BACKGROUND: To determine the adjunctive 24-h efficacy obtained with brinzolamide/timolol, or brimonidine/timolol fixed combinations (FCs) in open-angle glaucoma patients insufficiently controlled on travoprost monotherapy.METHODS: Prospective, observer-masked, active controlled, crossover, comparison. Qualified primary open-angle or exfoliative glaucoma patients with a baseline intraocular pressure (IOP) >18 mm Hg at 10:00 on travoprost monotherapy were randomized for 3 months to either brinzolamide/timolol, or brimonidine/timolol FC therapy adjunct to travoprost. Patients were then crossed-over to the opposite therapy for another 3 months. At baseline and at the end of each treatment period, the patients underwent 24-h IOP monitoring.RESULTS: Fifty patients completed the study. The mean 24-h baseline IOP on travoprost monotherapy was 20.1 mm Hg [95% confidence interval (CI): 19.6, 20.7 mm Hg]. Both adjunctive FC therapies significantly reduced the IOP at each time point and for the mean 24-h IOP (P<0.001) compared with travoprost monotherapy. Brinzolamide/timolol FC provided a significantly lower mean 24-h IOP (17.2 mm Hg, 95% CI: 16.4, 17.9 mm Hg) than brimonidine/timolol FC (18.0 mm Hg, 95% CI: 17.3, 18.8 mm Hg) (P<0.001). For all the 3 timepoints between 18:00 and 02:00, the brinzolamide/timolol FC provided a significantly lower IOP than the brimonidine/timolol FC (P≤0.036). For the other 3 timepoints, no significant differences were detected.CONCLUSIONS: This study demonstrated that both FCs provide statistically and clinically significant incremental 24-h IOP lowering to travoprost monotherapy. The brinzolamide/timolol FC however achieves a better mean 24-h IOP control owing to the greater efficacy in late afternoon and during the night.