Clinical trial NCT02471651: Dexamethasone Intravitreal Implant for the Treatment of Persistent Diabetic Macular Edema
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Macular Edema
Lead sponsor: California Retina Consultants
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2015-06-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months
timeFrame: baseline and 9 months
Secondary outcomes:
measure: Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months
timeFrame: baseline and 9 months
measure: Total Number of Treatments in Each Arm Between Baseline and 9 Months
timeFrame: baseline and 9 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Oxnard
country: United States
facility: California Retina Consultants
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants
state: California
Study officials:
affiliation: California Retina Consultants
name: Gabriel Gordon, Ph.D.
role: STUDY_DIRECTOR
References:
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.