Diabetic Macular EdemaPhase 3REVEALNCT00989989
Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema
A Phase 3 study testing Ranibizumab and Laser photocoagulation in people with Diabetic Macular Edema, run by Novartis at 35 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Ranibizumab and Laser photocoagulation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 396 participants
- Where
- 35 sitesin 6 countries
- Study dates
- Sep 2009to Aug 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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
Trial locations and contacts
35 sites in 6 countries.
35 sites in 6 countries
Japan20 sites
Novartis Investigative Site
Chiba
Novartis Investigative Site
Chiyoda-ku
Novartis Investigative Site
Chūōku
Novartis Investigative Site
Fukuoka
Novartis Investigative Site
Fukushima
Novartis Investigative Site
Hirakata
Novartis Investigative Site
Kita-gun
Novartis Investigative Site
Kobe
Novartis Investigative Site
Kyoto
Novartis Investigative Site
Mitaka
Novartis Investigative Site
Nagoya
Novartis Investigative Site
Osaka
Novartis Investigative Site
Ōtsu
Novartis Investigative Site
Shimotsuke
Novartis Investigative Site
Shinjuku-ku
Novartis Investigative Site
Suita
Novartis Investigative Site
Toyko
Novartis Investigative Site
Urayasu
Novartis Investigative Site
Wakayama
Novartis Investigative Site
Yamagata
China9 sites
Novartis Investigative Site
Beijing
Novartis Investigative Site
Changsha
Novartis Investigative Site
Chengdu
Novartis Investigative Site
Chongqing
Novartis Investigative Site
Guangzhou
Novartis Investigative Site
Hangzhou
Novartis Investigational Site
Shanghai
Novartis Investigative Site
Wenzhou
Novartis Investigative Site
Xi'an
Taiwan3 sites
Novartis Investigative Site
Kaohsiung City
Novartis Investigative Site
Linkou District
Novartis Investigative Site
Taipei
About this study
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
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).
- Conditions
- Diabetic Macular Edema
- Being tested
- Ranibizumab, Laser photocoagulation, Sham ranibizumab, Sham laser photocoagulation
- Keywords
- DME, Diabetic, macula, edema, ranibizumab, REVEAL
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
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.
Laser photocoagulationProcedure or surgery
Active laser treatment administered at day 1. Subsequent laser treatments administered if needed at intervals no shorter than 3 months from previous laser treatment.
Sham ranibizumabDrug
Sham intravitreal injections to ranibizumab at day 1, month 1 and month 2. Intravitreal injections re-initiated if needed.
Sham laser photocoagulationProcedure or surgery
Sham laser treatment administered at day 1.
| Study group | Role | What they receive |
|---|---|---|
| Adjunctive treatment | Experimental | Adjunctive administration of ranibizumab 0.5 mg intravitreal injections and active laser. Receives: Drug: Ranibizumab; Procedure: Laser photocoagulation |
| Monotherapy treatment | Experimental | Monotherapy ranibizumab 0.5 mg intravitreal injections plus sham laser. Receives: Drug: Ranibizumab; Procedure: Sham laser photocoagulation |
| Laser control | Active comparator | Active laser treatment plus sham intravitreal injections. Receives: Procedure: Laser photocoagulation; Drug: Sham ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (10)
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.
Measured: 12 months
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.
Measured: Up to 12 months
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.
Measured: Up to 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 396 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00989989
- Sponsor's protocol ID
- CRFB002D2303
- Acronym
- REVEAL
- Status last verified
- Sep 2012
- First submitted
- 2 Oct 2009
- Last updated
- 18 Oct 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00989989
- Acronym / sponsor ID
- REVEAL / CRFB002D2303
- Conditions
- Diabetic Macular Edema
- Keywords
- DME, Diabetic, macula, edema, ranibizumab, REVEAL
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 396 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 6 Oct 2009 (estimated)
- Results
- Posted 18 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Adjunctive treatment | Experimental | Drug: Ranibizumab, Procedure: Laser photocoagulationAdjunctive administration of ranibizumab 0.5 mg intravitreal injections and active laser. |
| Monotherapy treatment | Experimental | Drug: Ranibizumab, Procedure: Sham laser photocoagulationMonotherapy ranibizumab 0.5 mg intravitreal injections plus sham laser. |
| Laser control | Active comparator | Procedure: Laser photocoagulation, Drug: Sham ranibizumabActive laser treatment plus sham intravitreal injections. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (17 listed)
- Ocular concomitant conditions/ diseases:
- Ocular treatments:
- Systemic conditions or treatments:
- Compliance/ Administrative:
- Other protocol-defined inclusion/exclusion criteria may apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanibizumabRanibizumab 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. | Drug | Adjunctive treatment, Monotherapy treatment |
| Laser photocoagulationActive laser treatment administered at day 1. Subsequent laser treatments administered if needed at intervals no shorter than 3 months from previous laser treatment. | Procedure or surgery | Adjunctive treatment, Laser control |
| Sham ranibizumabSham intravitreal injections to ranibizumab at day 1, month 1 and month 2. Intravitreal injections re-initiated if needed. | Drug | Laser control |
| Sham laser photocoagulationSham laser treatment administered at day 1. | Procedure or surgery | Monotherapy treatment |
Primary outcome
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
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.
10 secondary outcomes
Change From Baseline on Central Retinal Subfield Thickness (CRST) at Month 12
Time frame: 12 months
Percent of Participants With Anatomical Changes in Intra-retinal Cysts at End of Study Compared to Baseline
Time frame: Up to 12 months
Percent of Participants With Anatomical Changes in Sub-retinal Fluid at End of Study Compared to Baseline
Time frame: Up to 12 months
Percent of Participants With Visual Acuity Above 73 Letters at Month 12
Time frame: 12 months
Percent of Participants Who Gained >= 10 Letters at Month 12 Compared to Baseline
Time frame: 12 months
Percent of Participants Who Lost >= 10 Letters at Month 12 Compared to Baseline
Time frame: 12 months
Percent of Participants Who Gained >= 15 Letters at Month 12 Compared to Baseline
Time frame: 12 months
Percent of Participants Who Lost >= 15 Letters at Month 12 Compared to Baseline
Time frame: 12 months
Best-Corrected Visual Acuity (BCVA) Mean Change From Baseline at Month 12
Time frame: 12 months
Patient Outcome Measure Euro Quality of Life Questionnaire (EQ-5D)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Diabetic Macular Edema
Active, not recruitingObservational study
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Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
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A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
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COMO: A Phase 3 Randomized, Double-Masked Study Comparing the Efficacy of EYP-1901 Against Aflibercept in DME
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis
35 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ranibizumab and Laser photocoagulation in people with Diabetic Macular Edema, run by Novartis at 35 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Japan, China, Taiwan, Hong Kong, Singapore and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2012.