Wet Macular DegenerationPhase 2NCT02571972
Dorzolamide-timolol Drops With Injections to Treat AMD, RVO or DME.
A Phase 2 study testing Dorzolamide-timolol in people with Wet Macular Degeneration and Age-related Macular Degeneration, run by Wills Eye at 1 site in United States.
Trial summary
This study seeks to evaluate the effect of topical aqueous suppression on the anatomic and functional response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in non-responders with wet age-related macular degeneration. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Wet Macular Degeneration, Age-related Macular Degeneration, Diabetic Macular Edema
- What is being tested?
- Dorzolamide-timolol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2015to 20 Dec 2015
- Phase
- Phase 2
- 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
- Patient of Wills Eye Hospital Retina Service and/or Mid Atlantic Retina.
- Volunteer patients age 18 years and older.
- Healthy enough to participate in the study.
- Willing and able to consent to participation in the study.
- Diagnosis of wet age-related macular degeneration
- 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
- Injection of the same anti-VEGF agent for at least two visits prior to study enrollment
- Fixed interval between at least two visits prior to study enrollment
Who cannot join
- History of uveitis
- Any ophthalmic surgery within previous 6 months, including cataract extraction.
- Any history of vitrectomy
- History of any glaucoma drop usage or prior glaucoma surgery
- Systemic diuretic or corticosteroid usage
- Any contraindication (bradycardia, decompensated heart failure, or reactive
Show all 9Show fewer
- airway disease) for topical use of a beta-blocker
- Any history of sulfonamide allergy
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Wills Eye Hospital / Mid Atlantic Retina
Philadelphia, Pennsylvania, 19107
About this study
Official title: Effect of Topical Aqueous Suppressants on Response to Intravitreal Anti-vascular Endothelial Growth Factor Injections in Age-related Macular Degeneration (AMD), Retinal Vein Occlusions (RVO) or Diabetic Macular Edema (DME).
This study seeks to evaluate the effect of topical aqueous suppression on the anatomic and functional response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in non-responders with wet age-related macular degeneration.
Read the detailed description
Intravitreal anti-vascular endothelial growth factor (VEGF) agents, including bevacizumab, ranibizumab, and aflibercept, have become the gold standard 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 philosophies. Despite frequent and consistent treatment with anti-VEGF therapy, there is a subset of patients who are incomplete or non-responders and have persistent evidence of exudation on spectral-domain optical coherence tomography (SD-OCT), including subretinal fluid (SRF) and/or intraretinal edema.
While clearance of intravitreal anti-VEGF drugs is not completely understood, some studies have suggested that outflow through the anterior chamber may contribute. We hypothesized that by decreasing aqueous production, outflow may also be reduced which could delay the clearance of intravitreal drugs. As a result, we chose topical dorzolamide-timolol since it is a potent aqueous suppressant and is readily available due to its common use in the treatment of glaucoma. The current study aimed to evaluate the efficacy of topical dorzolamide-timolol on anatomic and visual outcomes in anti-VEGF non-responders with neovascular AMD.
Significance: The results of this study will help delineate whether topical aqueous suppression may be useful as adjuvant therapy in patients receiving chronic intravitreal anti-VEGF injections.
- Conditions
- Wet Macular Degeneration, Age-related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion
- Being tested
- Dorzolamide-timolol
- Keywords
- dorzolamide-timolol, topical aqueous suppression, neovascular age-related macular degeneration, macular edema, intravitreal injection, anti-vascular endothelial growth factor
- Medical subject headings
- Wet Macular Degeneration, Macular Degeneration, Retinal Vein Occlusion, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dorzolamide-timololDrug
Also called Cosopt
On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
| Study group | Role | What they receive |
|---|---|---|
| Dorzolamide-timolol | Experimental | * On enrollment, eligible patients will have visual acuity testing, intraocular pressure, dilated fundoscopic examination, SD-OCT scan and will then receive the same intravitreal pharmacologic agent administered at prior visit.
