Intravitreal sirolimus for persistent, exudative age-related macular degeneration: A Pilot Study
NCT02357342 | Not reported | Minturn RJ et al. (2021)
Minturn, R. J., Bracha, P., Klein, M. J., Chhablani, J., Harless, A. M., & Maturi, R. K. Intravitreal sirolimus for persistent, exudative age-related macular degeneration: A Pilot Study. Int J Retin Vitr, 2021; 7:11.
Locations
Single-center study in the United States
Study Period
April 2015 – January 2016
Study Design
Prospective, subject-masked, randomized controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: 6 Months
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA) Mean BCVA change at 6 months:
• Anti-VEGF = +4.9 letters
• Sirolimus = +2.3 letters
• Difference not statistically significant
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Central Subfield Thickness (CST)
Mean CST change from baseline to Month 6:
• Anti-VEGF = +20 µm
• Sirolimus = -40 µm
• T-test: p = 0.03
Retinal Fluid
Mean change of intraretinal fluid area (IRF) from baseline to Month 6:
• Anti-VEGF = +0.066 mm²
• Sirolimus = -0.115 mm²
• T test: p = 0.75
Mean change of subretinal fluid area (SRF) from baseline to Month 6:
• Anti-VEGF = +0.355 mm²
• Sirolimus = -0.713 mm²
• T test: p = 0.04
Choroidal Neovascularization (CNV)
The mean change in central choroidal neovascularization area:
• Anti-VEGF = +0.310 mm²
• Sirolimus = -0.538 mm²
• T test: p = 0.09
Safety
Minor AEs The number of ocular AE:
• Anti-VEGF = 7
• Sirolimus = 7
The number of ocular AE:
• Anti-VEGF = 8
• Sirolimus = 3
Serious AEs (SAEs) The number of ocular AE:
• Anti-VEGF = 0
• Sirolimus = 3
The number of ocular AE:
• Anti-VEGF = 1 (Hospitalization due to pulmonary embolism)
• Sirolimus = 3 (Two deaths due to pneumonia and pulmonary embolism, and one hospitalization due to a myocardial infection)
Conclusion
Intravitreal sirolimus monotherapy showed anatomical improvements in persistent, exudative AMD but was associated with notable ocular and systemic adverse events. Further studies are needed to evaluate its role as an adjunct therapy.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: No information was supplied on the method of the allocation concealment. However, “The baseline summary information summarizes the two study populations at their entry into the study. There was no statistical significance shown between our two study groups.”
Missing Outcome Data
Low risk
Note: Evidence that the result was not biased by missing outcome data (sensitivity analysis): “After adjusting for confounding variables, the adjusted change in CST and was found to be statistically significant as well.”
Selection of the Reported Results
Low risk Note: have registration with protocol.
Deviations from Intended Observations
Low risk Note: This is a double-masked study. “The 6-month evaluation was performed in 20 (100%) of the eyes in the anti-VEGF group and 18 (90%) of the eyes in the sirolimus group. During the study, two of the subjects died in the sirolimus group, one from pneumonia and the other from a pulmonary embolism.” -a mITT principle.
Measurement of the Outcome
Low risk Note: This is double masked study. In addition, this is a single site study. “…were calculated by an independent, masked OCT reader.”
Overall
Some Concerns
Categories: Wet AMD