Efficacy Comparison of DExamethasone Intravitreal Implant Combined With Aflibercept Versus Aflibercept Monotherapy in Treatment-naïve Inflammatory Diabetic Macular Edema Patients

NCT07438119 — Phase 4, Not yet recruiting, 114 participants, Kun Liu

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Efficacy Comparison of DExamethasone Intravitreal Implant Combined With Aflibercept Versus Aflibercept Monotherapy in Treatment-naïve Inflammatory Diabetic Macular Edema Patients (DECADE Study)

Registry	NCT07438119, acronym DECADE
Status	Not yet recruiting
Phase	Phase 4
Study type	Interventional; randomized, parallel, masking: single, treatment
Enrollment	114 (Estimated)
Sponsor	Kun Liu (Other); collaborators: The Second Affiliated Hospital of Harbin Medical University, Peking University People's Hospital, The General Hospital of Central Theater Command, First Affiliated Hospital of Fujian Medical University, Zhongshan Ophthalmic Center, Sun Yat-sen University, Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, The First Affiliated Hospital of Dalian Medical University, West China Hospital, The First People's Hospital of Xuzhou
Conditions	Diabetic Macular Edema (DME)
Interventions	Combination Therapy with Aflibercept Intravitreous Injection (2mg) and Dexamethasone Intravitreal Implant, Aflibercept Intravitreous Injection (2mg) Monotherapy (Drug)
Dates	start 2026-03-15 (estimated), primary completion 2027-09-15 (estimated), completion 2028-03-15 (estimated), first posted 2026-02-27, last updated 2026-02-27

-Summary

This is a 12-month, prospective, randomized controlled, multi-center, open-label, superiority designed study. Treatment-Naïve DME patient with inflammatory biomarkers, who meet the inclusion and exclusion criteria, will be recruited.

This study aims to provide the first direct comparative evidence within a Chinese cohort, evaluating the efficacy and safety of a combined DEX-I plus aflibercept therapy versus aflibercept monotherapy for DME. The investigation will focus on functional visual outcomes, anatomical improvements, and the respective safety profiles associated with each treatment regimen. Furthermore, the study will incorporate specific optical coherence tomography (OCT) biomarkers to refine patient selection, with the goal of enhancing the precision of identifying candidates for combination therapy.

It is hypothesized that the combination therapy, by concurrently targeting both VEGF-mediated and inflammatory pathways, may yield superior clinical outcomes compared to monotherapy.

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+Arms and interventions

Arm	Type	Interventions	Description
Control Group [Anti-VEGF Monotherapy]	Other	Drug: Aflibercept Intravitreous Injection (2mg) Monotherapy	Control Group: Eyes will be administered monthly intravitreal aflibercept during the first 3 months, followed by pro re nata (PRN) regimen from Month 3-12. • Re-treatment criteria: CMT ≥300 μm and/or BCVA decline ≥5 letters from the last-recorded measurement.
Intervention Group (Combination Therapy with Anti-VEGF and DEX-I)	Experimental	Drug: Combination Therapy with Aflibercept Intravitreous Injection (2mg) and Dexamethasone Intravitreal Implant	Intervention Group: Eyes will be administered monthly intravitreal aflibercept for the first 3 months while the first Dexamethasone Intravitreal Implant (DEX-I) be administered within a 2-week window of the first aflibercept injection. Between Month 3-12, aflibercept and DEX-I will be administered using PRN regimen based on pre-defined re-treatment criteria. * Re-treatment criteria: CMT ≥300 μm and/or BCVA decline ≥5 letters from the last-recorded measurement. * Treatment selection: 1. If the treatment interval since the last DEX-I injection is <5 months, administer aflibercept alone. 2. If the treatment interval since the last DEX-I injection ≥5 months, administer DEX-I plus aflibercept within a 2-week window.

