Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial
NCT02103738 | CANTREAT Trial | Kertes PJ et al. (2020)
Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmology, 2020; 138(3):244-250.
Locations
27 treatment centers in Canada
Study Period
May 2013 – August 2018
Study Design
Randomized, open-label, multicenter, noninferiority trial
Study Population
Experimental Group
Control Group
Follow-up Time: 229 (78.2%)
Outcomes
Durability
24 months
Vision
Number of Injections The mean number of ranibizumab injections over 24 months:
• T&E: 17.6 injections
• Monthly: 23.5 injections
• Difference: 5.9 injections (95% CI, 5.4 to 6.5; p < 0.001) Treatment Interval In the T&E arm:
• 73.7% (95% CI, 67.6%-79.3%) of the patients were able to extend their treatment interval to 8 or more weeks during the 24 months of treatment
• 43.1% (95% CI, 36.6%-49.8%) of patients reached the 12-week maximum extension interval
Other
N/A
Immunognicity
Not reported.
Pharmokinetics
Not reported.
Anatomic
Best-Corrected Visual Acuity (BCVA) The mean change in BCVA (ETDRS letters) at 24 months (primary outcome):
• T&E: +6.8 ± 14.1
• Monthly: +6.0 ± 12.6
• Difference: 0.9 letters (95% CI, -1.6 to 3.3); p = 0.21 Vision Maintaining The proportion of patients gaining ≥10 ETDRS letters:
• T&E: 42.9% (95% CI: 36.4% to 49.5%)
• Monthly: 36.4% (95% CI: 30.2% to 43.1%)
• Difference: 6.4% (-2.9% to 15.5%; p = 0.18) The proportion of patients gaining ≥15 ETDRS letters:
• T&E: 25.5% (95% CI: 20.1% to 31.7%)
• Monthly: 23.1% (95% CI: 17.8% to 29.2%)
• Difference: 2.4% (95% CI: -6.8% to 11.6%; p = 0.59) The proportion of patients losing ≥10 ETDRS letters:
• T&E: 9.5% (95%CI: 6.1% to 14.1%)
• Monthly: 9.8% (95% CI: 6.2% to 4.4%)
• Difference: 0.3% (-9.0% to 9.5%; p > 0.99) The proportion of patients losing ≥15 ETDRS letters:
• T&E: 6.5% (95%CI: 4.7% to 10.5%)
• Monthly: 5.8% (95% CI: 3.1% to 9.7%)
• Difference: -0.7% (95% CI, -9.9% to 8.5%); p = 0.85
Safety
AEs Not reported Study Discontinuation Patients discontinued the study:
• T&E: 17.1% (49/287)
• Monthly: 21.8% (64/293) Death
• T&E: 1.4% (6/287)
• Monthly: 2.7% (8/293)
Conclusion
The CANTREAT trial demonstrated that a Treat-and-Extend regimen with ranibizumab was not worse than monthly dosing in maintaining vision through 24 months while requiring significantly fewer injections.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: (from the protocol) “The randomization schedule was generated by the study biostatistician using a permuted-block design for each site separately so treatment arms are balanced within each site.” In addition, “baseline demographics and disease characteristics were similar between the treatment groups.”
Missing Outcome Data
Some concerns
Note: No evidence shows that the result was not biased by missing outcome data. According to Table 1, all discontinuation rates with reasons were balanced between the two groups. Therefore, it is unlikely that missingness in the outcome depended on its true value.
Selection of the Reported Results
Low risk Note: registration with protocol.
Deviations from Intended Observations
Some concerns Note: This is an open-label study. No information on whether deviations from the intended intervention arose because of the trial context. In addition, ITT was applied for analysis.
Measurement of the Outcome
Some concerns Note: As a multiple-center study, no information was supplied on the quality control of the measurement. There may be diversity in BCVA measurement between different sites.
Overall
High risk
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