Ischemic Central Retinal Vein OcclusionPhase 1NCT00406471
Rubeosis Anti-VEGF (RAVE) Trial for Ischemic Central Retinal Vein Occlusion
A Phase 1 study testing Ranibizumab (Lucentis) in people with Ischemic Central Retinal Vein Occlusion, run by Greater Houston Retina Research at 1 site in United States.
Trial summary
The RAVE (Rubeosis Anit-VEgf) trial, utilizes monthly intravitreal Ranibizumab (Lucentis) injections for 9 months to see if total VEGF blockade will prevent neovascular glaucoma and eliminate the need for panretinal photocoagulation in patients with ischemic central retinal vein occlusion. Read more about this study
- Who is it for?
- Ages 19 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ischemic Central Retinal Vein Occlusion
- What is being tested?
- Ranibizumab (Lucentis)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Jan 2011
- Phase
- Phase 1
- 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 19 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age > 18 years
- Ischemic CRVO within 3 months of enrollment as per the following inclusion criteria
- Three of the following clinical tests must be present to demonstrate ischemic CRVO:
- VA 20/200 or worse
- RAPD 0.9 LU or worse
- Loss of 1-2e isopter on Goldmann Visual field (Kwon et al. 2001)
- ERG demonstrating b wave amplitude less than 60% of A wave
Who cannot join
- Angle neovascularization greater than 3 clock hours with IOP over 30 (Neovascular glaucoma)
- Any previous retinal laser photocoagulation to the study eye
- Any previous intravitreal injection in study eye (triamcinolone or other)
- Any previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
- Intracapsular cataract extraction (posterior capsule needs to be present)
- Previous history of retinal detachment in study eye
Show all 36Show fewer
- Any previous radiation treatments to head/ neck
- Inability to assess iris neovascularization (corneal opacity precluding gonioscopy)
- Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study
- Significant diabetic retinopathy in the fellow eye (diabetic macular edema, proliferative diabetic retinopathy, or high-risk non-proliferative diabetic retinopathy)
- Pregnancy (positive pregnancy test)
- Prior enrollment in any study for vein occlusion in the study eye
- Participation in another simultaneous medical investigator or trial
- Ocular disorders in the study eye that may confound interpretation of study results, including retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME AMD, ocular histoplasmosis, or pathologic myopia)
- Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period
- Aphakia or absence of the posterior capsule in the study eye
- Previous violation of the posterior capsule is also excluded unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
- History of idiopathic or autoimmune uveitis in either eye
- Structural damage to the center of the macula in the study eye preexisting to CRVO likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s)
- Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT
- Ocular inflammation (including trace or above) in the study eye
- Uncontrolled glaucoma (defined as intraocular pressure ≥30 mm Hg despite treatment with anti- medications) or previous filtration surgery in the study eye
- Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection
- Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, pre-operative spherical equivalent refractive error of more than -8 diopters myopia is not allowed) Systemic Conditions
- Uncontrolled Blood pressure exceeding diastolic pressure of 100 mm Hg (sitting) during the screening period
- Uncontrolled diabetes mellitus
- Renal failure requiring dialysis or renal transplant
- Premenopausal women not using adequate contraception
- Previous participation in other studies of investigational drugs (excluding vitamins and minerals) within 3 months preceding Day 0
- History of other disease, metabolic dysfunction, physical examination finding, or other findings giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications
- INR ≥ 3.0 (e.g. due to current treatment with warfarin). The use of aspirin is not an exclusion.
- Other
- History of allergy to fluorescein, not amenable to treatment
- Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
- Inability to comply with study or follow up procedures
- History of allergy to humanized antibodies or any component of the ranibizumab formulation
Trial locations and contacts
1 site in 1 country.
About this study
The RAVE (Rubeosis Anit-VEgf) trial, utilizes monthly intravitreal Ranibizumab (Lucentis) injections for 9 months to see if total VEGF blockade will prevent neovascular glaucoma and eliminate the need for panretinal photocoagulation in patients with ischemic central retinal vein occlusion.
Read the detailed description
The most devastating complication of ischemic CRVO is the development of anterior segment neovascularization and the resulting morbidity from neovascular glaucoma. This complication appears to be directly correlated with intraocular VEGF levels. Currently there is no proven treatment to decrease the formation of rubeosis. Current management of the disease consists of pan-retinal photocoagulation once significant anterior segment neovascularization becomes manifest. This treatment destroys peripheral retina (with peripheral retinal field) and presumably works by eventually lowering ocular VEGF levels which causes secondary regression of rubeosis.
As ranibizumab blocks VEGF, this treatment when delivered intraocularly may prevent neo-vascular glaucoma while preserving peripheral visual fields in this patient population.
