Crossover randomized multicentre clinical trial comparing the efficacy and tolerability of fixed-combinations of 0.1% brimonidine/0.5% timolol versus 1% dorzolamide/0.5% timolol as adjunctive therapies to prostaglandin analogues: Aibeta Crossover Study

Abstract

This multicentre, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed-combinations 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for eight weeks. These patients were then crossed over to the alternative treatment arm for another eight weeks. The intraocular pressure (IOP) reduction (primary outcome), adverse event occurrence, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patients’ interviews. BTFC instillation for eight weeks resulted in IOP reduction by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P <0.0001, mixed-effects model). Although adverse effects were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC instillation (P <0.0001). More patients preferred BTFC (P <0.0001) over DTFC, as the former caused minimal or no eye irritation. As BTFC offers better tolerability than DTFC with comparable IOP reduction, we recommend it as an alternative in patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.