Diabetic RetinopathyPhase 3NCT00545870
Bevacizumab Versus Ranibizumab for Diabetic Retinopathy
A Phase 3 study testing bevacizumab and Ranibizumab in people with Diabetic Retinopathy and Diabetic Macular Edema, run by Ursula Schmidt-Erfurth, M.D. at 1 site in Austria.
Trial summary
Treatment of diabetic macular edema with perifoveal focal/grid laser coagulation was found to be effective saving the visual acuity only in 50% of patients and only 3-14% of treated patients had an improved visual acuity postoperatively. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Retinopathy, Diabetic Macular Edema, Proliferative Diabetic Retinopathy
- What is being tested?
- bevacizumab and Ranibizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteAustria
- Study dates
- Jun 2008to Apr 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Age ≥18 years
- Patients with type 1 or type 2 diabetes mellitus
- HbA1C between 6% and 9 %.
- Patients with persistent diabetic macular edema with center involvement following completed grid lasercoagulation in the study eye
- Patients with persistent active neovascularisations following completed panretinal lasercoagulation (at least 2000 spots) in the study eye
- Last perifoveolar laser treatment 3 months before study entry
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- Central macular thickness (macular edema) of at least 300 - 550 microns in the central subfield as measured by OCT
- Not eligible for any currently approved treatments or experimental protocols
- Best corrected visual acuity, using ETDRS charts, of 20/25 to 20/200 (Snellen equivalent) in the study eye
- Patients with decrease in vision in the study eye due to foveal thickening from diabetic macular edema and not to other causes, in the opinion of the investigator
Who cannot join
- A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure
- History of systemic corticosteroids within 3 months prior to randomization or topical, rectal or inhaled corticosteroids in current use more than 3 times per week
- Panretinal laser photocoagulation within the past 3 months or macular laser photocoagulation within the past 3 months in the study eye
- Previous treatment with intravitreal or sub-Tenon triamcinolone within the past 3 months in the study eye
- Previous participation in clinical trial involving anti-angiogenic drugs (pegabtanib sodium, ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.)
- History of submacular surgery or other surgical intervention for diabetic macular edema except grid lasercoagulation in the study eye
- Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)
Trial locations and contacts
1 site in 1 country.
Austria1 site
Department of Ophthalmology, Medical University of Vienna
Vienna, State of Vienna, 1090
About this study
Official title: A Randomized, Double-masked Study With Intraocular Bevacizumab Compared With Intravitreal Ranibizumab in Patients With Persistent Diabetic Macular Edema or Persistent Active Neovascularisation Following Lasercoagulation
Treatment of diabetic macular edema with perifoveal focal/grid laser coagulation was found to be effective saving the visual acuity only in 50% of patients and only 3-14% of treated patients had an improved visual acuity postoperatively. The decent results of lasercoagulation are associated with potential side effects, as focal scotomas, change of color discrimination and development of epiretinal gliosis. The frequency of perifoveal laser treatments is anatomically limited in case of diabetic macular edema: after application of about 350 coagulates there is no possibility to repeat the laser treatment perifoveolar without creating confluent lasercoagulates and causing significant scotomas. In case of persistence of edema in spite of complete perifoveal grid coagulation, no standard therapy exists. Some previous studies investigated the effect of steroids in patients with diabetic macular edema unresponsive to grid laser photocoagulation, but the benefit on the visual acuity was only temporary and the intravitreal application was associated with significant side effects as cataract progression (up to 50%) and ocular hypertension (up to 20%).
In the Diabetic Retinopathy Study the 4-years rate for severe vision loss in patients with high-risk retinopathy was 20.4 %. In cases of proliferative retinopathy, panretinal (scatter) photocoagulation can reduce the risk for development of high-risk retinopathy by 50% over 6 years. When panretinal lasercoagulation is initiated, about 2000 laser spots are equally distributed in all four quadrants. Since panretinal photocoagulation bares risks like loss of field of vision, central vision reduction and loss of colour vision, this treatment can not be continued unlimited.
Read more
In cases of persisting neovascularisations in spite of panretinal photocoagulation, no evidence based therapy exists. There is a high risk for intravitreal bleeding, rubeosis, secondary glaucoma with severe vision loss. When fibrovascular proliferation leads to retinal detachment, vitreo-retinal surgery might be indicated.
