A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration
NCT02802657 | TREX | Jia H et al. (2022)
Jia, H., Lu, B., Yuan, Y., Yuan, F., Li, L., Song, Y., Rong, A., Zhou, M., Wang, F., Sun, X. A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration. Front Med, 2022; 9:852519.
Locations
5 centers in China
Study Period
July 2016 – August 2018
Study Design
Randomized, multicenter, non-inferiority trial
Study Population
Experimental Group
Control Group
Follow-up Time: 24 months
Outcomes
Durability
Number of Injections
The mean number of injections at 24 months:
• T&E = 14.6 (SD 4.1)
• PRN = 12.4 (SD 6.1)
• Difference = +2.2 (p = 0.041).
Number of Visits
The mean number of visits at 24 months:
• T&E = 15.4 (SD 3.8)
• PRN = 23.1 (SD 3.5)
• Difference = -7.7 (p < 0.001).
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change from baseline to 24 months (Primary Outcome):
• T&E = +4.0 (SD 17.8)
• PRN = +5.1 (SD 16.3)
• Difference = -1.169 (95% CI: -6.864 to 4.526)
Mean BCVA change from baseline to 12 months:
• T&E = +6.1 (SD 17.8)
• PRN = +10.4 (SD 12.4)
• Difference = -4.343 (95% CI: -9.455 to 0.769)
*Vision Maintaining
Gain of ≥15 Letters at 24 months:
• T&E = 20.3%
• PRN = 27.8% (p=0.299)
Loss of ≥15 Letters at 24 months:
• T&E = 10.1%
• PRN = 12.5% (p=0.659)
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Central Subfield Thickness (CST)
The mean CST change at 24 months:
• T&E = -180 (SD 165)µm
• PRN = -247 (SD 230)µm
• Difference = +67 µm (p = 0.135)
*The mean CST change at 12 months:
• T&E = -168 (SD 229)µm
• PRN = -257 (SD 211)µm
• Difference = +89 µm (p = 0.049)
Safety
Patients with AEs
• T&E: 55 (79.7%)
• PRN: 50 (69.4%)
Patients with ocular-related AEs
Vitreous hemorrhage:
• T&E = 2
• PRN = 1
Macular hole:
• T&E = 1
• PRN = 0
Patients with non-ocular serious AEs
T&E = 4 (6%) and PRN = 3 (4%)
Cerebral infarction:
• T&E = 0
• PRN = 1
Tumor operations:
• T&E = 1
• PRN = 1
Infectious diseases:
• T&E = 2
• PRN = 0
Other surgeries:
• T&E = 1
• PRN = 0
Death from any cause:
• T&E = 0
• PRN = 1 (car accident).
Conclusion
The T&E regimen did not demonstrate non-inferiority to the PRN regimen in terms of BCVA improvement at 24 months. While T&E required fewer visits, PRN required fewer injections. These findings suggest that PRN may be more effective for long-term BCVA maintenance.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: “The BCVA assessors and the imaging technicians were masked to regimens allocation.” However, there are no details on the method of randomization and allocation concealment. The patient characteristics were well balanced between study arms (Table 1, all comparison p>0.05)
Missing Outcome Data
Low risk
Note: *The evidence that the result was not biased by missing outcome data: eTable 3 supplied the per-protocol analysis results as the sensitivity analysis.
Selection of the Reported Results
Low risk Note: Registration with the protocol
Deviations from Intended Observations
Some concerns Note: “The BCVA assessors and the imaging technicians were masked to regimens allocation”, but the patients were impossible to be masked. There is no information on whether the deviations from the intended intervention were balanced between groups. “Primary analyses were performed based on… intention-to-treat (ITT) principle.”
Measurement of the Outcome
Some concerns Note: “The BCVA assessors and the imaging technicians were masked …” However, this is a multiple–site clinical trial and measurement diversity may exist among various sites.
Overall
High risk
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