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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00989989
First received: October 2, 2009
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

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).


Condition Intervention Phase
Diabetic Macular Edema
Drug: Ranibizumab
Procedure: Laser photocoagulation
Drug: Sham ranibizumab
Procedure: Sham laser photocoagulation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

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) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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).


Enrollment: 396
Study Start Date: September 2009
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjunctive treatment
Adjunctive administration of ranibizumab 0.5 mg intravitreal injections and active laser.
Drug: Ranibizumab
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.
Procedure: Laser photocoagulation
Active laser treatment administered at day 1. Subsequent laser treatments administered if needed at intervals no shorter than 3 months from previous laser treatment.
Experimental: Monotherapy treatment
Monotherapy ranibizumab 0.5 mg intravitreal injections plus sham laser.
Drug: Ranibizumab
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.
Procedure: Sham laser photocoagulation
Sham laser treatment administered at day 1.
Active Comparator: Laser control
Active laser treatment plus sham intravitreal injections.
Procedure: Laser photocoagulation
Active laser treatment administered at day 1. Subsequent laser treatments administered if needed at intervals no shorter than 3 months from previous laser treatment.
Drug: Sham ranibizumab
Sham intravitreal injections to ranibizumab at day 1, month 1 and month 2. Intravitreal injections re-initiated if needed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989989

Locations
China
Novartis Investigative Site
Beijing, China
Novartis Investigative Site
Changsha, China
Novartis Investigative Site
Chengdu, China
Novartis Investigative Site
Chongqing, China
Novartis Investigative Site
Guangzhou, China
Novartis Investigative Site
Hangzhou, China
Novartis Investigational Site
Shanghai, China
Novartis Investigative Site
Wenzhou, China
Novartis Investigative Site
Xi'an, China
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Japan
Novartis Investigative Site
Chiba, Japan
Novartis Investigative Site
Chiyoda-ku, Japan
Novartis Investigative Site
Chuo-ku, Japan
Novartis Investigative Site
Fukuoka, Japan
Novartis Investigative Site
Fukushima, Japan
Novartis Investigative Site
Hirakata, Japan
Novartis Investigative Site
Kita-gun, Japan
Novartis Investigative Site
Kobe, Japan
Novartis Investigative Site
Kyoto, Japan
Novartis Investigative Site
Mitaka, Japan
Novartis Investigative Site
Nagoya, Japan
Novartis Investigative Site
Osaka, Japan
Novartis Investigative Site
Otsu, Japan
Novartis Investigative Site
Shimotsuke, Japan
Novartis Investigative Site
Shinjuku-ku, Japan
Novartis Investigative Site
Suita, Japan
Novartis Investigative Site
Toyko, Japan
Novartis Investigative Site
Urayasu, Japan
Novartis Investigative Site
Wakayama, Japan
Novartis Investigative Site
Yamagata, Japan
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Republic of
Singapore
Novartis Investigative Site
Singapore, Singapore
Taiwan
Novartis Investigative Site
Kaohsiung, Taiwan
Novartis Investigative Site
LinKou, Taiwan
Novartis Investigative Site
Taipei, Taiwan
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00989989     History of Changes
Other Study ID Numbers: CRFB002D2303
Study First Received: October 2, 2009
Results First Received: July 26, 2012
Last Updated: September 18, 2012
Health Authority: China: Ministry of Health
China: Food and Drug Administration
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Japan: Foundation for Biomedical Research and Innovation
Japan: Institutional Review Board
Japan: Ministry of Education, Culture, Sports, Science and Technology
Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency
Hong Kong: Department of Health
Taiwan: Department of Health
Korea: Food and Drug Administration

Keywords provided by Novartis:
DME
Diabetic
macula
edema
ranibizumab
REVEAL

Additional relevant MeSH terms:
Macular Edema
Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on September 18, 2014