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Updated: Jul 15, 2026
Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography
Published on: August 11, 2023
A randomized trial of Pegaptanib sodium for age-related macular degeneration used an innovative design to explore
Edward Mills1, Diane Heels-Ansdell, Steven Kelly
1Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. millsej@mcmaster.ca
Objective:
Effectively evaluating disease-modifying effects in clinical trials has posed a problem for clinical trialists and drug development. One method that has been proposed to evaluate disease-modifying effects has been the re-randomization of active group participants to discontinue the intervention after a period sufficient to produce therapeutic effects. We aimed to determine if this design would permit inferences regarding disease modification in a trial evaluating Pegaptanib sodium, an intra-ocular injection, for the treatment of age-related macular degeneration.
Study Design And Setting:
In two identically designed trials, 1,186 patients were randomized to receive 54 weeks of treatment. After 54 weeks, 1,053 were re-randomized to either stay on treatment or discontinue treatment. Patients were seen at multicenter outpatient clinics.
Results:
We found that patients randomized to discontinue treatment after 54 weeks of treatment and followed for a further 48 weeks, were significantly different than the control group (sham) in loss of 15 letters of vision (Relative Risk 0.70, 95% Confidence Interval 0.57-0.88, P=0.002), indicating that treatment is disease modifying. This effect was consistent throughout our sensitivity analyses.
Conclusion:
This trial is the first example of a clinical trial evaluating disease-modifying effects and this design should influence drug discovery to determine further therapeutic potential of pharmacologic interventions.
Insights
This study demonstrates that discontinuing Pegaptanib sodium treatment after 54 weeks significantly slowed vision loss in age-related macular degeneration patients. This re-randomization design effectively evaluates disease-modifying effects for future drug discovery.
Area of Science:
- Ophthalmology
- Clinical Trial Design
- Pharmacology
Background:
- Evaluating disease-modifying effects in clinical trials is challenging.
- Re-randomization of active treatment groups to discontinue therapy is a proposed method.
- Pegaptanib sodium is an intraocular injection for age-related macular degeneration (AMD).
Purpose of the Study:
- To assess if a re-randomization design can infer disease modification.
- To evaluate the disease-modifying potential of Pegaptanib sodium in AMD.
Main Methods:
- Two identical clinical trials were conducted with 1,186 patients randomized for 54 weeks.
- After 54 weeks, 1,053 patients were re-randomized to continue or discontinue Pegaptanib sodium treatment.
- Patients were monitored in multicenter outpatient clinics.
Main Results:
- Patients who discontinued treatment showed significantly less vision loss (15 letters) compared to the sham group (RR 0.70, P=0.002).
- This indicates Pegaptanib sodium has disease-modifying effects.
- Sensitivity analyses confirmed the consistency of these findings.
Conclusions:
- This trial successfully utilized a re-randomization design to demonstrate disease modification.
- The findings suggest Pegaptanib sodium has a disease-modifying effect in AMD.
- This trial design should inform future drug discovery for pharmacologic interventions.
