Clinical trial NCT03751501: Targeted Laser in Diabetic Macular Edema
Official title: Photocoagulation of Capillary Macro-aneurysms in Addition to the Standard Treatment of Macular Edema Due to Diabetic Retinopathy. "TaLa_DME"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Macular Edema
Diabetic Retinopathy
Lead sponsor: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Sponsor class: OTHER
First posted: 2018-11-23
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible participants will be randomized into one of the 2 study arms groups: "standard of care" group with sham laser or experimental group with laser.

Both group with laser or sham laser will be performed in combination with anti VEGF treatment
Primary purpose: PREVENTION

Brief summary: Our hypothesis is that implementing laser photocoagulation (IGTL) as an adjunctive treatment to intravitreal injections should lead to a significant reduction in the need for intravitreal injections in patients with diabetic macular edema without adverse consequences for visual acuity.

Detailed description: This study will be French, multicenter parallel group, 2-arms, randomized, sham laser-controlled, double-blind trial evaluating the effect of IGTL as an adjunctive procedure to intravitreal injections in patients with DME.

Acts which are the subject of the study: indocyanine green-Guided Targeted Laser photocoagulation (IGTL): this combines routine procedures, that are, the detection of macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser verification of the effectiveness of the photothrombosis by OCT.

Study act: the treatment study includes a baseline laser treatment (experimental group) or sham laser (control group) at randomization, repeated if needed 3 month later, administered in combination with anti VEGF treatment, consisting of 3 monthly injections in the first 3 months, and a maintenance phase with monthly visits where retreatment is administered as needed through a PRN regimen, based on morphological (retinal thickness on OCT) and functional (visual acuity) criteria.

To evaluate the interest of IGTL in real conditions, the choice of the anti VEGF treatment used for intravitreal injection (Ranibizumab or Aflibercept, which have French marketing authorizations) is left to each investigator (equivalent therapeutic efficacy). Bevacizumab is ruled out due to its lower efficacy compared with Aflibercept among eyes with worse baseline VA, that represent the majority of the patients in our study. In addition, bevacizumab is currently off-label in France for DME If both eyes are eligible at the time of randomization, only one eye will be included and analyzed. However, the fellow eye will be treated with the randomization-assigned treatment and the testing will be performed on each eye.

Risks and constraints involved in the study: these procedures are commonly done in ophthalmology care settings; no additional risk is expected due to the study.

Expected benefits for the participants and for the company: These procedures are commonly done in ophthalmology care settings; no additional risk is expected due to the study.

Eligibility criteria: Inclusion Criteria:

* Diabetic women and men ≥18 years
* with visual acuity lower or equal than 20/32 ( ≤ 74 TaLaDME protocol_v1.2_12.07.2018 9/76 ETDRS letters)
* with central retinal thickness of more than 300μm in Spectral Domain OCT (SD-OCT) and/or presence of retro-foveal hard exudates
* due to DME
* with one or more macro-aneurysms with a diameter greater than 150 μm in the posterior pole
* with health insurance
* who signed the written informed consent form

Exclusion Criteria:

* Presence of age-related drusens or of a macular degeneration in one or both any eyes
* Significant opacity of the ocular media that could contribute to decreased visual acuity
* macro-aneurysm(s) mainly responsible for the DME located less than 500μm from the center of the fovea (i.e. within 1 disc radius of the fovea),
* Steroids injection within the last 4 months
* proliferative diabetic retinopathy requiring panretinal photocoagulation or associated with posterior tractional retinal detachment that may be worsened by the use of anti-VEGF therapy
* myocardial infarction or stroke within the last 3 months
* Cataract surgery within the last 3 months
* Local treatment with prostaglandin
* Women who are pregnant, breast feeding or of child bearing age without effective contraception

Primary outcomes:
measure: Number of anti VEGF injections
timeFrame: 12months
measure: Change in Visual Acuity (Letters)
timeFrame: 12 months
Secondary outcomes:
measure: Change in central macular thickness
timeFrame: 12 months
measure: Cost of treatment
timeFrame: 12 months
measure: Incremental cost-utility ratio
timeFrame: 12 months
measure: Impact on quality of life using standard score evolution
timeFrame: 12 months
measure: Number of AEs/SAEs
timeFrame: 36 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Study officials:
affiliation: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
name: Michel PAQUES, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: