Diabetic Macular EdemaDMENCT04856397
Ozurdex in Suboptimal Diabetic Macular Edema Patients
A study testing Intravitreal Implant in Applicator and Eylea in people with Diabetic Macular Edema, run by Uptown Eye Specialists.
Trial summary
The primary focus of this study is to understand the anatomic and visual outcomes of patients with refractory and suboptimal treatment response diabetic macular edema (DME) using anti-vascular endothelial growth factor (VEGF) to Ozurdex, an intravitreal dexamethasone implant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Intravitreal Implant in Applicator and Eylea
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- No sites listed yet
- Study dates
- 25 May 2021to 29 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Treatment-native patients with DME secondary to type I or type II diabetes mellitus
- Patients who require intravitreal anti-VEGF treatment
- Able to understand English and complete a pain assessment
- Suboptimal DME responders in patients who have received 3 or 6 eylea injections (non-cytokine group)
Who cannot join
- Deafness or communication disorder, known Dementia, Severe COPD/Asthma (severe lung disorder), Severe OSA, Psychiatric or Anxiety conditions, involuntary movement disorders, allergy to the anesthesia, any conditions requiring intraoperative iris manipulation, any prior ocular surgery; all patients who may need translation, are illiterate, or unable to provide consent.
- Pre-existing ocular pathology confounding outcome (i.e. uveitis, retinal vascular disease, macular degeneration etc.)
- Pre-existing uncontrolled glaucoma/high IOP
- Patients under 18
About this study
Official title: Ozurdex in Suboptimal Diabetic Macular Edema
The primary focus of this study is to understand the anatomic and visual outcomes of patients with refractory and suboptimal treatment response diabetic macular edema (DME) using anti-vascular endothelial growth factor (VEGF) to Ozurdex, an intravitreal dexamethasone implant. Secondly, investigators aim to understand the differences in cytokine profiles in patients who respond differently to intravitreal anti-VEGF versus Ozurdex. The importance of this study is to identify biomarkers that may help predict patients' response to different treatment protocols. Currently, Ozurdex is not covered by provincial health benefit plans for patients with DME. Our results may help improve access to care for those who have suboptimal results with or refractory to intravitreal anti-VEGF treatment.
Read the detailed description
Diabetic macular edema (DME) is the most common cause of vision loss in young patients with diabetes. Its pathophysiology starts with decreased retinal oxygen tension that manifests as retinal capillary hyperpermeability and increased intravascular pressure mediated by vascular endothelial growth factor (VEGF) upregulation and retinal vascular autoregulation, respectively. Spectral domain optical coherence tomography (SD-OCT) is the cornerstone of clinical assessment of DME. The foundation of treatment is metabolic control of hyperglycemia and blood pressure. Specific ophthalmic treatments of DME include intravitreal anti-VEGF drug injections, in the form of intravitreal Bevacizumab (Avastin), Ranibizumab (Lucentis), and Aflibercept (Eylea). Intravitreal corticosteroid injections, focal laser photocoagulation, and vitrectomy are other treatment options. A substantial fraction of eyes respond incompletely to all of these modalities resulting in visual loss and disordered retinal structure and vasculature visible on SD-OCT and OCT angiography. There is currently no consensus on when to switch from one treatment to another in the context of a suboptimal response. Our hypothesis is that patients who are switched early to Ozurdex and achieve an OCT proven dry state, achieve better functional outcomes than those patients who are switched late or not at all, by limiting exposure of the retina to potentially damaging inflammatory markers, and the merits associated with less frequent injections.
Suboptimal DME is defined as a central subfoveal retinal thickness of > 300 and the presence of intra or sub-retinal fluid with a minimum BCVA of 20/25 or worse after 3 injections of intravitreal aflibercept, from here on referred to as Eylea. Furthermore, there is some evidence that a subset of patients with refractory DME respond well to intravitreal corticosteroids, specifically, Ozurdex, which is a biodegradable, sustained-release intravitreal dexamethasone implant, designed to be potentially injected between 2-6 months. This medication is currently not covered by the Ontario health benefits plan for patients with DME and comes at a significant cost to patients.
Moreover, recent studies have confirmed the important role of inflammatory ocular cytokines in patients' response to intravitreal treatments in DME, much the same as neovascular age-related macular degeneration. However, it is not known which ocular cytokines determine the degree of response to various treatment modalities for DME.
Here, investigators aim to study the anatomic and visual outcomes, as well as the cytokine profile of patients with suboptimal DME in response to early vs. late switch to intravitreal Ozurdex treatment.