* Subsequent follow-up visits will be at an identical interval to pre-enrollment visit intervals (4, 5, or 6 week intervals) for the study duration.
* Each subsequent visit will consist of visual acuity testing, intraocular pressure, dilated fundoscopic examination, SD-OCT scan, and intravitreal injection of same pharmacologic agent as prior visits
* At study conclusion, mean central macular thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height will be measured over the study period for all patients Receives: Drug: Dorzolamide-timolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Central Subfield Thickness (CST)
Mean central subfield thickness (CST) on spectral domain optical coherence tomography (SD-OCT) on 1 visit prior to enrollment and all visits subsequent to study enrollment
Measured: 3 visits (8-12 weeks)
Secondary outcomes (3)
Visual Acuity
LogMAR Visual acuity on enrollment and final visit
Measured: 3 visits (8-12 weeks)
Maximum Subretinal Fluid Height
Measurement based on SD-OCT
Measured: 3 visits (8-12 weeks)
Maximum Pigment Epithelial Detachment Height
Measurement based on SD-OCT
Measured: 3 visits (8-12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2015 (estimated)
- Study start1 Feb 2015
- Primary completion30 Sep 2015
- Study completion20 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Wet Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wills Eye
- Sponsor type
- University, hospital or other
- Collaborators
- J. Arch McNamara Research Fund, Mid Atlantic Retina
- Responsible party
- Principal investigator, Jason Hsu, MD, Wills Eye
- Investigators
- Jason Hsu, MD, Principal investigator, Wills Eye Hospital, Mid Atlantic Retina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02571972
- Sponsor's protocol ID
- IRB#14-435
- Status last verified
- Dec 2019
- First submitted
- 6 Oct 2015
- Last updated
- 3 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Byeon SH, Kwon OW, Song JH, Kim SE, Park YS. Prolongation of activity of single intravitreal bevacizumab by adjuvant topical aqueous depressant (Timolol-Dorzolamide). Graefes Arch Clin Exp Ophthalmol. 2009 Jan;247(1):35-42. doi: 10.1007/s00417-008-0917-1. Epub 2008 Aug 6.
PubMed 18682969Sridhar 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 26914218Obeid A, Hsu J, Ehmann D, Gao X, Sridhar J, Chiang A, Park CH, Ho AC. TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY. Retin Cases Brief Rep. 2021 Mar 1;15(2):120-126. doi: 10.1097/ICB.0000000000000752.
PubMed 29864044
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Topical Aqueous Suppressants on Response to Intravitreal Anti-vascular Endothelial Growth Factor Injections in Age-related Macular Degeneration (AMD), Retinal Vein Occlusions (RVO) or Diabetic Macular Edema (DME).
- ClinicalTrials.gov ID
- NCT02571972
- Acronym / sponsor ID
- IRB#14-435
- Conditions
- Wet Macular Degeneration, Age-related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion
- Keywords
- dorzolamide-timolol, topical aqueous suppression, neovascular age-related macular degeneration, macular edema, intravitreal injection, anti-vascular endothelial growth factor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Wills EyeUniversity, hospital or other
- Collaborators
- J. Arch McNamara Research Fund, Mid Atlantic Retina
- Study start
- 1 Feb 2015 (actual)
- Primary completion
- 30 Sep 2015 (actual)
- Study completion
- 20 Dec 2015 (actual)
- First posted
- 8 Oct 2015 (estimated)
- Results
- Posted 3 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study seeks to evaluate the effect of topical aqueous suppression on the anatomic and functional response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in non-responders with wet age-related macular degeneration.
Detailed description
Intravitreal anti-vascular endothelial growth factor (VEGF) agents, including bevacizumab, ranibizumab, and aflibercept, have become the gold standard 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 philosophies. Despite frequent and consistent treatment with anti-VEGF therapy, there is a subset of patients who are incomplete or non-responders and have persistent evidence of exudation on spectral-domain optical coherence tomography (SD-OCT), including subretinal fluid (SRF) and/or intraretinal edema.
