Evaluation of Month-24 Efficacy and Safety of Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration: The MERLOT Randomized Clinical Trial
NCT01006538 | MERLOT Trial | Jackson TL et al. (2020)
Jackson TL, Soare C, Petrarca C, et al. Evaluation of Month-24 Efficacy and Safety of Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration: The MERLOT Randomized Clinical Trial. JAMA Ophthalmology, 2020; 138(8):835-842.
Locations
24 National Health Service hospitals in the United Kingdom
Study Period
November 2009 – January 2012
Study Design
Randomized, open-label, multicenter, parallel-group comparative trial
Study Population
Experimental Group
Control Group
Follow-up Time: 24 months
Outcomes
Durability
Number of Injections Mean number of ranibizumab injections from month 1 to month 24 (co-primary outcome):
• EMB + ranibizumab: 9.3 ± 6.7
• Ranibizumab monotherapy: 8.3 ± 4.5
• Difference: 1.0 injection (95% CI, -0.3 to 2.3; p = 0.13)
Vision
Best-Corrected Visual Acuity (BCVA) Mean change in BCVA (ETDRS letters) at Month 24 (co-primary outcome):
• EMB + ranibizumab: -11.2 ± 15.7
• Ranibizumab monotherapy: -1.4 ± 10.9
• Difference: -9.8 letters (95% CI, -6.7 to -12.9; p < 0.001) Vision Maintaining The proportion of patients losing <15 ETDRS letters at Month 24:
• EMB + ranibizumab: 65.6%
• Ranibizumab monotherapy: 86.6%
• Difference: -21% (95% CI: -29.5% to -12.4%; p < 0.001) The proportion of patients gaining 0 or more ETDRS letters at Month 24:
• EMB + ranibizumab: 28.3%
• Ranibizumab monotherapy: 51.3%
• Difference: 23% (95% CI: 12.4% to 33.6%); p <0.001 The proportion of patients gaining ≥15 ETDRS letters:
• EMB + ranibizumab: 0.8%
• Ranibizumab monotherapy: 3.4%
• Difference: -2.6% (95% CI: -6.0% to 0.9%; p = 0.03)
Other
N/A
Immunognicity
Not reported.
Pharmokinetics
Not reported.
Anatomic
Angiographic Lesion Mean change in total lesion size (mm²) at Month 24:
• EMB + ranibizumab: +4.1 ± 8.7
• Ranibizumab monotherapy: +2.1 ± 5.8
• Difference: 2.0 mm² (95% CI: 0.04 to 3.9; p = 0.05) Foveal Thickness The mean change in foveal thickness (µm) at Month 24:
• EMB + ranibizumab: +7.0 ± 193
• Ranibizumab monotherapy: -20.0 ± 130
• Difference: 27µm (95% CI: -14.8 to 68.8; p = 0.19) Choroidal Neovascularization (CNV) Mean change in CNV size (mm²) at Month 24:
• EMB + ranibizumab: +2.6 ± 10.0
• Ranibizumab monotherapy: +0.04 ± 6.3
• Difference: 2.6 mm² (95% CI, 0.3 to 4.7); p = 0.02.
Safety
Ocular AEs Total events:
• EMB + ranibizumab: 477
• Ranibizumab monotherapy: 94 Patients with clinically significant cataracts over 24 months:
• EMB + ranibizumab: 66.0% (161/244)
• Ranibizumab monotherapy: 20.2% (24/119) Patients with investigator-reported reduced VA over 24 months:
• EMB + ranibizumab: 12.3% (30/244)
• Ranibizumab monotherapy: 5.0% (6 of 119) Patients with microvascular abnormalities (MVAs) over 24 months:
• EMB + ranibizumab: 9.7% (20/207)
• Ranibizumab monotherapy: 1.0% (1 of 97) Non-ocular AEs Total events:
• EMB + ranibizumab: 729
• Ranibizumab monotherapy: 319
• Most common: Cardiac disorders, Ear and labyrinth disorders, Endocrine disorders, Eye disorders, Gastrointestinal disorders Serious AEs (SAEs) Total events of ocular SAEs:
• EMB + ranibizumab: 19
• Ranibizumab monotherapy: 3 Total events of non-ocular SAEs:
• EMB + ranibizumab: 276
• Ranibizumab monotherapy: 115 Death
• EMB + ranibizumab: 3.7% (9/244)
• Ranibizumab monotherapy: 3.4% (4 of 119)
Conclusion
EMB did not reduce the number of ranibizumab injections and was associated with worse visual acuity compared to ranibizumab monotherapy. The MERLOT trial does not support EMB as an adjunct treatment for chronic neovascular AMD.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “A commercially available system (MedSciNet Studies; MedSciNet AB)was used for randomization.”
Missing Outcome Data
Low risk
Note: The evidence of the primary outcome was not biased by the missingness (Imputation): “Multiple imputation was performed for 36 participants with missing month-24 BCVA.”
Selection of the Reported Results
Low risk Note: protocol publically available.
Deviations from Intended Observations
Some concerns Note: “Masking of participants and clinicians was not possible, but the assessment of BCVA and imaging were masked.” There is no information on whether the deviation arose due to the true value. “Data analysis followed the intent-to-treat approach…”
Measurement of the Outcome
Some concerns Note: “Masking of participants and clinicians was impossible, but the assessment of BCVA and imaging were masked.” This is a multiple-site study. The BCVA measurement may be different among different sites.
Overall
concerns
Categories: Wet AMD