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Central Retinal, Hemi Retinal & Brach Retinal Vein OcclusionsPhase 4WAVENCT01710839

Widefield Angiography Guided Targeted-retinal Photocoagulation Combined With Anti VEgf Intravitreal Injections for the Treatment of Ischemic Central Retinal Vein Occlusion, Hemi Retinal Vein Occlusion, and Branch Retinal Vein Occlusion

A Phase 4 study testing 0.5mg Ranibizumab and Targeted Pan Retinal Photocoagulation in people with Central Retinal, Hemi Retinal & Brach Retinal Vein Occlusions, run by Charles C Wykoff, PhD, MD at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To see if Lucentis 0.5mg combined with Targeted Pan Retinal photocoagulation will decrease the total number of intravitreal injections in a year for ischemic central retinal vein occlusion, hemi-retinal vein occlusions and branch retinal vein occlusions compared to standard of care Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
0.5mg Ranibizumab and Targeted Pan Retinal Photocoagulation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
3 sitesUnited States
Study dates
Oct 2012to Oct 2015
Phase
Phase 4
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

  • Age > 18 years
  • Visual acuity between 20/25 and 20/800, ETDRS best corrected visual acuity
  • Ability to provide written informed consent and comply with study assessments for the full duration of the study
  • Patients previously treated with any ITV anti-VEGF:
  • With at least 2 consecutive monthly intravitreal injections of anti-VEGF medications with presence of persistent or recurrent macular edema in the past 4 months

Who cannot join

  • IOP over 30 mm Hg
  • Any previous retinal laser photocoagulation to the study eye
  • Previous intravitreal injection in the study eye of any corticosteroid treatment
  • Previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
  • Intracapsular cataract extraction
  • Any previous radiation treatments to head/neck that the principal or sub investigator feels is clinically relevant
Show all 24Show fewer
  • Inability to assess iris or angle 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)
  • Participation in another simultaneous medical investigator or trial
  • Ocular disorders or concurrent disease in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention, including history of retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME, AMD, ocular histoplasmosis, or pathologic myopia)
  • Structural damage to the center of the macula in the study eye prior to CRVO, HRVO and BRVO 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 clinically significant epiretinal membrane in the study eye evident biomicroscopically or by OCT (vitreomacular attachment OK)
  • 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, preoperative spherical equivalent refractive error of more than -8 diopters myopia is not allowed)
  • Uncontrolled Blood pressure: defined as systolic pressure > 180mmHg and/or diastolic pressure of >110 mm Hg (sitting) during the screening period
  • Uncontrolled diabetes mellitus
  • Renal failure requiring dialysis or renal transplant
  • Pregnancy (positive pregnancy test) or lactation
  • Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
  • 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
  • History of allergy to fluorescein, not amenable to treatment
  • Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed by the principal investigator (PI) and/or the sub-investigator.
  • History of allergy to humanized antibodies or any component of the ranibizumab formulation

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Retina Consultants of Houston/The Medical Center

    Houston, Texas, 77030

  • Retina Consultants of Houston

    Katy, Texas, 77494

  • Retina Consultants of Houston

    The Woodlands, Texas, 77384

Other trials in United States

About this study

Official title: A Phase IV Open Label Trial of the Safety, Tolerability and Efficacy of 0.5mg Ranibizumab Intravitreal Injections Combined With Wide Field Angiography Guided Panretinal Photocoagulation vs. 0.5mg Ranibizumab Intravitreal Injection Monotherapy in Subjects With Ischemic Central Retinal Vein Occlusion, Hemi Retinal Vein Occlusion, and Branch Retinal Vein Occlusion Who Incompletely Respond to at Least 2 Consecutive Intravitreal Injections in the Past 4 Months.

To see if Lucentis 0.5mg combined with Targeted Pan Retinal photocoagulation will decrease the total number of intravitreal injections in a year for ischemic central retinal vein occlusion, hemi-retinal vein occlusions and branch retinal vein occlusions compared to standard of care

Read the detailed description

The WAVE trial is a phase IV, open label, 12-month trial of intravitreal ranibizumab 0.5 mg in patients (n=30) with ischemic CRVO, HRVO and BRVO who have been previously treated with ranibizumab or any other anti-VEGF intravitreal injection therapy, who are incomplete responders to 2 or more consecutive intravitreal anti-VEGF injections in the past 4 months. Randomization is 1:4, 1=control, ranibizumab only, 4=treatment arm. In total, 6 subjects will be randomized to control and 24 randomized to treatment arm.

Cohort 1- 24 Subjects previously treated Patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Wide field angiography guided peripheral targeted-retinal photocoagulation (TRP), will be divided into 2 sessions if needed, one at the 2 weeks post injection visit and another later at M4/V7, if repeat wide field angiogram indicates areas not sufficiently treated in the first TRP session

Cohort 2- 6 Subjects, previously treated patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Being tested
0.5mg Ranibizumab, Targeted Pan Retinal Photocoagulation
Keywords
CRVO, BRVO, HRVO, Macular edema, vein occlusion
Medical subject headings
Macular Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 0.5mg RanibizumabDrug

    Also called Lucentis

    intravitreal injections

  • Targeted Pan Retinal PhotocoagulationProcedure or surgery

    Also called PRP, Pan Retinal Photocoagulation, TRP, Pan Laser

    Targeted Pan Retinal Photocoagulation based on wide field angiography

Study groups in NCT01710839
Study groupRoleWhat they receive
Targeted Pan Retinal laser combined with 0.5mg ranibizumabExperimentalCohort 1 (n=24), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses of 0.5 mg ranibizumab followed by PRN treatment with ranibizumab 0.5 mg; after receiving the first loading dose of ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) based on 200° wide field angiography with possibility of a second session of TRP at M4/M7, if non-perfusion persists based on angiogram.The 200°wide field angiography will indicate areas of peripheral ischemia which will be selectively treated, preserving areas of more perfused retina.
Receives: Drug: 0.5mg Ranibizumab; Procedure: Targeted Pan Retinal Photocoagulation
Ranibizumab 0.5mgActive comparatorCohort 2 (n=6), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses followed by PRN monthly treatment with ranibizumab 0.5 mg.
Receives: Drug: 0.5mg Ranibizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total Number of Intravitreal Injections Over a 12 Month Period

    Assess the number of intravitreal injections over 12 months.

    Measured: 12 months

  2. Visual Acuity

    Evaluate the mean change from baseline in ETDRS best-corrected visual acuity at 12 months. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning.

    Measured: 12 month period

Secondary outcomes (7)
  1. Retinal Ischemia

    Quantify change in area of perfused and ischemic retina.

    Measured: 12 month period

  2. Foveal Avascular Zone

    Assess change in foveal avascular zone area and largest diameter, measured during the early phase of the angiogram

    Measured: 12 months

  3. Adverse Events

    Incidence and severity of adverse events (ocular and non-ocular).

    Measured: 12 months

  4. Neovascularization of the Iris, Optic Nerve and Elsewhere

    Percent of patients that develop neovascularization of the iris, optic nerve and/or elsewhere.

    Measured: 12 months

  5. Central Foveal Outcome

    Mean change in Central Foveal Volume on High Resolution OCT.

    Measured: 12 months

  6. Aqueous VEGF Levels

    VEGF, other cytokines and ranibizumab levels in aqueous and serum samples at randomization and at the exit or early termination visit.

    Measured: 12 Months

  7. Visual Field

    Goldman Visual Field changes at 6 and 12 months from baseline. Goldmann perimetry is a method used to map a patient's field of vision (central and peripheral). Changes will be assessed by manual digital quantification of GVF plots.

    Measured: 6 and 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionOct 2015
  4. Study completionOct 2015

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01710839
Sponsor's protocol ID
12246
Acronym
WAVE
Status last verified
Aug 2017
First submitted
17 Oct 2012
Last updated
8 Sep 2017
Data monitoring committee
No

Publications

  • Armaly MF. Ocular pressure and visual fields. A ten-year follow-up study. Arch Ophthalmol. 1969 Jan;81(1):25-40. doi: 10.1001/archopht.1969.00990010027005. No abstract available.

    PubMed 5763217
  • Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, Martin JF, Hykin PG. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol. 2002 Dec;120(12):1644-50. doi: 10.1001/archopht.120.12.1644.

    PubMed 12470137
  • Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1124-1133.e1. doi: 10.1016/j.ophtha.2010.02.022. Epub 2010 Apr 9.

    PubMed 20381871
  • Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology. 2011 Oct;118(10):2041-9. doi: 10.1016/j.ophtha.2011.02.038. Epub 2011 Jun 29.

    PubMed 21715011
  • A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995 Oct;102(10):1434-44.

    PubMed 9097789
  • Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group. Arch Ophthalmol. 1997 Apr;115(4):486-91. doi: 10.1001/archopht.1997.01100150488006.

    PubMed 9109757
  • Christen WG, Glynn RJ, Manson JE, Ajani UA, Buring JE. A prospective study of cigarette smoking and risk of age-related macular degeneration in men. JAMA. 1996 Oct 9;276(14):1147-51.

    PubMed 8827967
  • Conn G, Bayne ML, Soderman DD, Kwok PW, Sullivan KA, Palisi TM, Hope DA, Thomas KA. Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2628-32. doi: 10.1073/pnas.87.7.2628.

    PubMed 2320579
  • Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ, Siegel NR, Leimgruber RM, Feder J. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989 Nov;84(5):1470-8. doi: 10.1172/JCI114322.

    PubMed 2478587
  • Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J. Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017-24.

    PubMed 2584205
  • de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992 Feb 21;255(5047):989-91. doi: 10.1126/science.1312256.

    PubMed 1312256
  • Hayreh SS, Klugman MR, Podhajsky P, Kolder HE. Electroretinography in central retinal vein occlusion. Correlation of electroretinographic changes with pupillary abnormalities. Graefes Arch Clin Exp Ophthalmol. 1989;227(6):549-61. doi: 10.1007/BF02169451.

    PubMed 2483144
  • Fan W, Fleming A, Hemert JV, Wykoff CC, Brown DM, Robertson G, Wang K, Falavarjani KG, Sadda SR, Ip M. RETINAL VASCULAR BED AREA IN EYES WITH RETINAL VEIN OCCLUSION ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY: WAVE Study. Retina. 2022 Oct 1;42(10):1883-1888. doi: 10.1097/IAE.0000000000003549.

    PubMed 35976232
  • Wykoff CC, Ou WC, Wang R, Brown DM, Cone C, Zamora D, Le RT, Sagong M, Wang K, Sadda SR; WAVE Study Group. Peripheral Laser for Recalcitrant Macular Edema Owing to Retinal Vein Occlusion: The WAVE Trial. Ophthalmology. 2017 Jun;124(6):919-921. doi: 10.1016/j.ophtha.2017.01.049. Epub 2017 Mar 18. No abstract available.

    PubMed 28318636

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 0.5mg Ranibizumab and Targeted Pan Retinal Photocoagulation in people with Central Retinal, Hemi Retinal & Brach Retinal Vein Occlusions, run by Charles C Wykoff, PhD, MD at 3 sites 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 5 inclusion and 24 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 8 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 11 Apr 2017). 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?

Total Number of Intravitreal Injections Over a 12 Month Period (time frame: 12 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 NCT01710839, which also lists 14 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 8 Sep 2017.

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