While clearance of intravitreal anti-VEGF drugs is not completely understood, some studies have suggested that outflow through the anterior chamber may contribute. We hypothesized that by decreasing aqueous production, outflow may also be reduced which could delay the clearance of intravitreal drugs. As a result, we chose topical dorzolamide-timolol since it is a potent aqueous suppressant and is readily available due to its common use in the treatment of glaucoma. The current study aimed to evaluate the efficacy of topical dorzolamide-timolol on anatomic and visual outcomes in anti-VEGF non-responders with neovascular AMD.
Significance: The results of this study will help delineate whether topical aqueous suppression may be useful as adjuvant therapy in patients receiving chronic intravitreal anti-VEGF injections.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dorzolamide-timolol | Experimental | Drug: Dorzolamide-timolol* On enrollment, eligible patients will have visual acuity testing, intraocular pressure, dilated fundoscopic examination, SD-OCT scan and will then receive the same intravitreal pharmacologic agent administered at prior visit. * Subsequent follow-up visits will be at an identical interval to pre-enrollment visit intervals (4, 5, or 6 week intervals) for the study duration. * Each subsequent visit will consist of visual acuity testing, intraocular pressure, dilated fundoscopic examination, SD-OCT scan, and intravitreal injection of same pharmacologic agent as prior visits * At study conclusion, mean central macular thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height will be measured over the study period for all patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient of Wills Eye Hospital Retina Service and/or Mid Atlantic Retina.
- Volunteer patients age 18 years and older.
- Healthy enough to participate in the study.
- Willing and able to consent to participation in the study.
- Diagnosis of wet age-related macular degeneration
Key exclusion criteria (9 listed)
- History of uveitis
- Any ophthalmic surgery within previous 6 months, including cataract extraction.
- Any history of vitrectomy
- History of any glaucoma drop usage or prior glaucoma surgery
- Systemic diuretic or corticosteroid usage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dorzolamide-timololAlso: CosoptOn enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration | Drug | Dorzolamide-timolol |
Primary outcome
Mean Central Subfield Thickness (CST)
Time frame: 3 visits (8-12 weeks)
Mean central subfield thickness (CST) on spectral domain optical coherence tomography (SD-OCT) on 1 visit prior to enrollment and all visits subsequent to study enrollment
3 secondary outcomes
Visual Acuity
Time frame: 3 visits (8-12 weeks)
Maximum Subretinal Fluid Height
Time frame: 3 visits (8-12 weeks)
Maximum Pigment Epithelial Detachment Height
Time frame: 3 visits (8-12 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18682969Byeon SH, Kwon OW, Song JH, Kim SE, Park YS. Prolongation of activity of single intravitreal bevacizumab by adjuvant topical aqueous depressant (Timolol-Dorzolamide). Graefes Arch Clin Exp Ophthalmol. 2009 Jan;247(1):35-42. doi: 10.1007/s00417-008-0917-1. Epub 2008 Aug 6.
- Results publication: PubMed 26914218Sridhar 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.
- Derived from this study: PubMed 29864044Obeid A, Hsu J, Ehmann D, Gao X, Sridhar J, Chiang A, Park CH, Ho AC. TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY. Retin Cases Brief Rep. 2021 Mar 1;15(2):120-126. doi: 10.1097/ICB.0000000000000752.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Hsu, MD principal investigator
Wills Eye Hospital, Mid Atlantic Retina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dorzolamide-timolol in people with Wet Macular Degeneration and Age-related Macular Degeneration, run by Wills Eye at 1 site 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 9 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 3 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Dec 2019). 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?
Mean Central Subfield Thickness (CST) (time frame: 3 visits (8-12 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 NCT02571972, which also lists 3 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 3 Dec 2019.