Pagoda
Trial question
Is port delivery system with ranibizumab noninferior to monthly ranibizumab in patients with diabetic macular edema?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 634
634 patients (271 female, 363 male).
Inclusion criteria: treatment-naïve adult patients with center-involved diabetic macular edema.
Key exclusion criteria: high-risk proliferative diabetic retinopathy; active intraocular inflammation; ocular or periocular infection of either eye; uncontrolled ocular hypertension or glaucoma; cerebrovascular accident or MI within 6 months prior to randomization; AF diagnosis or worsening within 6 months prior to randomization; uncontrolled BP.
Interventions
N=381 continuous ranibizumab with port delivery system (ranibizumab 100 mg/mL via port delivery system with refill exchanges every 24 weeks).
N=253 monthly ranibizumab (intravitreal injections of ranibizumab 0.5 mg every 4 weeks).
Primary outcome
Mean improvement in best-corrected visual acuity averaged over weeks 60-64
9.6
9.4
9.6 letters
7.2 letters
4.8 letters
2.4 letters
0.0 letters
Continuous ranibizumab with port delivery
system
Monthly
ranibizumab
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in mean improvement in best-corrected visual acuity averaged over weeks 60-64 (9.6 letters vs. 9.4 letters; AD 0.2 letters, 95% CI -1.2 to 1.6).
Secondary outcomes
No significant difference in mean improvement of ≥ 2 in Diabetic Retinopathy Severity Score at week 64, efficacy population (39% vs. 41.9%; ARD -2.9, 95% CI -10.7 to 4.9).
No significant difference in mean reduction in central subfield thickness at week 64 (203.5 mcm vs. 199.7 mcm; AD 3.8 mcm, 95% CI -9.6 to 17.2).
No significant difference in mean improvement of ≥ 2 in Diabetic Retinopathy Severity Score at week 64, modified intention-to-treat population (41.6% vs. 41.6%; AD 0.1%, 95% CI -9 to 9.1).
Safety outcomes
No significant difference in ≥ 1 serious nonocular adverse events.
Significant difference in adverse events of special interest (27.5% vs. 8.9%).
Conclusion
In treatment-naïve adult patients with center-involved diabetic macular edema, continuous ranibizumab with port delivery system was noninferior to monthly ranibizumab with respect to mean improvement in best-corrected visual acuity averaged over weeks 60-64.
Reference
Arshad M Khanani, Peter A Campochiaro, Jordan M Graff et al. Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema: The Pagoda Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):326-335.
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