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Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema (REVEAL)

Primary Purpose

Diabetic Macular Edema

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ranibizumab
Laser photocoagulation
Sham ranibizumab
Sham laser photocoagulation
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring DME, Diabetic, macula, edema, ranibizumab, REVEAL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with Type 1 or Type 2 diabetes mellitus according to American Diabetes Association (ADA) or World Health Organization (WHO) guidelines with HbA1c not more than 10.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes.
  • Patients with visual impairment due to focal or diffuse Diabetic Macular Edema in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected for study treatment unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for study treatment.

  • The study eye must fulfill the following criteria at Visit 1:

    • Best-Corrected Visual Acuity (BCVA) score between 78 and 39 letters, inclusively, using Early Treatment of Diabetic Retinopathy (ETDRS) chart-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160).
    • Decrease in vision is due to DME and not due to other causes, in the opinion of the investigator.
    • Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study.

Exclusion Criteria:

  • Ocular concomitant conditions/ diseases:

    • Concomitant conditions in the study eye which could, in the opinion of the investigator, prevent the improvement of visual acuity on study treatment.
    • Active intraocular inflammation in either eye.
    • Any active infection in either eye.
    • History of uveitis in either eye.
    • Uncontrolled glaucoma in either eye.

  • Ocular treatments:

    • Panretinal laser photocoagulation in the study eye within 6 months prior to or during the study.
    • Focal/grid laser photocoagulation in the study eye within 3 months prior to study entry.

  • Systemic conditions or treatments:

    • History of stroke
    • Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine level > 2.0 mg/dL.
    • Untreated diabetes mellitus
    • Blood pressure systolic > 160 mmHg or diastolic > 100 mmHg

  • Compliance/ Administrative:

    • Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigational Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Adjunctive treatment

Monotherapy treatment

Laser control

Arm Description

Adjunctive administration of ranibizumab 0.5 mg intravitreal injections and active laser.

Monotherapy ranibizumab 0.5 mg intravitreal injections plus sham laser.

Active laser treatment plus sham intravitreal injections.

Outcomes

Primary Outcome Measures

Average Change From Baseline of Best-Corrected Visual Acuity (BCVA) Over 12 Months (From Month 1 to Month 12 Compared to Baseline)
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement.

Secondary Outcome Measures

Change From Baseline on Central Retinal Subfield Thickness (CRST) at Month 12
Central Retinal Subfield Thickness (CRST) was measured using Optical Coherence Tomography (OCT) in micrometers. A negative change from baseline of CRST indicates improvement.
Percent of Participants With Anatomical Changes in Intra-retinal Cysts at End of Study Compared to Baseline
Presence or absence of intra-retinal cysts in any of the 6 sections of the study eye was measured using Optical Coherence Tomography (OCT). A complete resolution or decrease from baseline of intra-retinal cysts indicates improvement.
Percent of Participants With Anatomical Changes in Sub-retinal Fluid at End of Study Compared to Baseline
Presence or absence of sub-retinal fluid in any of the 6 sections of the study eye was measured using Optical Coherence Tomography (OCT). A complete resolution or decrease from baseline of sub-retinal fluid indicates improvement.
Percent of Participants With Visual Acuity Above 73 Letters at Month 12
Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at month 12 indicates a positive outcome.
Percent of Participants Who Gained >= 10 Letters at Month 12 Compared to Baseline
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A gain of 10 or more BCVA letters from baseline indicates improvement. A BCVA of 84 letters or more at Month 12 indicates improvement.
Percent of Participants Who Lost >= 10 Letters at Month 12 Compared to Baseline
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A loss of 10 or more BCVA letters from baseline indicates worsening.
Percent of Participants Who Gained >= 15 Letters at Month 12 Compared to Baseline
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A gain of 15 or more BCVA letters from baseline indicates improvement. A BCVA of 84 letters or more at Month 12 indicates improvement.
Percent of Participants Who Lost >= 15 Letters at Month 12 Compared to Baseline
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A loss of 15 or more BCVA letters from baseline indicates worsening.
Best-Corrected Visual Acuity (BCVA) Mean Change From Baseline at Month 12
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.
Patient Outcome Measure Euro Quality of Life Questionnaire (EQ-5D)
The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Participants self-rate their health on a visual, vertical analogue scale from 0 to 100 where the endpoints are labeled "Best imaginable health state" (100) and "worst imaginable health state" (0).