Risks of intravitreal injections are well known and include endophthalmitis and retinal detachment. This risk should be less than 1% with proper injection technique and experienced retinal surgeons. As the incidence of neovascular glaucoma (with resultant loss of central and peripheral visual fields) is approximately 50% in ischemic CRVO, the small risk of intravitreal injection is warranted if the drug shows efficacy. In a small number of subjects in previous animal and human trials, intraocular pressure was acutely elevated when the drug volume was placed intravitreally. An eye with a compromised circulation (such as ischemic CRVO) may experience less perfusion if this occurred. Previous intravitreal studies of ranibizumab have not utilized anterior chamber paracentesis to compensate for the volume of intravitreal drug to be placed. This was reasonable because an eye with a normal retinal circulation can tolerate relatively high intraocular pressure for a limited time. This protocol for this study will include anterior chamber paracentesis prior to intravitreal injection to minimize this potential risk.
- Conditions
- Ischemic Central Retinal Vein Occlusion
- Being tested
- Ranibizumab (Lucentis)
- Keywords
- Ischemic, Central, Retinal, Vein, Occlusion, Ranibizumab, Lucentis, CRVO, ISCRVO
- Medical subject headings
- Ischemia, Bites and Stings
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ranibizumab (Lucentis)Drug
500 microgram intravitreal injection for 8 months or 300 microgram intravitreal injection for 8 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 500 micrograms of ranibizumab Receives: Drug: Ranibizumab (Lucentis) |
| 2 | Active comparator | 300 microgram ranibizumab Receives: Drug: Ranibizumab (Lucentis) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preservation of 5Ve isopter Goldmann visual field versus baseline at 1 year
Measured: 12 and 24 months
Estimate the % of subjects progressing to neovascular glaucoma requiring pan-retinal photocoagulation or glaucoma surgery after treatment with ranibizumab (comparing 0.3mg to 0.5mg doses)
Measured: 12 and 24 mponths
Secondary outcomes (10)
Assess the systemic and local safety of 0.3mg and 0.5mg of ranibizumab in patients with ischemic CRVO
Measured: 12 and 24 months
Assess improvement from baseline in Visual Acuity at 1 year
Measured: 12 and 24 months
Assess the impact on retinal thickness and volume (as measured by OCT)
Measured: 12 and 24 months
Assess the impact of ranibizumab (0.3mg and 0.5mg) on time to improvement in visual acuity
Measured: 12 and 24 months
Asses the impact of ranibizumab (0.3mg and 0.5mg) on time to improvement in retinal thickness
Measured: 12 and 24 months
Asses the impact of ranibizumab (0.3mg and 0.5mg) on percentage of patients developing 3 or more clock hours of rubeosis at 6 and 12 months and 24 months
Measured: 6, 12, and 24 months
Assess the impact of ranibizumab (0.3mg and 0.5mg) on prevention of greater than 3 clock hours rubeosis (as measured by iris fluorescein angiography)
Measured: 12 and 24 months
Assess the impact of ranibizumab on the gain or decrease of area of visual field on 14e Goldman visual field area
Measured: 12 and 24 months
Assess the impact of ranibizumab on b wave component of ERG
Measured: 12 and 24 months
Aqueous VEGF levels
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2006 (estimated)
- Study startMay 2005
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic Central Retinal Vein OcclusionStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Greater Houston Retina Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David M. Brown, M.D., Greater Houston Retina Research
- Investigators
- David M Brown, MD, Principal investigator, Vitreoretinal Consultants
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00406471
- Sponsor's protocol ID
- RAVE
- Other IDs
- NCT00406471
- Status last verified
- Mar 2013
- First submitted
- 30 Nov 2006
- Last updated
- 14 Mar 2013
- Results posted
- No
Publications
Wykoff CC, Brown DM, Croft DE, Major JC Jr, Wong TP. Progressive retinal nonperfusion in ischemic central retinal vein occlusion. Retina. 2015 Jan;35(1):43-7. doi: 10.1097/IAE.0000000000000277.
PubMed 25102193Wykoff CC, Brown DM, Croft DE, Wong TP. Two Year SAVE Outcomes: 2.0 mg ranibizumab for recalcitrant neovascular AMD. Ophthalmology. 2013 Sep;120(9):1945-6.e1. doi: 10.1016/j.ophtha.2013.06.030. No abstract available.
PubMed 24001533
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rubeosis Anti-VEGF (RAVE) Trial for Ischemic Central Retinal Vein Occlusion
- ClinicalTrials.gov ID
- NCT00406471
- Acronym / sponsor ID
- RAVE
- Conditions
- Ischemic Central Retinal Vein Occlusion
- Keywords
- Ischemic, Central, Retinal, Vein, Occlusion, Ranibizumab, Lucentis, CRVO
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Greater Houston Retina ResearchUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 4 Dec 2006 (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.
The RAVE (Rubeosis Anit-VEgf) trial, utilizes monthly intravitreal Ranibizumab (Lucentis) injections for 9 months to see if total VEGF blockade will prevent neovascular glaucoma and eliminate the need for panretinal photocoagulation in patients with ischemic central retinal vein occlusion.
Detailed description
The most devastating complication of ischemic CRVO is the development of anterior segment neovascularization and the resulting morbidity from neovascular glaucoma. This complication appears to be directly correlated with intraocular VEGF levels. Currently there is no proven treatment to decrease the formation of rubeosis. Current management of the disease consists of pan-retinal photocoagulation once significant anterior segment neovascularization becomes manifest. This treatment destroys peripheral retina (with peripheral retinal field) and presumably works by eventually lowering ocular VEGF levels which causes secondary regression of rubeosis.
