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Dexamethasone Intravitreal Implant for the Treatment of Persistent Diabetic Macular Edema (DIME)

Primary Purpose

Diabetic Macular Edema

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dexamethasone intravitreal implant (0.7 mg)
Intravitreal anti-VEGF injection
Sponsored by
California Retina Consultants
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macular Edema

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Able to provide written informed consent and comply with study assessments for the full duration of the study.
  • Age ≥ 18 years

  • Diagnosis of diabetes mellitus (type 1 or 2)

    • Any one of the following will be considered to be sufficient evidence that diabetes is present:
    • Current regular use of insulin for treatment of diabetes
    • Current regular use of oral anti-hyperglycemia agent for the treatment of diabetes
  • Clinical evidence of retinal thickening due to macular edema involving the center of the macula associated with diabetic retinopathy.
  • Previous history of anti-vegf treatment for diabetic macular edema (DME) with documented incomplete resolution of central subfield thickening by spectral-domain optical coherence tomography (SDOCT). At least 4 intravitreal anti-vegf injections within the past six months prior to the baseline study visit are required for eligibility.
  • Central diabetic macular edema present on clinical examination and SDOCT testing with central 1 mm subfield thickness greater than 300 microns as measured on SDOCT at the baseline visit.
  • Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 74 letters (20/32) by the ETDRS visual acuity protocol.
  • Media clarity, pupillary dilation and patient cooperation sufficient to allow SDOCT testing and retinal photography.

Exclusion Criteria:

  • Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception.
  • Participation in another ocular investigation or trial simultaneously
  • Blood pressure > 180/110 mmHg (systolic above 180 OR diastolic above 110 mmHg)
  • Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse)
  • Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema
  • An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy)
  • Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gass)
  • Evidence of active neovascularization of the iris or retina
  • Evidence of central atrophy or fibrosis in the study eye
  • Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study.
  • History of vitreous surgery in the study eye
  • History of cataract surgery within 3 months of enrollment.
  • History of YAG capsulotomy within 2 months of enrollment.
  • Visual acuity <20/400 on ETDRS visual acuity charts in the fellow eye
  • Uncontrolled glaucoma (pressure > 30 mmHg) despite treatment with glaucoma medications.
  • History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
  • Use of systemic steroids (eg, oral, intravenous, intramuscular, epidural, rectal, or extensive dermal) within one month prior to the baseline study visit

Sites / Locations

  • California Retina Consultants
  • California Retina Consultants
  • California Retina Consultants
  • California Retina Consultants

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Implant

Intravitreal anti-VEGF injection

Arm Description

Subjects randomized to dexamethasone intravitreal implant (0.7mg) will receive the initial treatment at Month 3 (visit 4) and Month 6 (visit 7) and are eligible to receive one additional dose at Month 9 (visit 10), Month 10 (visit 11) or Month 11 (visit 12) for persistent or recurrent macular edema documented on SDOCT. If dexamethasone intravitreal implant (0.7mg) is administered at Month 10 (visit 11) or Month 11 (visit 12) an additional safety study visit will be required at one to two months following Month 12 (visit 13). The investigator can withhold treatment with dexamethasone intravitreal implant (0.7mg) beginning at Month 9 if there is complete resolution of diabetic macular edema document on SDOCT.

Subjects randomized to continue on anti-vegf therapy will receive intravitreal anti-vegf injections at Month 3 (visit 4) Month 4 (visit 5) and Month 5 (visit 6). Beginning at Month 6 (visit 7), subjects who have received 6 intravitreal anti-vegf injections and continue to present with persistent diabetic macular edema defined as less than 10% reduction or any increase in CST compared to baseline values and CST is greater than 300 microns, will receive dexamethasone intravitreal implant (0.7mg) at Month 6 (visit 7) and Month 9 (visit 10). The follow-up period for all subjects will continue through 12 months from the baseline study visit.

Outcomes

Primary Outcome Measures

Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months
Mean change in central 1 mm sub-field thickness between baseline and 9 months as measured by Spectral Domain Optical Coherence Tomography (SDOCT).