Full Information

First Posted
October 2, 2009
Last Updated
September 18, 2012
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00989989
Brief Title
Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema
Acronym
REVEAL
Official Title
A Randomized, Double-masked, Multicenter, Laser Controlled Phase III Study Assessing the Efficacy and Safety of Ranibizumab (Intravitreal Injections) as Adjunctive and Monotherapy in Patients With Visual Impairment Due to Diabetic Macular Edema
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

5. Study Description

Brief Summary
This study was designed to confirm the efficacy and safety of ranibizumab (0.5 mg) as adjunctive therapy when added to laser photocoagulation and/or as monotherapy in Asian patients with visual impairment due to Diabetic Macular Edema (DME).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Macular Edema
Keywords
DME, Diabetic, macula, edema, ranibizumab, REVEAL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
396 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adjunctive treatment
Arm Type
Experimental
Arm Description
Adjunctive administration of ranibizumab 0.5 mg intravitreal injections and active laser.
Arm Title
Monotherapy treatment
Arm Type
Experimental
Arm Description
Monotherapy ranibizumab 0.5 mg intravitreal injections plus sham laser.
Arm Title
Laser control
Arm Type
Active Comparator
Arm Description
Active laser treatment plus sham intravitreal injections.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Intervention Description
Ranibizumab 0.5 mg intravitreal injection at day 1, month 1 and month 2. If stable vision not reached at month 3, one injection per month continued until stable vision was reached. Intravitreal injections re-initiated if needed.
Intervention Type
Procedure
Intervention Name(s)
Laser photocoagulation
Intervention Description
Active laser treatment administered at day 1. Subsequent laser treatments administered if needed at intervals no shorter than 3 months from previous laser treatment.
Intervention Type
Drug
Intervention Name(s)
Sham ranibizumab
Intervention Description
Sham intravitreal injections to ranibizumab at day 1, month 1 and month 2. Intravitreal injections re-initiated if needed.
Intervention Type
Procedure
Intervention Name(s)
Sham laser photocoagulation
Intervention Description
Sham laser treatment administered at day 1.
Primary Outcome Measure Information:
Title
Average Change From Baseline of Best-Corrected Visual Acuity (BCVA) Over 12 Months (From Month 1 to Month 12 Compared to Baseline)
Description
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change From Baseline on Central Retinal Subfield Thickness (CRST) at Month 12
Description
Central Retinal Subfield Thickness (CRST) was measured using Optical Coherence Tomography (OCT) in micrometers. A negative change from baseline of CRST indicates improvement.
Time Frame
12 months
Title
Percent of Participants With Anatomical Changes in Intra-retinal Cysts at End of Study Compared to Baseline
Description
Presence or absence of intra-retinal cysts in any of the 6 sections of the study eye was measured using Optical Coherence Tomography (OCT). A complete resolution or decrease from baseline of intra-retinal cysts indicates improvement.
Time Frame
Up to 12 months
Title
Percent of Participants With Anatomical Changes in Sub-retinal Fluid at End of Study Compared to Baseline
Description
Presence or absence of sub-retinal fluid in any of the 6 sections of the study eye was measured using Optical Coherence Tomography (OCT). A complete resolution or decrease from baseline of sub-retinal fluid indicates improvement.
Time Frame
Up to 12 months
Title
Percent of Participants With Visual Acuity Above 73 Letters at Month 12
Description
Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at month 12 indicates a positive outcome.
Time Frame
12 months
Title
Percent of Participants Who Gained >= 10 Letters at Month 12 Compared to Baseline
Description
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A gain of 10 or more BCVA letters from baseline indicates improvement. A BCVA of 84 letters or more at Month 12 indicates improvement.
Time Frame
12 months
Title
Percent of Participants Who Lost >= 10 Letters at Month 12 Compared to Baseline
Description
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A loss of 10 or more BCVA letters from baseline indicates worsening.
Time Frame
12 months
Title
Percent of Participants Who Gained >= 15 Letters at Month 12 Compared to Baseline
Description
