Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema (REVEAL)
This study has been completed.
Sponsor:
Novartis
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00989989
First received: October 2, 2009
Last updated: September 18, 2012
Last verified: September 2012
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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:
Genetics Home Reference related topics:
age-related macular degeneration
X-linked juvenile retinoschisis
MedlinePlus related topics:
Edema
Drug Information available for:
Ranibizumab
U.S. FDA Resources
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
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:
|
Edema Macular Edema Vision, Low Vision Disorders Signs and Symptoms Macular Degeneration |
Retinal Degeneration Retinal Diseases Eye Diseases Sensation Disorders Neurologic Manifestations Nervous System Diseases |
ClinicalTrials.gov processed this record on May 23, 2013