Secondary Outcome Measures

Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months
Mean change in standardized best-corrected visual acuity between baseline and 9 months as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) testing. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified
Total Number of Treatments in Each Arm Between Baseline and 9 Months
Total number of treatments in each arm between baseline and 9 months.

Full Information

First Posted
June 11, 2015
Last Updated
January 29, 2019
Sponsor
California Retina Consultants
Collaborators
Allergan
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1. Study Identification

Unique Protocol Identification Number
NCT02471651
Brief Title
Dexamethasone Intravitreal Implant for the Treatment of Persistent Diabetic Macular Edema
Acronym
DIME
Official Title
Dexamethasone Intravitreal Implant (0.7mg) for the Treatment of Persistent Diabetic Macular Edema Following Intravitreal Anti-Vascular Endothelial Growth Factor Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
June 2015 (undefined)
Primary Completion Date
October 24, 2018 (Actual)
Study Completion Date
October 24, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
California Retina Consultants
Collaborators
Allergan

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Laser photocoagulation and intravitreal anti-vascular growth factor injections are commonly used treatment options for individuals with diabetic macular edema. However, some patients continue to experience persistent diabetic macular edema and poor vision despite continued laser and/or anti-vegf therapy. Recent clinical trials suggest that due to inflammatory mediators dexamethasone intravitreal implant (0.7mg) may be a good alternative therapy for individuals unresponsive to laser photocoagulation or intravitreal anti-vascular growth factor injections. The purpose of this research study is to compare the effectiveness of using a dexamethasone steroid implant versus monthly intravitreal anti-VEGF injections for research participants with persistent diabetic macular edema (DME).
Detailed Description
Macular edema is a major cause of central vision loss in patients presenting with diabetic retinopathy. Diabetic macular edema (DME) occurs when fluid leaks into the center of the macula, the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the macula swell, blurring vision. Diabetic macular edema (DME) affects between 8% to 10% of 23.6 million diabetic individuals in the United States. The prevalence of diabetic macular edema after 15 years of known diabetes is approximately 20% in patients with type 1 diabetes, 25% in patients with type 2 diabetes who are taking insulin, and 14% in patients with type 2 diabetes who do not take insulin. Within two years of diagnosis, nearly half of individuals with DME will lose 2 or more lines of visual acuity (the smallest line you can read on a standardized vision chart held 20 feet away). Diabetic macular edema is typically treated with laser and/or intravitreal injections of drugs such as anti-VEGF agents. Anti-VEGF agents block a protein that slows the growth of the abnormal blood vessels. Dexamethasone is a corticosteroid used to treat inflammation. Dexamethasone implant is a steroid implant injected into the eye to treat swelling that may occur when there is a blockage of certain blood vessels in your eyes. Both anti-VEGF agents and dexamethasone implant are approved by the FDA to treat DME. The purpose of this research study is to compare the effectiveness of using a dexamethasone steroid implant versus monthly intravitreal anti-VEGF injections for research participants with persistent diabetic macular edema (DME).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Macular Edema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Implant
Arm Type
Active Comparator
Arm Description
Subjects randomized to dexamethasone intravitreal implant (0.7mg) will receive the initial treatment at Month 3 (visit 4) and Month 6 (visit 7) and are eligible to receive one additional dose at Month 9 (visit 10), Month 10 (visit 11) or Month 11 (visit 12) for persistent or recurrent macular edema documented on SDOCT. If dexamethasone intravitreal implant (0.7mg) is administered at Month 10 (visit 11) or Month 11 (visit 12) an additional safety study visit will be required at one to two months following Month 12 (visit 13). The investigator can withhold treatment with dexamethasone intravitreal implant (0.7mg) beginning at Month 9 if there is complete resolution of diabetic macular edema document on SDOCT.
Arm Title
Intravitreal anti-VEGF injection
Arm Type
Active Comparator
Arm Description
Subjects randomized to continue on anti-vegf therapy will receive intravitreal anti-vegf injections at Month 3 (visit 4) Month 4 (visit 5) and Month 5 (visit 6). Beginning at Month 6 (visit 7), subjects who have received 6 intravitreal anti-vegf injections and continue to present with persistent diabetic macular edema defined as less than 10% reduction or any increase in CST compared to baseline values and CST is greater than 300 microns, will receive dexamethasone intravitreal implant (0.7mg) at Month 6 (visit 7) and Month 9 (visit 10). The follow-up period for all subjects will continue through 12 months from the baseline study visit.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone intravitreal implant (0.7 mg)
