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Neovascular Age-related Macular DegenerationPhase 2/3DAWNNCT03034772

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

A Phase 2/3 study testing Dorzolamide-timolol and Artificial tears in people with Neovascular Age-related Macular Degeneration and Wet Macular Degeneration, run by Wills Eye at 5 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

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. Read more about this study

Who is it for?
Ages 45 years and older
What is being tested?
Dorzolamide-timolol and Artificial tears
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
5 sitesUnited States
Study dates
8 Feb 2017to 5 Jul 2019
Phase
Phase 2/3
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 45 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Active choroidal neovascularization (CNV) due to AMD.
  • 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.
  • Baseline CST ≥ 270 µm on SD-OCT automated retinal thickness map.
  • Injection of the same anti-VEGF agent at each of the two visits immediately preceding study enrollment.
  • Time interval of 5 weeks (± 1 week) between visits for at least two visits immediately preceding study enrollment.
  • Subjects of either gender aged ≥ 45 years.
  • Provide written informed consent
  • Ability to comply with study and follow-up procedures and return for study visits.

Who cannot join

  • History of uveitis.
  • 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.
  • Any ophthalmic surgery within previous 6 months, including cataract extraction.
  • Any history of vitrectomy or glaucoma surgery (e.g., trabeculectomy, tube shunt).
  • Current prescription eye drop usage (e.g., glaucoma drops, corticosteroid drops, etc.).
  • Any contraindication for topical use of a beta-blocker (e.g., bradycardia, decompensated heart failure, chronic obstructive pulmonary disease, reactive airway disease, asthma, etc.).
  • Any history of sulfonamide allergy.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Ophthalmic Consultants of Boston

    Boston, Massachusetts, 02114

  • Retina Consultants of Houston

    Houston, Texas, 77030

  • Palo Alto Medical Foundation

    Palo Alto, California, 94301

  • Mid Atlantic Retina- Wills Eye Institute

    Philadelphia, Pennsylvania, 19107

  • Associated Retinal Consultants

    Royal Oak, Michigan, 48073

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Dorzolamide-timolol, Artificial tears
Keywords
neovascular, wet, age-related, macular degeneration, dorzolamide, timolol
Medical subject headings
Wet Macular Degeneration, Macular Degeneration

What participants receive

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

  • Dorzolamide-timololDrug

    Also called Cosopt

    Topical eye drop (active comparator) used twice daily for study duration

  • Artificial tearsOther

    Topical eye drop (placebo comparator) used twice daily for study duration

Study groups in NCT03034772
Study groupRoleWhat they receive
Dorzolamide-timololActive comparatorTopical dorzolamide-timolol twice daily for the study duration. All patients will continue to receive intravitreal anti-VEGF injections at regularly scheduled intervals.
Receives: Drug: Dorzolamide-timolol
Artificial tearsPlacebo comparatorTopical artificial tears twice daily for the study duration. All patients will continue to receive intravitreal anti-VEGF injections at regularly scheduled intervals.
Receives: Other: Artificial tears

What is being measured

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

  1. Change in Mean Central Subfield Thickness (CST)

    Change in mean CST on spectral domain optical coherence tomography from baseline to the final visit

    Measured: Baseline and 18 weeks

Secondary outcomes (4)

  1. Change in Mean Maximum Subretinal Fluid (SRF) Height

    Change in mean maximum SRF height on spectral domain optical coherence tomography from baseline to final visit.

    Measured: Baseline and 18 weeks

  2. Change in Mean Maximum Pigment Epithelial Detachment (PED) Height

    Change in mean maximum PED height on spectral domain optical coherence tomography from baseline to final visit.

    Measured: Baseline and 18 weeks

  3. Change in Visual Acuity

    Change in mean best available visual acuity from baseline to final visit.

    Measured: Baseline and 18 weeks

  4. Change in Mean Intraocular Pressure (IOP)

    Change in mean IOP from baseline to final visit.

    Measured: Baseline and 18 weeks

Timeline

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

  1. First posted27 Jan 2017 (estimated)
  2. Study start8 Feb 2017
  3. Primary completion8 Feb 2019
  4. Study completion5 Jul 2019

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03034772
Sponsor's protocol ID
16-596
Acronym
DAWN
Status last verified
Jun 2020
First submitted
25 Jan 2017
Last updated
19 Jun 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sridhar J, Hsu J, Shahlaee A, Garg SJ, Spirn MJ, Fineman MS, Vander J. Topical Dorzolamide-Timolol With Intravitreous Anti-Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2016 Apr;134(4):437-43. doi: 10.1001/jamaophthalmol.2016.0045.

    PubMed 26914218

  • Hsu J, Patel SN, Wolfe JD, Shah CP, Chen E, Jenkins TL, Wibbelsman TD, Obeid A, Mikhail M, Garg SJ, Ho AC, Chiang A, Spirn MJ, Vander JF. Effect of Adjuvant Topical Dorzolamide-Timolol vs Placebo in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmol. 2020 May 1;138(5):560-567. doi: 10.1001/jamaophthalmol.2020.0724.

    PubMed 32239190

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Dorzolamide-timolol and Artificial tears in people with Neovascular Age-related Macular Degeneration and Wet Macular Degeneration, run by Wills Eye at 5 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 8 inclusion and 7 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 19 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 19 Jun 2020). 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?

Change in Mean Central Subfield Thickness (CST) (time frame: Baseline and 18 weeks). 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 NCT03034772, 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 19 Jun 2020.

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