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A gain of 15 or more BCVA letters from baseline indicates improvement. A BCVA of 84 letters or more at Month 12 indicates improvement.
Time Frame
12 months
Title
Percent of Participants Who Lost >= 15 Letters at Month 12 Compared to Baseline
Description
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A loss of 15 or more BCVA letters from baseline indicates worsening.
Time Frame
12 months
Title
Best-Corrected Visual Acuity (BCVA) Mean Change From Baseline at Month 12
Description
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.
Time Frame
12 months
Title
Patient Outcome Measure Euro Quality of Life Questionnaire (EQ-5D)
Description
The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Participants self-rate their health on a visual, vertical analogue scale from 0 to 100 where the endpoints are labeled "Best imaginable health state" (100) and "worst imaginable health state" (0).
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with Type 1 or Type 2 diabetes mellitus according to American Diabetes Association (ADA) or World Health Organization (WHO) guidelines with HbA1c not more than 10.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes. Patients with visual impairment due to focal or diffuse Diabetic Macular Edema in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected for study treatment unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for study treatment. The study eye must fulfill the following criteria at Visit 1: Best-Corrected Visual Acuity (BCVA) score between 78 and 39 letters, inclusively, using Early Treatment of Diabetic Retinopathy (ETDRS) chart-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160). Decrease in vision is due to DME and not due to other causes, in the opinion of the investigator. Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study. Exclusion Criteria: Ocular concomitant conditions/ diseases: Concomitant conditions in the study eye which could, in the opinion of the investigator, prevent the improvement of visual acuity on study treatment. Active intraocular inflammation in either eye. Any active infection in either eye. History of uveitis in either eye. Uncontrolled glaucoma in either eye. Ocular treatments: Panretinal laser photocoagulation in the study eye within 6 months prior to or during the study. Focal/grid laser photocoagulation in the study eye within 3 months prior to study entry. Systemic conditions or treatments: History of stroke Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine level > 2.0 mg/dL. Untreated diabetes mellitus Blood pressure systolic > 160 mmHg or diastolic > 100 mmHg Compliance/ Administrative: Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Beijing
Country
China
Facility Name
Novartis Investigative Site
City
Changsha
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
Country
China
Facility Name
Novartis Investigative Site
City
Guangzhou
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
Country
China
Facility Name
Novartis Investigational Site
City
Shanghai
Country
China
Facility Name
Novartis Investigative Site
City
Wenzhou
Country
China
Facility Name
Novartis Investigative Site
City
Xi'an
Country
China
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Chiba
Country
Japan
Facility Name
Novartis Investigative Site
City
Chiyoda-ku
Country
Japan
Facility Name
Novartis Investigative Site
City
Chuo-ku
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukushima
Country
Japan
Facility Name
Novartis Investigative Site
City
Hirakata
Country
Japan
Facility Name
Novartis Investigative Site
City
Kita-gun
Country
Japan
Facility Name
Novartis Investigative Site
City
Kobe
Country
Japan
Facility Name
Novartis Investigative Site
City
Kyoto
Country
Japan
Facility Name
Novartis Investigative Site
City
Mitaka
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagoya
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
Country
Japan
Facility Name
Novartis Investigative Site
City
Otsu
Country
Japan
Facility Name
Novartis Investigative Site
City
Shimotsuke
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita
Country
Japan
Facility Name
Novartis Investigative Site
City
Toyko
Country
Japan
Facility Name
Novartis Investigative Site
City
Urayasu
Country
Japan
Facility Name
Novartis Investigative Site
City
Wakayama
Country
Japan
Facility Name
Novartis Investigative Site
City
Yamagata
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
Country
Singapore
Facility Name
Novartis Investigative Site
City
Kaohsiung
Country
Taiwan
Facility Name
Novartis Investigative Site
City
LinKou
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema

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