Other Intervention Name(s)
Ozurdex
Intervention Description
Subjects with persistent DME who are randomized to this arm may get up to 3 treatments with the implant (0.7 mg dexamethasone).
Intervention Type
Drug
Intervention Name(s)
Intravitreal anti-VEGF injection
Other Intervention Name(s)
ranibizumab, bevacizumab, or aflibercept
Intervention Description
This injection may be ranibizumab, bevacizumab, or aflibercept.
Primary Outcome Measure Information:
Title
Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months
Description
Mean change in central 1 mm sub-field thickness between baseline and 9 months as measured by Spectral Domain Optical Coherence Tomography (SDOCT).
Time Frame
baseline and 9 months
Secondary Outcome Measure Information:
Title
Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months
Description
Mean change in standardized best-corrected visual acuity between baseline and 9 months as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) testing. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified
Time Frame
baseline and 9 months
Title
Total Number of Treatments in Each Arm Between Baseline and 9 Months
Description
Total number of treatments in each arm between baseline and 9 months.
Time Frame
baseline and 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to provide written informed consent and comply with study assessments for the full duration of the study. Age ≥ 18 years Diagnosis of diabetes mellitus (type 1 or 2) Any one of the following will be considered to be sufficient evidence that diabetes is present: Current regular use of insulin for treatment of diabetes Current regular use of oral anti-hyperglycemia agent for the treatment of diabetes Clinical evidence of retinal thickening due to macular edema involving the center of the macula associated with diabetic retinopathy. Previous history of anti-vegf treatment for diabetic macular edema (DME) with documented incomplete resolution of central subfield thickening by spectral-domain optical coherence tomography (SDOCT). At least 4 intravitreal anti-vegf injections within the past six months prior to the baseline study visit are required for eligibility. Central diabetic macular edema present on clinical examination and SDOCT testing with central 1 mm subfield thickness greater than 300 microns as measured on SDOCT at the baseline visit. Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 74 letters (20/32) by the ETDRS visual acuity protocol. Media clarity, pupillary dilation and patient cooperation sufficient to allow SDOCT testing and retinal photography. Exclusion Criteria: Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception. Participation in another ocular investigation or trial simultaneously Blood pressure > 180/110 mmHg (systolic above 180 OR diastolic above 110 mmHg) Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse) Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy) Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gass) Evidence of active neovascularization of the iris or retina Evidence of central atrophy or fibrosis in the study eye Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study. History of vitreous surgery in the study eye History of cataract surgery within 3 months of enrollment. History of YAG capsulotomy within 2 months of enrollment. Visual acuity <20/400 on ETDRS visual acuity charts in the fellow eye Uncontrolled glaucoma (pressure > 30 mmHg) despite treatment with glaucoma medications. History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0. Use of systemic steroids (eg, oral, intravenous, intramuscular, epidural, rectal, or extensive dermal) within one month prior to the baseline study visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriel Gordon, Ph.D.
Organizational Affiliation
California Retina Consultants
Official's Role
Study Director
Facility Information:
Facility Name
California Retina Consultants
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
California Retina Consultants
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
California Retina Consultants
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93103
Country
United States
Facility Name
California Retina Consultants
City
Santa Maria
State/Province
California
ZIP/Postal Code
93454
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30293228
Citation
Chakravarthy H, Devanathan V. Molecular Mechanisms Mediating Diabetic Retinal Neurodegeneration: Potential Research Avenues and Therapeutic Targets. J Mol Neurosci. 2018 Nov;66(3):445-461. doi: 10.1007/s12031-018-1188-x. Epub 2018 Oct 6.
Results Reference
derived

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Dexamethasone Intravitreal Implant for the Treatment of Persistent Diabetic Macular Edema

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