Dorzolamide-timolol in Combination With Anti-vascular Endothelial Growth Factor Injections for Wet Age-related Macular Degeneration (DAWN)

June 5, 2020 updated by: Jason Hsu, MD, Wills Eye

A Randomized Controlled Trial Comparing the Effect of Topical Dorzolamide-Timolol Versus Placebo Combined With Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) Injections in Patients With Neovascular Age-Related Macular Degeneration Who Are Incomplete Anti-VEGF Responders

A previous pilot study demonstrated that commonly available glaucoma drops (dorzolamide-timolol) might decrease the amount of chronic swelling in patient with wet age-related macular degeneration who have been receiving anti-vascular endothelial growth factor (VEGF) injections. This will be a larger study where subjects are randomly assigned to receive the glaucoma drops or a placebo (artificial tears) in order to confirm whether this previous finding is valid. Subjects will continue to receive the normally scheduled anti-VEGF injections at regular intervals as done prior to enrollment. The only addition to the regimen will be the daily use of eye drops (dorzolamide-timolol or artificial tears) twice daily for the duration of the study. At the end of the study, the swelling in the retina will be compared to the amount before starting the drops to see if there is any difference between the group using dorzolamide-timolol versus artificial tears.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intravitreal anti-vascular endothelial growth factor (VEGF) agents, including ranibizumab and aflibercept, remain the standard of care treatment for neovascular age-related macular degeneration (AMD). Various treatment modalities using these agents have been proposed, including monthly, pro re nata, and treat-and-extend regimens. Despite frequent and consistent treatment with anti-VEGF therapy, there is a subset of patients who are incomplete responders and have persistent exudation, including intraretinal edema, subretinal fluid (SRF), and/or retinal pigment epithelial detachment (PED) on spectral-domain optical coherence tomography (SD-OCT). While clearance of intravitreal anti-VEGF drugs is not completely understood, some studies have suggested that outflow through the anterior chamber may play a role. We hypothesized that by decreasing aqueous production, outflow may also be reduced which could subsequently slow the clearance of intravitreal drugs. In a prior pilot study with 10 eyes of 10 patients who were incomplete responders with neovascular AMD, the effect of topical dorzolamide-timolol in combination with continued intravitreal anti-VEGF injections was explored. Patients were kept on the same anti-VEGF drug as well as the same interval between injections for the 2 visits before enrollment and through the course of the pilot study in order to minimize the chances that any changes noted might be the result of altering one of these variables. The mean central subfield thickness (CST) decreased from 419.7 μm at enrollment to 334.1 μm at the final visit (p=0.012). Mean maximum subretinal fluid (SRF) height decreased from 126.6 μm at enrollment to 56.5 μm at the final visit (p=0.020). This decrease in mean CST and SRF was significant beginning at the first visit after initiation of the drops. Based on this initial pilot data, dorzolamide-timolol appears to be a promising adjuvant treatment in combination with anti-VEGF injections for incomplete anti-VEGF responders with neovascular AMD. However, since there was no control group in the pilot study, it is possible that the decreased exudation seen was a result of the continued anti-VEGF therapy alone rather than an effect of the topical therapy. As a result, a randomized, placebo-controlled clinical trial will be better able to assess the efficacy of dorzolamide-timolol in this setting.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94301
        • Palo Alto Medical Foundation
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Ophthalmic Consultants of Boston
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • Associated Retinal Consultants
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Mid Atlantic Retina- Wills Eye Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Retina Consultants of Houston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Active choroidal neovascularization (CNV) due to AMD.
  2. Prior treatment with at least 4 injections of anti-VEGF agents in the past 6 months and persistent intraretinal and/or subretinal fluid on SD-OCT at each visit during this period.
  3. Baseline CST ≥ 270 µm on SD-OCT automated retinal thickness map.
  4. Injection of the same anti-VEGF agent at each of the two visits immediately preceding study enrollment.
  5. Time interval of 5 weeks (± 1 week) between visits for at least two visits immediately preceding study enrollment.
  6. Subjects of either gender aged ≥ 45 years.
  7. Provide written informed consent
  8. Ability to comply with study and follow-up procedures and return for study visits.

Exclusion Criteria:

  1. History of uveitis.
  2. Presence of intraocular inflammation, significant epiretinal membrane (causing distortion of macular anatomy per investigator discretion), significant vitreomacular traction (per investigator discretion), macular hole, or vitreous hemorrhage.
  3. Any ophthalmic surgery within previous 6 months, including cataract extraction.
  4. Any history of vitrectomy or glaucoma surgery (e.g., trabeculectomy, tube shunt).
  5. Current prescription eye drop usage (e.g., glaucoma drops, corticosteroid drops, etc.).
  6. Any contraindication for topical use of a beta-blocker (e.g., bradycardia, decompensated heart failure, chronic obstructive pulmonary disease, reactive airway disease, asthma, etc.).
  7. Any history of sulfonamide allergy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Dorzolamide-timolol
Topical dorzolamide-timolol twice daily for the study duration. All patients will continue to receive intravitreal anti-VEGF injections at regularly scheduled intervals.
Drug: Dorzolamide-timolol
Topical eye drop (active comparator) used twice daily for study duration
Other Names:
  • Cosopt
PLACEBO_COMPARATOR: Artificial tears
Topical artificial tears twice daily for the study duration. All patients will continue to receive intravitreal anti-VEGF injections at regularly scheduled intervals.
Other: Artificial tears
Topical eye drop (placebo comparator) used twice daily for study duration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean Central Subfield Thickness (CST)
Time Frame: Baseline and 18 weeks
Change in mean CST on spectral domain optical coherence tomography from baseline to the final visit
Baseline and 18 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean Maximum Subretinal Fluid (SRF) Height
Time Frame: Baseline and 18 weeks
Change in mean maximum SRF height on spectral domain optical coherence tomography from baseline to final visit.
Baseline and 18 weeks
Change in Mean Maximum Pigment Epithelial Detachment (PED) Height
Time Frame: Baseline and 18 weeks
Change in mean maximum PED height on spectral domain optical coherence tomography from baseline to final visit.
Baseline and 18 weeks
Change in Visual Acuity
Time Frame: Baseline and 18 weeks
Change in mean best available visual acuity from baseline to final visit.
Baseline and 18 weeks
Change in Mean Intraocular Pressure (IOP)
Time Frame: Baseline and 18 weeks
Change in mean IOP from baseline to final visit.
Baseline and 18 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wills Eye

Collaborators

Mid Atlantic Retina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 8, 2017

Primary Completion (ACTUAL)

February 8, 2019

Study Completion (ACTUAL)

July 5, 2019

Study Registration Dates

First Submitted

January 25, 2017

First Submitted That Met QC Criteria

January 26, 2017

First Posted (ESTIMATE)

January 27, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 19, 2020

Last Update Submitted That Met QC Criteria

June 5, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-596

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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