Now we know that vascular endothelial growth factor (VEGF) is the major angiogenic stimulus responsible for increase of vasopermeability, cellproliferation and angiogenesis in diabetic retinopathy (DRP). Several studies, evaluating VEGF levels in vitreous, have indicated a role for VEGF in diabetic macular edema: vitreous samples of patients with diabetic macular edema contain elevated VEGF concentration and VEGF injected in experimental studies results in breakdown of the blood-retina barrier.
There is increasing evidence for a therapeutic role of anti-VEGF drugs not only in age-related macular degeneration but also in other diseases as in diabetic macular edema. Intravitreal injections have become the most favored treatment procedure for administering anti-VEGF drugs.
The side effects and the decent results of laser treatment on the visual acuity in diabetic macular edema led to studies using anti-VEGF therapy. Unpublished study results on the aptamer pegaptanib (Macugen™) are promising. A study using the antibody fragment Ranibizumab (Lucentis™) in patiens with diabetic macula edema is in progress. Ranibizumab is now approved to be used as an intravitreal injection.
Currently there is one additional anti-VEGF drug already on the market: Bevacizumab (Avastin™), which has approved as intravenous infusion for the treatment of metastatic colo-rectal cancer. Previous studies have shown that systemic use of Bevacizumab (Avastin™) can obtain very promising results on patients with choroidal neovascularisation (CNV) by age-related macular degenetration. This drug, a monoclonal full-length antibody, designed to bind all isoforms of VEGF is a large molecule. But case reports in patients with CNV caused by age-related macular degeneration and with macular edema from central retinal vein occlusion indicate that intravitreally given Bevacizumab (Avastin™) is effective in diseases originating from the choroids and the retina, too. These findings imply a sufficient penetration of the retina by Bevacizumab (Avastin™).
Based on these new findings and the important role of VEGF in diabetic retinopathy, we propose a pilot study for treatment of persistent diabetic macular edema or persisting active neovascularistaions following lasercoagulation with intravitreally administered Bevacizumab (Avastin™) or Ranibizumab (Lucentis™).
- Being tested
- bevacizumab, Ranibizumab
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
intravitreal application
RanibizumabDrug
intravitreal application
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Bevacizumab treatment Receives: Drug: bevacizumab |
| B | Active comparator | Ranibizumab treatment Receives: Drug: Ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the change in macular edema and the absolute change in visual acuity. To investigate the change of neovascularisation.
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 posted17 Oct 2007 (estimated)
- Study startJun 2008
- Primary completionMar 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic RetinopathyStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ursula Schmidt-Erfurth, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ursula Schmidt-Erfurth, M.D., Medical University of Vienna
- Investigators
- Ursula Schmidt-Erfurth, MD, Principal investigator, Dep. of Ophthalmology, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00545870
- Sponsor's protocol ID
- 238/2006
- Status last verified
- Apr 2015
- First submitted
- 16 Oct 2007
- Last updated
- 15 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-masked Study With Intraocular Bevacizumab Compared With Intravitreal Ranibizumab in Patients With Persistent Diabetic Macular Edema or Persistent Active Neovascularisation Following Lasercoagulation
- ClinicalTrials.gov ID
- NCT00545870
- Acronym / sponsor ID
- 238/2006
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Ursula Schmidt-Erfurth, M.D.University, hospital or other
- Study start
- Jun 2008
- Primary completion
- Mar 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 17 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment of diabetic macular edema with perifoveal focal/grid laser coagulation was found to be effective saving the visual acuity only in 50% of patients and only 3-14% of treated patients had an improved visual acuity postoperatively. The decent results of lasercoagulation are associated with potential side effects, as focal scotomas, change of color discrimination and development of epiretinal gliosis. The frequency of perifoveal laser treatments is anatomically limited in case of diabetic macular edema: after application of about 350 coagulates there is no possibility to repeat the laser treatment perifoveolar without creating confluent lasercoagulates and causing significant scotomas. In case of persistence of edema in spite of complete perifoveal grid coagulation, no standard therapy exists. Some previous studies investigated the effect of steroids in patients with diabetic macular edema unresponsive to grid laser photocoagulation, but the benefit on the visual acuity was only temporary and the intravitreal application was associated with significant side effects as cataract progression (up to 50%) and ocular hypertension (up to 20%).