Combination Therapy with Aflibercept Intravitreous Injection (2mg) and Dexamethasone Intravitreal Implant (Drug): This group shall receive a combination of Aflibercept Intravitreous Injection (2 mg) and the Dexamethasone Intravitreal Implant (DEX-I, 0.7 mg).
Aflibercept Intravitreous Injection (2mg) Monotherapy (Drug): This group shall be designated to receive Aflibercept Intravitreous Injection at the recommended dose of 2 mg as a standalone treatment. (standard treatment)

+Outcome measures

Primary outcomes

Change in central macular thickness (CMT) of each group from baseline to the end at Month 6. [From baseline to Month 6.]

Secondary outcomes

Change in central macular thickness (CMT) of each group from baseline to Month 3 and 12. [From baseline to Month 3 and 12.]
Change in best corrected visual acuity (BCVA) of each group from baseline to Month 3, 6, and 12. [From baseline to Month 3, 6, and 12.]
Proportion of eyes with a 10-letter/15-letter BCVA improvement from baseline to month 3, 6, 12. [From baseline to month 3, 6, 12.]
Change in OCT biomarkers (SRD, HRD, HE, large IRC) from baseline to Month 6 and 12. [From baseline to Month 6 and 12.]
Treatment burden of each group measured as the number of intravitreal injections during the study. [From baseline to Month 12]
Safety and tolerability of each group assessed by the incidence of ocular and systemic adverse events. [From baseline to Month 12]

Other outcomes

Change in the non-perfused area (NPA) of the peripheral retina from baseline to Month 6, 12. [From baseline to Month 6, 12.]
Changes in macular FAZ area by OCTA from baseline to Months 6 and 12. [From baseline to Month 6, 12]
Changes in macular vessel density by OCTA from baseline to Months 6 and 12. [From baseline to Month 6, 12]
Change in Diabetic Retinopathy Severity Scale (DRSS) score (recording the proportion of patients with regression ≥1 step and ≥2 steps) from baseline to Months 6 and 12. [From baseline to Month 6, 12]

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

All of the following conditions must be met simultaneously:

1. Age ≥ 18 years, diagnosis of diabetes mellitus (type Ⅰor type Ⅱ).
2. With good glycaemic control and glycated haemoglobin ≤10.0%.
3. DR stage II-IV.
4. Treatment with aflibercept intravitreal injection is planned for center-involved diabetic macular edema (CI-DME) , Central macular thickness (CMT) ≥300 μm in the 1-mm-diameter zone around fovea with best corrected visual acuity(BCVA) <20/25.
5. Presence on OCT imaging of one or more of the following findings in the study eye(within 1000-μm-diameter of the center of the fovea): central macular thickness (CMT) ≥500μm, foveal intraretinal cystoid spaces ≥300μm in height or ≥250μm in width(large IRC), serous retinal detachment (SRD), Intraretinal hyperreflective dots (HRDs), Hard exudates (HEs).
6. No refractive interstitial clouding and pupillary constriction affecting fundus examination.

Exclusion Criteria:

1. Grade III and IV cataracts, or those with post-comorbid subcapsular cataracts,
2. Other macular degeneration such as Macular epiretinal membrane and Macular Hole, etc., or macular edema caused by other causes such as uveitis, retinal vein occlusion, etc.,
3. Combined with diabetic optic neuropathy,
4. Any prior use of an approved or investigational treatment for DME in the study eye such as anti-VEGF drugs or corticosteroids drugs etc.,
5. History of vitreoretinal surgery and/or including scleral buckling in the study eye,
6. Transscleral fixated IOLs and ruptured posterior lens capsule,
7. Active or suspected ocular and periocular infections,
8. Advanced glaucoma or uncontrolled glaucoma with anti-glaucoma drugs; Or a history of glucocorticoid-induced elevated intraocular pressure,
9. Systemic conditions such as asthma, severe hypertension, cerebrovascular accident or myocardial infarction, or other reasons for not being able to co-operate with the relevant examination,
10. Pregnant or lactating,
11. Patients with hypersensitivity to dexamethasone or to any other components of the product,
12. Patients are allergic to aflibercept or any of the ingredients Aflibercept Intravitreous Injection.