To Compare Anti-VEGF Monotherapy With Anti-VEGF and EPM Grid Laser Combination Therapy for Diabetic Macular Edema (END-DME)

To Compare the Efficacy of Monotherapy With Anti-Vascular Endothelial Growth Factor (Ranibizumab or Bevacizumab) Versus Combination Therapy With Anti-Vascular Endothelial Growth Factor and End-point-management Grid Laser Photocoagulation for Diabetic Macular Edema

Objectives:

To compare the efficacy of monotherapy with anti-Vascular Endothelial Growth Factor (ranibizumab or bevacizumab) with combined therapy with anti-Vascular Endothelial Growth Factor and end-point-management grid laser photocoagulation for diabetic macular edema.

Study design:

Open-label non-randomized interventional study.

Study overview:

This study aims to look at the efficacy of treating diabetic macular edema (DME) with either anti-Vascular Endothelial Growth Factor(anti-VEGF) monotherapy, compared with combination therapy with anti-VEGF and End-Point-Management (EPM) grid laser photocoagulation, over a period of 6 months.

Various sites from across Asia (Japan, South Korea, Hong Kong) will participate. Depending on the availability of EPM laser, sites can either contribute to the 'Anti-VEGF monotherapy' arm, or to the 'Combination therapy' arm.

Study Overview

• Status: Unknown
• Conditions: Diabetic Macula Edema
• Intervention / Treatment: Drug: ranibizumab; Drug: Bevacizumab; Procedure: End-Point-Management grid laser

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • The University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years with CSME
• Diagnosis of diabetes mellitus (type 1 or type 2)
• At least one eye meets the study eye criteria
• Able and willing to provide informed consent prior to any study-related procedures
• Central foveal thickness ≥ 300 microns at baseline (SPECTRALIS or Cirrus HD OCT)
• LogMAR Best corrected visual acuity 0.20 (Snellen 20/30) to 1.3 (Snellen 20/400).
• Willing and able to comply with clinic visits and study-related procedures
• Central Foveal Thickness on OCT 300-600 micron
• After first injection, wait for ME to reduce before proceeding with the laser. Exclude if ME persists >500um at the 4-week follow up

Exclusion Criteria:

• Macular edema is considered to be due to a cause other than diabetic macular edema.
• An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, VMT, pigment epithelium abnormalities, dense subfoveal hard exudates, non-retinal condition such as glaucoma etc).
• Substantial cataract that, in the opinion of the investigator, is likely to be affecting visual acuity. Likely to be affecting BCVA and performing laser treatment.
• History of treatment for diabetic macular edema at any time in the past (such as grid macular photocoagulation).
• History of treatment for diabetic macular edema at any time in the past 3 months (such as intravitreal or peribulbar corticosteroids, ranibizumab, bevacizumab, aflibercept).
• Focal laser photocoagulation should be performed before enrolling into the study if needed. 3 months gap required between last laser procedure and recruitment.
• History of panretinal (scatter) photocoagulation (PRP) within 3 months prior to enrollment.
• Anticipated need for PRP in the study period.
• History of major retinal surgery (including vitrectomy, scleral buckle, any glaucoma surgery, etc.).
• History of YAG capsulotomy performed within 3 months.
• Aphakia.
• Intraocular pressure ≥ 25 mmHg.
• History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: history of angle-closure glaucoma is not an exclusion criterion).
• Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant Blepharitis.
• Systemic Exclusion Criteria: A subject is not eligible if any of the following exclusion criteria are present:
• Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
• A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
• Blood pressure > 180/110 (systolic above 180 OR diastolic above 110).
• Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
• Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization.
• Systemic anti-vascular growth factor (ranibizumab) or pro-VEGF treatment within 4 months.
• For women of childbearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
• Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the study.
• The target eye is the only eye of the subject, with the fellow eye's visual acuity lower than 1.3 LogMAR units.
• Baseline logMAR BCVA from 0.05 to 0.5 (Snellen)
• Fellow eye BCVA 0.05 or worse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Anti-VEGF and EPM laser; Subjects will receive both anti-VEGF injections and EPM laser.	Drug: ranibizumab; Drug: Bevacizumab; Procedure: End-Point-Management grid laser
Active Comparator: Anti-VEGF monotherapy; Subjects will receive anti-VEGF injections monotherapy.	Drug: ranibizumab; Drug: Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in number of anti-VEGF required	The number of injections of anti-VEGF required at the end of the 6 months period.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in best corrected visual acuity	The change in best corrected visual acuity among subjects in different groups at the end of the 6 months period when compared to baseline.	6 months
Central retinal thickness	The change in central retinal thickness among subjects in different groups at the end of the 6 months period when compared to baseline.	6 months
Treatment related complications	This will look at treatment related complications in terms of changes in intraocular pressure post-injection	6 months
Treatment related complications	This will look at treatment related complications in terms of infection	6 months
Treatment related complications	This will look at treatment related complications in terms of retinal detachment	6 months
Recurrence of macular edema	Recurrence of macular edema during the 6 months period will be monitored.	6 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: National University Hospital, Singapore; Korea University; Kyungpook National University Hospital; Inje University; Yeungnam University Hospital; Kyorin University; Nagoya City University; Chungnam National University Hospital; Kyoto University; Pusan National University; Asahikawa Medical College; Kyushu University; University of Fukui; Eguchi Eye Clinic; Nagasaki University; Osaka Medical College; Tokyo Medical University Hachioji Medical Centre; Hokkaido University; Sun Cheon Hyang University; Kyunghee University; Yamagata University
• Investigators: Principal Investigator: Ian Wong, FRCOphth, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: April 17, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: bevacizumab; ranibizumab; Diabetic Macula Edema; End-Point-Management
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Bevacizumab
• Other Study ID Numbers: END-DME1