As ranibizumab blocks VEGF, this treatment when delivered intraocularly may prevent neo-vascular glaucoma while preserving peripheral visual fields in this patient population.
Risks of intravitreal injections are well known and include endophthalmitis and retinal detachment. This risk should be less than 1% with proper injection technique and experienced retinal surgeons. As the incidence of neovascular glaucoma (with resultant loss of central and peripheral visual fields) is approximately 50% in ischemic CRVO, the small risk of intravitreal injection is warranted if the drug shows efficacy. In a small number of subjects in previous animal and human trials, intraocular pressure was acutely elevated when the drug volume was placed intravitreally. An eye with a compromised circulation (such as ischemic CRVO) may experience less perfusion if this occurred. Previous intravitreal studies of ranibizumab have not utilized anterior chamber paracentesis to compensate for the volume of intravitreal drug to be placed. This was reasonable because an eye with a normal retinal circulation can tolerate relatively high intraocular pressure for a limited time. This protocol for this study will include anterior chamber paracentesis prior to intravitreal injection to minimize this potential risk.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Ranibizumab (Lucentis)500 micrograms of ranibizumab |
| 2 | Active comparator | Drug: Ranibizumab (Lucentis)300 microgram ranibizumab |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age > 18 years
- Ischemic CRVO within 3 months of enrollment as per the following inclusion criteria
- Three of the following clinical tests must be present to demonstrate ischemic CRVO:
Key exclusion criteria (36 listed)
- Angle neovascularization greater than 3 clock hours with IOP over 30 (Neovascular glaucoma)
- Any previous retinal laser photocoagulation to the study eye
- Any previous intravitreal injection in study eye (triamcinolone or other)
- Any previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
- Intracapsular cataract extraction (posterior capsule needs to be present)
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 |
|---|---|---|
| Ranibizumab (Lucentis)500 microgram intravitreal injection for 8 months or 300 microgram intravitreal injection for 8 months | Drug | 1, 2 |
Primary outcome
Preservation of 5Ve isopter Goldmann visual field versus baseline at 1 year
Time frame: 12 and 24 months
Estimate the % of subjects progressing to neovascular glaucoma requiring pan-retinal photocoagulation or glaucoma surgery after treatment with ranibizumab (comparing 0.3mg to 0.5mg doses)
Time frame: 12 and 24 mponths
10 secondary outcomes
Assess the systemic and local safety of 0.3mg and 0.5mg of ranibizumab in patients with ischemic CRVO
Time frame: 12 and 24 months
Assess improvement from baseline in Visual Acuity at 1 year
Time frame: 12 and 24 months
Assess the impact on retinal thickness and volume (as measured by OCT)
Time frame: 12 and 24 months
Assess the impact of ranibizumab (0.3mg and 0.5mg) on time to improvement in visual acuity
Time frame: 12 and 24 months
Asses the impact of ranibizumab (0.3mg and 0.5mg) on time to improvement in retinal thickness
Time frame: 12 and 24 months
Asses the impact of ranibizumab (0.3mg and 0.5mg) on percentage of patients developing 3 or more clock hours of rubeosis at 6 and 12 months and 24 months
Time frame: 6, 12, and 24 months
Assess the impact of ranibizumab (0.3mg and 0.5mg) on prevention of greater than 3 clock hours rubeosis (as measured by iris fluorescein angiography)
Time frame: 12 and 24 months
Assess the impact of ranibizumab on the gain or decrease of area of visual field on 14e Goldman visual field area
Time frame: 12 and 24 months
Assess the impact of ranibizumab on b wave component of ERG
Time frame: 12 and 24 months
Aqueous VEGF levels
Time frame: 24 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 14 Mar 2013.
- Derived from this study: PubMed 25102193Wykoff CC, Brown DM, Croft DE, Major JC Jr, Wong TP. Progressive retinal nonperfusion in ischemic central retinal vein occlusion. Retina. 2015 Jan;35(1):43-7. doi: 10.1097/IAE.0000000000000277.
- Derived from this study: PubMed 24001533Wykoff CC, Brown DM, Croft DE, Wong TP. Two Year SAVE Outcomes: 2.0 mg ranibizumab for recalcitrant neovascular AMD. Ophthalmology. 2013 Sep;120(9):1945-6.e1. doi: 10.1016/j.ophtha.2013.06.030. No abstract available.
- Related InfoLink provided by the sponsor.
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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.
David M Brown, MD principal investigator
Vitreoretinal Consultants
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ranibizumab (Lucentis) in people with Ischemic Central Retinal Vein Occlusion, run by Greater Houston Retina Research at 1 site in United States.
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 8 inclusion and 36 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 14 Mar 2013. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Preservation of 5Ve isopter Goldmann visual field versus baseline at 1 year (time frame: 12 and 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00406471, which also lists 2 linked publications.
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 14 Mar 2013.