- Conditions
- Diabetic Macular Edema
- Being tested
- Intravitreal Implant in Applicator, Eylea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal Implant in ApplicatorDrug
Also called Ozurdex
Dexamethasone intravitreal implant
EyleaDrug
anti-VEGF medication
| Study group | Role | What they receive |
|---|---|---|
| Control group | Other | Responders will be in this category. These patients will be maintained on intravitreal anti-VEGF therapy for 1 year, with a monthly PRN ("as needed") treatment regimen post 5 monthly loading doses. Receives: Drug: Eylea |
| Early switch | Experimental | Suboptimal responders who are switched to intravitreal Ozurdex (monitored monthly and treated PRN at a potential 2-6 month interval) injections after the first 3 monthly loading intravitreal eylea. Receives: Drug: Intravitreal Implant in Applicator; Drug: Eylea |
| Late switch | Experimental | Suboptimal responders who are switched to intravitreal Ozurdex (monitored monthly and treated PRN at a potential 2-6 month interval) injections after the first 6 monthly loading intravitreal eylea Receives: Drug: Intravitreal Implant in Applicator; Drug: Eylea |
| Non-switch | Other | Suboptimal responders who continue to receive monthly intravitreal anti-VEGF injections. Receives: Drug: Eylea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual acuity
best corrected visual acuity (BCVA)
Measured: 1 year
Secondary outcomes (5)
OCT findings
Track anatomic outcomes on optical coherence tomography (OCT)
Measured: 1 year
OCTa findings
Track anatomic outcomes on optical coherence tomography angiography (OCTA)
Measured: 1 year
Cytokine expression TNFa
baseline cytokine profile of the aqueous humour of all patients prior to first dose of anti-VEGF. Cytokine TNFa
Measured: 1 year
Cytokine expression IL-8
baseline cytokine profile of the aqueous humour of all patients prior to first dose of anti-VEGF. Cytokine IL-8
Measured: 1 year
Cytokine expression IL-6
baseline cytokine profile of the aqueous humour of all patients prior to first dose of anti-VEGF. Cytokine IL-6
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2021
- Study start25 May 2021 (estimated)
- Primary completion30 Aug 2021 (estimated)
- Study completion29 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Macular EdemaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- There are four cohorts of patients in this study (please see below on study procedures). To be able to have meaningful data showing statistical significance, we will need at least 30 patients in each cohort of patients, accounting for There will be at least 30 patients in each cohort. We will need at least 100 patients enrolled in the study prior to randomization of the non-responders into early switch (\~30) or late switch (\~30) or non-switch (\~30). The estimated number also accounts for the estimated number of patients who will be lost to follow-up or may drop out.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uptown Eye Specialists
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sohel Somani, Uptown Eye Specialists
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04856397
- Sponsor's protocol ID
- 00001
- Acronym
- DME
- Status last verified
- May 2021
- First submitted
- 29 Jun 2020
- Last updated
- 12 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ozurdex in Suboptimal Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT04856397
- Acronym / sponsor ID
- DME / 00001
- Conditions
- Diabetic Macular Edema
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Uptown Eye SpecialistsUniversity, hospital or other
- Study start
- 25 May 2021 (estimated)
- Primary completion
- 30 Aug 2021 (estimated)
- Study completion
- 29 Dec 2021 (estimated)
- First posted
- 23 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary focus of this study is to understand the anatomic and visual outcomes of patients with refractory and suboptimal treatment response diabetic macular edema (DME) using anti-vascular endothelial growth factor (VEGF) to Ozurdex, an intravitreal dexamethasone implant. Secondly, investigators aim to understand the differences in cytokine profiles in patients who respond differently to intravitreal anti-VEGF versus Ozurdex. The importance of this study is to identify biomarkers that may help predict patients' response to different treatment protocols. Currently, Ozurdex is not covered by provincial health benefit plans for patients with DME. Our results may help improve access to care for those who have suboptimal results with or refractory to intravitreal anti-VEGF treatment.
Detailed description
Diabetic macular edema (DME) is the most common cause of vision loss in young patients with diabetes. Its pathophysiology starts with decreased retinal oxygen tension that manifests as retinal capillary hyperpermeability and increased intravascular pressure mediated by vascular endothelial growth factor (VEGF) upregulation and retinal vascular autoregulation, respectively. Spectral domain optical coherence tomography (SD-OCT) is the cornerstone of clinical assessment of DME. The foundation of treatment is metabolic control of hyperglycemia and blood pressure. Specific ophthalmic treatments of DME include intravitreal anti-VEGF drug injections, in the form of intravitreal Bevacizumab (Avastin), Ranibizumab (Lucentis), and Aflibercept (Eylea). Intravitreal corticosteroid injections, focal laser photocoagulation, and vitrectomy are other treatment options. A substantial fraction of eyes respond incompletely to all of these modalities resulting in visual loss and disordered retinal structure and vasculature visible on SD-OCT and OCT angiography. There is currently no consensus on when to switch from one treatment to another in the context of a suboptimal response. Our hypothesis is that patients who are switched early to Ozurdex and achieve an OCT proven dry state, achieve better functional outcomes than those patients who are switched late or not at all, by limiting exposure of the retina to potentially damaging inflammatory markers, and the merits associated with less frequent injections.