In the Diabetic Retinopathy Study the 4-years rate for severe vision loss in patients with high-risk retinopathy was 20.4 %. In cases of proliferative retinopathy, panretinal (scatter) photocoagulation can reduce the risk for development of high-risk retinopathy by 50% over 6 years. When panretinal lasercoagulation is initiated, about 2000 laser spots are equally distributed in all four quadrants. Since panretinal photocoagulation bares risks like loss of field of vision, central vision reduction and loss of colour vision, this treatment can not be continued unlimited.
In cases of persisting neovascularisations in spite of panretinal photocoagulation, no evidence based therapy exists. There is a high risk for intravitreal bleeding, rubeosis, secondary glaucoma with severe vision loss. When fibrovascular proliferation leads to retinal detachment, vitreo-retinal surgery might be indicated.
Now we know that vascular endothelial growth factor (VEGF) is the major angiogenic stimulus responsible for increase of vasopermeability, cellproliferation and angiogenesis in diabetic retinopathy (DRP). Several studies, evaluating VEGF levels in vitreous, have indicated a role for VEGF in diabetic macular edema: vitreous samples of patients with diabetic macular edema contain elevated VEGF concentration and VEGF injected in experimental studies results in breakdown of the blood-retina barrier.
There is increasing evidence for a therapeutic role of anti-VEGF drugs not only in age-related macular degeneration but also in other diseases as in diabetic macular edema. Intravitreal injections have become the most favored treatment procedure for administering anti-VEGF drugs.
The side effects and the decent results of laser treatment on the visual acuity in diabetic macular edema led to studies using anti-VEGF therapy. Unpublished study results on the aptamer pegaptanib (Macugen™) are promising. A study using the antibody fragment Ranibizumab (Lucentis™) in patiens with diabetic macula edema is in progress. Ranibizumab is now approved to be used as an intravitreal injection.
Currently there is one additional anti-VEGF drug already on the market: Bevacizumab (Avastin™), which has approved as intravenous infusion for the treatment of metastatic colo-rectal cancer. Previous studies have shown that systemic use of Bevacizumab (Avastin™) can obtain very promising results on patients with choroidal neovascularisation (CNV) by age-related macular degenetration. This drug, a monoclonal full-length antibody, designed to bind all isoforms of VEGF is a large molecule. But case reports in patients with CNV caused by age-related macular degeneration and with macular edema from central retinal vein occlusion indicate that intravitreally given Bevacizumab (Avastin™) is effective in diseases originating from the choroids and the retina, too. These findings imply a sufficient penetration of the retina by Bevacizumab (Avastin™).
Based on these new findings and the important role of VEGF in diabetic retinopathy, we propose a pilot study for treatment of persistent diabetic macular edema or persisting active neovascularistaions following lasercoagulation with intravitreally administered Bevacizumab (Avastin™) or Ranibizumab (Lucentis™).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: bevacizumabBevacizumab treatment |
| B | Active comparator | Drug: RanibizumabRanibizumab treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥18 years
- Patients with type 1 or type 2 diabetes mellitus
- HbA1C between 6% and 9 %.
- Patients with persistent diabetic macular edema with center involvement following completed grid lasercoagulation in the study eye
- Patients with persistent active neovascularisations following completed panretinal lasercoagulation (at least 2000 spots) in the study eye
Key exclusion criteria (7 listed)
- A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure
- History of systemic corticosteroids within 3 months prior to randomization or topical, rectal or inhaled corticosteroids in current use more than 3 times per week
- Panretinal laser photocoagulation within the past 3 months or macular laser photocoagulation within the past 3 months in the study eye
- Previous treatment with intravitreal or sub-Tenon triamcinolone within the past 3 months in the study eye
- Previous participation in clinical trial involving anti-angiogenic drugs (pegabtanib sodium, ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.)
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 |
|---|---|---|
| bevacizumabintravitreal application | Drug | A |
| Ranibizumabintravitreal application | Drug | B |
Primary outcome
To investigate the change in macular edema and the absolute change in visual acuity. To investigate the change of neovascularisation.
Time frame: 12 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2015.
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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.
Ursula Schmidt-Erfurth, MD principal investigator
Dep. of Ophthalmology, Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bevacizumab and Ranibizumab in people with Diabetic Retinopathy and Diabetic Macular Edema, run by Ursula Schmidt-Erfurth, M.D. at 1 site in Austria.
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 10 inclusion and 7 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 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To investigate the change in macular edema and the absolute change in visual acuity. To investigate the change of neovascularisation. (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 15 Apr 2015.