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DIabetic Retinopathy Candesartan Trials. (DIRECT)

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
candesartan
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Diabetes mellitus type 1

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    candesartan

    placebo

    Arm Description

    candesartan cilexetil 32 mg once daily

    control

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Number of Participants With a Regression of Diabetic Retinopathy.
    Regression of diabetic retinopathy was defined as at least a 3 step improvement or a persistent 2-step improvement (confirmed in 2 consecutive photography sets) in the Early Treatment of Diabetic Retinopathy Study (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).
    Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).
    Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.
    Rate of Change in Urinary Albumin Excretion Rate (UAER).
    An estimate of the slope from fitting a linear regression of log (UAER) over time (post-randimisation, yearly assessments) for each patient

    Full Information

    First Posted
    November 10, 2005
    Last Updated
    May 9, 2014
    Sponsor
    AstraZeneca
    Collaborators
    Takeda
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00252720
    Brief Title
    DIabetic Retinopathy Candesartan Trials.
    Acronym
    DIRECT
    Official Title
    DIRECT: DIabetic Retinopathy Candesartan Trials. Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients With Retinopathy.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2014
    Overall Recruitment Status
    Completed
    Study Start Date
    August 2001 (undefined)
    Primary Completion Date
    February 2008 (Actual)
    Study Completion Date
    April 2008 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AstraZeneca
    Collaborators
    Takeda

    4. Oversight

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 1 Diabetes
    Keywords
    Diabetes mellitus type 1

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    1850 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    candesartan
    Arm Type
    Experimental
    Arm Description
    candesartan cilexetil 32 mg once daily
    Arm Title
    placebo
    Arm Type
    No Intervention
    Arm Description
    control
    Intervention Type
    Drug
    Intervention Name(s)
    candesartan
    Other Intervention Name(s)
    ATACAND
    Intervention Description
    32 mg oral tablet
    Primary Outcome Measure Information:
    Title
    Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) Severity Scale
    Description
    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.
    Time Frame
    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 Outcome Measure Information:
    Title
    Number of Participants With a Regression of Diabetic Retinopathy.
    Description
    Regression of diabetic retinopathy was defined as at least a 3 step improvement or a persistent 2-step improvement (confirmed in 2 consecutive photography sets) in the Early Treatment of Diabetic Retinopathy Study (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).
    Time Frame
    From baseline to the end of the study, i.e., 5 years
    Title
    Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).
    Description
    Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.
    Time Frame
    From baseline to end of study, i.e. 5 years.
    Title
    Rate of Change in Urinary Albumin Excretion Rate (UAER).
    Description
    An estimate of the slope from fitting a linear regression of log (UAER) over time (post-randimisation, yearly assessments) for each patient
    Time Frame
    From baseline to end of study, i.e. 5 years.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    AstraZeneca Atacand Medical Science Director, MD
    Organizational Affiliation
    AstraZeneca
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    21309844
    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.
    Results Reference
    derived
    PubMed Identifier
    21225239
    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.
    Results Reference
    derived
    PubMed Identifier
    19451554
    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.
    Results Reference
    derived
    PubMed Identifier
    18823656
    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.
    Results Reference
    derived
    Links:
    URL
    http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=1268&filename=CSR-D2453C00046.pdf
    Description
    Related Info
    URL
    http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=1268&filename=CSR-D2453C00046.pdf
    Description
    CSR-D2453C00046.pdf

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    DIabetic Retinopathy Candesartan Trials.

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