Evaluation of Fluocinolone Acetonide Versus Dexamethasone Intravitreal Implants in Resistant Diabetic Macular Edema in Pseudophakic Patients

The primary objective of this study is to assess the **cost-utility ratio** at 3 years of treatment with **fluocinolone acetonide** (FA) intravitreal implant compared with treatment with **dexamethasone** (DXM) intravitreal implant in the management of resistant **Diabetic Macular Oedema** (DME) in pseudophakic patients, from a societal perspective. This evaluation is clinically relevant as it aims to determine the economic value of these treatments, which is crucial for healthcare decision-making and resource allocation.

Secondary objectives include:

• Comparing the effectiveness of treatments in terms of mean change in best corrected visual acuity (BCVA) over various periods and specific time points.
• Assessing the rate of patients with an improvement in BCVA by ≥ 15 letters and those achieving at least 80 letters of BCVA at specified intervals.
• Evaluating the mean change in central foveolar retinal thickness at 12, 24, and 36 months.
• Analyzing treatment regimens and additional treatments.
• Comparing the effect of treatments on quality of life and the safety of treatments in terms of adverse events occurrence.
• Assessing the cost-effectiveness impact over 3 years of FA implants compared with DXM implants from a societal viewpoint.
• Evaluating the budgetary impact over 5 years of generalizing FA treatment in France on the compulsory health insurance budget.

The clinical trial involves participants diagnosed with **Diabetic Macular Oedema**. The study population includes both male and female subjects aged 18 years and older. Participants are required to be in general good health, with specific inclusion criteria focusing on those with a central foveolar thickness greater than 300 microns, despite at least two years of prior treatment. The trial targets pseudophakic patients who have undergone cataract surgery more than six months prior and have experienced a decrease in visual acuity. Participants must have previously received at least one effective dexamethasone injection and an anti-VEGF injection within specified time frames. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the **cost-utility ratio** of two intravitreal implants, **fluocinolone acetonide** and **dexamethasone**, in the treatment of resistant **diabetic macular oedema** in pseudophakic patients. This is a randomized, double-blind, controlled trial with a duration of 36 months. The primary objective is to assess the cost per year of life gained in good health, expressed as cost per quality-adjusted life year (QALY). Secondary endpoints include changes in best-corrected visual acuity (BCVA), central retinal thickness, treatment regimen, quality of life scores, and adverse events.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, previous treatment history, and visual acuity. Follow-up visits will occur at regular intervals, including 12, 24, and 36 months, to monitor BCVA, central retinal thickness, and other health parameters. The end-of-study visit will conclude the trial, summarizing the participant's health outcomes and treatment efficacy.

The expected length of participant involvement is up to 36 months, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial aims to provide comprehensive data on the economic and clinical effectiveness of the two treatments, contributing valuable insights into the management of diabetic macular oedema.

The clinical trial involves the use of two **intravitreal implants** for the treatment of resistant diabetic macular edema in pseudophakic patients. The first experimental medication is **ILUVIEN**, which contains **fluocinolone acetonide** as the active substance. This medication is provided as an **intravitreal implant** with an applicator, designed for direct administration into the vitreous cavity of the eye. The implant delivers a total dose of 190 micrograms of fluocinolone acetonide, with a maximum treatment period of 36 months. The administration route is strictly intravitreal, and the medication is classified under anti-inflammatories and corticosteroids, not combined. Compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the treatment's efficacy and safety.

The comparator treatment in the study is **OZURDEX**, which contains **dexamethasone** as the active ingredient. Similar to ILUVIEN, OZURDEX is also provided as an **intravitreal implant** in an applicator, intended for intravitreal use. The implant delivers a total dose of 700 micrograms of dexamethasone, with a maximum treatment period of 36 months. This medication is categorized under anti-inflammatories. The administration and dosing schedule are closely monitored to ensure participant compliance and to facilitate a comprehensive evaluation of the treatment outcomes. Both medications are chemically derived and are not formulated for pediatric use. The trial aims to compare the cost-utility ratio of these treatments over a three-year period from a societal perspective.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the incremental cost-utility ratio at 3 years, expressed in terms of cost per year of life gained in good health (cost/QALY), from a societal perspective. Secondary endpoints include several measures of visual acuity and retinal thickness. **Best Corrected Visual Acuity (BCVA)** will be measured using the ETDRS scale at each follow-up visit, including at inclusion, with assessments at 12, 24, and 36 months. The analysis will involve constructing the average variation using the AUC approach over the 0-12 month, 0-24 month, and 0-36 month periods, as well as the difference between inclusion and subsequent time points. Additional secondary endpoints include central retinal thickness measured by optical coherence tomography, treatment regimen details, additional ophthalmological treatments, and VFQ-25 quality of life scores at baseline and at 12, 24, and 36 months. Adverse events, such as ocular hypertonia, endophthalmitis, and retinal detachment, will also be monitored at these intervals. The incremental cost-effectiveness ratio will be evaluated in terms of cost per life-year gained, cost per case of visual impairment avoided, and cost per case of legal blindness avoided. The net financial impact on the health insurance budget will also be assessed. These efficacy parameters will be collected and analyzed at specified time points throughout the trial duration, which is estimated to end on April 28, 2030.