Combination of Ranibizumab and Targeted Laser Photocoagulation

NCT ID: NCT04444492

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-25
• Study Completion Date: 2027-11-30

Brief Summary

Intravitreal injections of Ranibizumab will be applied in all patients according to treatment guidelines. The experimental group will receive additional targeted laser photocoagulation of the peripheral areas of capillary non-perfusion (up to 4 laser treatments within 1st year of the study). Based on the long-term observation after CoRaLa I study an importantly shorter duration of treatment and a relevant reduction of the total number of re-injections in RL patients is expected.

Detailed Description

Retinal vein occlusion (RVO) is the second most common retinal vascular disease leading to visual impairment. Main cause for visual impairment in CRVO (Central Retinal Vein Occlusion) is macular edema (ME) while neovascularization of the retina and/or the anterior segment is the most serious complication leading to vitreous hemorrhage, retinal detachment and neovascular glaucoma. In serious cases loss of vision is imminent. To date, no causal treatment has been proven to be effective in large trials. Intravitreal injections of drugs that inhibit the vascular endothelial growth factor (VEGF) and other inflammatory factors are the current treatments of choice for ME due to CRVO. Two different anti-VEGF drugs (ranibizumab and aflibercept), and a biodegradable dexamethasone implant are approved by the EMA (European Medicines Agency). Based on data from confirmatory studies anti-VEGF-drugs are recommended as a treatment of first choice in patients with RVO. All intravitreal drugs provide only a temporary effect with need for re-treatment for recurrences of ME. Mean number of ranibizumab application needed in CRVO patients was found to be 7.4 to 10.2 injections in 12 months. A significant number of CRVO patients require treatment over several years. Need for repetitive treatments and ophthalmic controls are a major burden for patients (and their relatives who are required for driving the patients to ophthalmologists) despite of only few adverse events and generally well-tolerated injections. Endophthalmitis is the most severe ocular complication which can be eye-sight-threatening. The more injections are administered, the higher is the cumulative risk of complications. Due to high costs (>1000 € per injection) treatment with repeated injections over years is of significant socio-economic importance, too. Therefore, treatments concepts which would lead to permanent reduction of ME and/or significantly reduce the number of re-injections over long-term periods are the major currently unmet need in patients with RVO.

Until now, several studies evaluated the impact of the additional pan-retinal laser photocoagulation in patients undergoing the anti-VEGF-treatment for the ME due to retinal vein occlusions. However, most of the studies are limited by retrospective design, small number of evaluated patients or lack of the randomization. None of the available prospective randomized studies had sufficient power to finally clarify the benefit of the additional laser treatment. Therefore, there is an unmet need for a large randomized, prospective, multicentric trials.

The proposed study will be the first sufficiently powered trial evaluating the long-term effect of targeted laser photocoagulation performed selectively (targeted) in peripheral areas of non-perfusion in combination with standard anti-VEGF treatment (ranibizumab injections) on the duration of the required intravitreal treatment over time period of 2 years.

Conditions

Central Retinal Vein Occlusion With Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ranibizumab+Laser-arm

Ranibizumab injections and additional targeted laser

Group Type: EXPERIMENTAL

Ranibizumab Injection

Intervention Type: DRUG

initial three injections of Ranibizumab - afterwards pro re nata monthly

Laser photocoagulation

Intervention Type: DEVICE

Areas of capillary non-perfusion will be treated with photocoagulation upto 4 times

Ranibizumab-arm

Only Ranibizumab injections

Group Type: ACTIVE_COMPARATOR

Ranibizumab Injection

Intervention Type: DRUG

initial three injections of Ranibizumab - afterwards pro re nata monthly

Interventions

Ranibizumab Injection

initial three injections of Ranibizumab - afterwards pro re nata monthly

Intervention Type: DRUG

Laser photocoagulation

Areas of capillary non-perfusion will be treated with photocoagulation upto 4 times

Intervention Type: DEVICE

Other Intervention Names

Lucentis

Eligibility Criteria

Inclusion Criteria

• Diagnosis of macular edema due to central retinal vein occlusion foveal thickness > 250 μm (measured by OCT)
• Age > 18 years
• Written informed consent of the patient
• BCVA score in the study eye between 24 letters (20/320) and 78 letters (20/25) measured in ETDRS chart
• History of CRVO no longer than 6 months
• Presence of capillary non-perfusion in peripheral retina larger than 5 disc areas documented in ultra wide-field fluorescein angiography
• Ability and willingness to attend all scheduled visits and assessments

Exclusion Criteria

• CRVO with ischemic maculopathy defined as diameter of the foveolar avascular zone larger than 2 optic disc diameters
• Macular edema due to another etiology than retinal vein occlusion (e.g. diabetic maculopathy, uveitis, age related macular degeneration, Irvine-Gass syndrome)
• History of idiopathic central serous chorioretinopathy
• Presence of vitreoretinal interface disease (e.g. vitreomacular traction, epiretinal membrane), either on clinical examination or in OCT
• An eye that, in the investigator's opinion, would not benefit from resolution of macular edema, such as eyes with foveal atrophy, dense pigmentary changes, or dense subfoveal hard exudates
• Aphakia in the study eye
• Scatter laser photocoagulation or macular photocoagulation in the study eye prior to study entry
• Intraocular or periocular injection of steroids in the study eye prior to study entry
• Previous use of an anti-VEGF drug in the study eye
• Cataract surgery or any other intraocular surgery in the study eye within 3 months prior to study entry
• Uncontrolled glaucoma (defined as intraocular pressure ≥ 30 mm Hg despite treatment with maximal anti-glaucoma medications)
• History of stroke, myocardial infarction, transient ischemic attacks within 3 months prior to the study
• Pregnancy (positive urine pregnancy test) or lactation
• The presence of active malignancy, including lymphoproliferative disorders.
• History of allergy to fluorescein or any component of the ranibizumab formulation
• Active intraocular infection
• Participation in another simultaneous interventional medical investigation or trial
• Women with child bearing potency without effective contraception (i. e. implants, injectables, combined oral contraceptives, some IUDs or vasectomised partner) during the conduct of the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leipzig

OTHER

Sponsor Role: collaborator

University of Giessen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matus Rehak, Professor

Role: STUDY_DIRECTOR

Department of Ophthalmology Justus-Liebig-Universität Giessen

Locations

Medizinische Universität Innsbruck, Klinik für Augenheilkunde und Optometrie

Innsbruck, , Austria

Site Status: NOT_YET_RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden Klinik und Polyklinik für Augenheilkunde

Dresden, , Germany

Site Status: WITHDRAWN

Internationale Innovative Ophthalmochirurgie GbR, Klinik für Augenchirurgie

Düsseldorf, , Germany

Site Status: WITHDRAWN

Universitätsklinikum Klinik für Augenheilkunde Freiburg

Freiburg im Breisgau, , Germany

Site Status: RECRUITING

Universitätsklinikum Gießen, Klinik und Poliklinik für Augenheilkunde

Giessen, , Germany

Site Status: RECRUITING

Hannover MHH Universitätsklinik für Augenheilkunde

Hanover, , Germany

Site Status: RECRUITING

University Hospital of Leipzig Department of Ophthalmology

Leipzig, , Germany

Site Status: RECRUITING

Klinikum der Stadt Ludwigshafen Augenklinik

Ludwigshafen, , Germany

Site Status: RECRUITING

Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg Klinik für Augenheilkunde

Marburg, , Germany

Site Status: RECRUITING

Ludwig-Maximilians-Universität München, Augenklinik

München, , Germany

Site Status: RECRUITING

Augenzentrum am St. Franziskus-Hospital Münster

Münster, , Germany

Site Status: RECRUITING

Universitätsklinikum Klinik für Augenheilkunde

Münster, , Germany

Site Status: WITHDRAWN

Universitätsklinikum Tübingen, Department für Augenheilkunde

Tübingen, , Germany

Site Status: RECRUITING

Universitätsklinikum Ulm, Klinik für Augenheilkunde

Ulm, , Germany

Site Status: RECRUITING

Augen-OP-Zentrum Zschopau, Praxis für Augenheilkunde

Zschopau, , Germany

Site Status: ACTIVE_NOT_RECRUITING

Countries

Austria; Germany

Central Contacts

Matus Rehak, Professor

Role: CONTACT

matus.rehak@uk-gm.de

0049 641 985 438 01

Yasmine Breitenstein

Role: CONTACT

yasmine.breitenstein@zks.uni-leipzig.de

0049 341 97 16 247

Facility Contacts

Matus Rehak, Prof. MUDr.

Role: primary

Hansjürgen Agostini, Prof.

Role: primary

Lyubomyr Lytvynchuk, MD

Role: primary

Amelie Pielen, PD. Dr.

Role: primary

Focke Ziemssen, Prof. Dr.

Role: primary

Lars-Olof Hattenbach, Prof.

Role: primary

Walter Sekundo, Prof.

Role: primary

Siegfried Prieglinger, Prof. Dr.

Role: primary

Georg Spital, Dr.

Role: primary

Alexandra Schweig, Dr.

Role: primary

Armin Hilmar Wolf, Prof. Dr.

Role: primary

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

CoRaLaII

Identifier Type: -

Identifier Source: org_study_id