENTAL

candesartan cilexetil 32 mg once daily

Drug: candesartan

placebo

NO INTERVENTION

control

Interventions

candesartan DRUG

32 mg oral tablet

Also known as: ATACAND

candesartan

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Takeda: collaborator

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: 38682786 DERIVED

• 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: 21309844 DERIVED

• 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: 21225239 DERIVED

• 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: 19451554 DERIVED

• 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: 18823656 DERIVED

Related Links

• Related Info
• CSR-D2453C00046.pdf

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

candesartan; candesartan cilexetil

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune 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: August 1, 2001
• Primary Completion: February 1, 2008
• Study Completion: April 1, 2008
• Last Updated: June 3, 2014
• Results First Posted: June 3, 2014

Record last verified: 2014-04