Suboptimal DME is defined as a central subfoveal retinal thickness of > 300 and the presence of intra or sub-retinal fluid with a minimum BCVA of 20/25 or worse after 3 injections of intravitreal aflibercept, from here on referred to as Eylea. Furthermore, there is some evidence that a subset of patients with refractory DME respond well to intravitreal corticosteroids, specifically, Ozurdex, which is a biodegradable, sustained-release intravitreal dexamethasone implant, designed to be potentially injected between 2-6 months. This medication is currently not covered by the Ontario health benefits plan for patients with DME and comes at a significant cost to patients.
Moreover, recent studies have confirmed the important role of inflammatory ocular cytokines in patients' response to intravitreal treatments in DME, much the same as neovascular age-related macular degeneration. However, it is not known which ocular cytokines determine the degree of response to various treatment modalities for DME.
Here, investigators aim to study the anatomic and visual outcomes, as well as the cytokine profile of patients with suboptimal DME in response to early vs. late switch to intravitreal Ozurdex treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- There are four cohorts of patients in this study (please see below on study procedures). To be able to have meaningful data showing statistical significance, we will need at least 30 patients in each cohort of patients, accounting for There will be at least 30 patients in each cohort. We will need at least 100 patients enrolled in the study prior to randomization of the non-responders into early switch (~30) or late switch (~30) or non-switch (~30). The estimated number also accounts for the estimated number of patients who will be lost to follow-up or may drop out.
| Arm | Type | Receives |
|---|---|---|
| Control group | Other | Drug: EyleaResponders will be in this category. These patients will be maintained on intravitreal anti-VEGF therapy for 1 year, with a monthly PRN ("as needed") treatment regimen post 5 monthly loading doses. |
| Early switch | Experimental | Drug: Intravitreal Implant in Applicator, Drug: EyleaSuboptimal responders who are switched to intravitreal Ozurdex (monitored monthly and treated PRN at a potential 2-6 month interval) injections after the first 3 monthly loading intravitreal eylea. |
| Late switch | Experimental | Drug: Intravitreal Implant in Applicator, Drug: EyleaSuboptimal responders who are switched to intravitreal Ozurdex (monitored monthly and treated PRN at a potential 2-6 month interval) injections after the first 6 monthly loading intravitreal eylea |
| Non-switch | Other | Drug: EyleaSuboptimal responders who continue to receive monthly intravitreal anti-VEGF injections. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Treatment-native patients with DME secondary to type I or type II diabetes mellitus
- Patients who require intravitreal anti-VEGF treatment
- Able to understand English and complete a pain assessment
- Suboptimal DME responders in patients who have received 3 or 6 eylea injections (non-cytokine group)
Key exclusion criteria (4 listed)
- Deafness or communication disorder, known Dementia, Severe COPD/Asthma (severe lung disorder), Severe OSA, Psychiatric or Anxiety conditions, involuntary movement disorders, allergy to the anesthesia, any conditions requiring intraoperative iris manipulation, any prior ocular surgery; all patients who may need translation, are illiterate, or unable to provide consent.
- Pre-existing ocular pathology confounding outcome (i.e. uveitis, retinal vascular disease, macular degeneration etc.)
- Pre-existing uncontrolled glaucoma/high IOP
- Patients under 18
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 |
|---|---|---|
| Intravitreal Implant in ApplicatorAlso: OzurdexDexamethasone intravitreal implant | Drug | Early switch, Late switch |
| Eyleaanti-VEGF medication | Drug | Control group, Early switch, Late switch, Non-switch |
Primary outcome
Visual acuity
Time frame: 1 year
best corrected visual acuity (BCVA)
5 secondary outcomes
OCT findings
Time frame: 1 year
OCTa findings
Time frame: 1 year
Cytokine expression TNFa
Time frame: 1 year
Cytokine expression IL-8
Time frame: 1 year
Cytokine expression IL-6
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Intravitreal Implant in Applicator and Eylea in people with Diabetic Macular Edema, run by Uptown Eye Specialists.
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 4 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Results are not available in the source record.
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?
Visual acuity (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2021.