Comparisons of efficacy and safety between preserved and preservative-free brimonidine tartrate in glaucoma and ocular hypertension: a parallel-grouped, randomized trial

Abstract

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.

Figure 1

Flow chart of subject enrollment.

Figure 2

Proportions of patients surveyed regarding (A) the ease of opening the drug container and (B) the convenience of drug management. In both intention-to-treat (ITT) and per-protocol (PP) sets, significantly higher proportions of patients in the preserved-free group responded that it was very easy to open the drug container compared to preserved group (P < 0.001 for the ITT group, P = 0.002 for the PP group). In addition, a significantly higher proportion of patients in the preservative-free group reported that the drug container type caused no inconvenience for drug management (P = 0.002 for the ITT group and P = 0.005 for the PP group).