Performance and Safety of a Sodium Hyaluronate Tear Substitute with Polyethylene Glycol in Dry Eye Disease: A Multicenter, Investigator-Masked, Randomized, Noninferiority Trial

Abstract

Purpose: To compare the performance and safety of 2 tear substitutes containing sodium hyaluronate (SH); one containing 0.15% SH and polyethylene glycol (PEG) 8000, and the other containing 0.18% SH. Methods: In this multicenter, randomized, investigator-masked, noninferiority trial, 83 patients with moderate or severe dry eye disease underwent a 2-week washout, and were then randomly assigned (1:1) to receive SH plus PEG tear substitute (n = 45) or comparator SH tear substitute (n = 38) 3-6 times daily for 3 months. The primary performance endpoint was the change from baseline in the ocular surface fluorescein staining (OSFS) score on day 28 in the per-protocol (PP) population, according to the 15-point Oxford Scheme, with a noninferiority margin of 2. Results: Both groups improved significantly in terms of signs and symptoms. Among the 78 patients without major protocol deviations (the PP population), the OSFS score decreased by 2.9 ± 2.0 on day 28 from 5.4 ± 1.3 at baseline in the SH plus PEG group and by 2.3 ± 2.2 from 5.2 ± 1.4 in the comparator group (95% confidence interval of the difference: -1.2 to 0.3), demonstrating noninferiority. On day 90, the improvement in OSFS scores was significantly greater in the SH plus PEG group (P = 0.0002). The safety profiles were satisfactory in both groups. Conclusion: SH plus PEG tear substitute was noninferior to SH tear substitute in the studied population and may provide additional benefits in the long term. ClinicalTrials.gov ID: NCT02975102.

Keywords: clinical study; dry eye; ocular lubricant; polyethylene glycol; sodium hyaluronate; tear substitute.

FIG. 1.

Patient flow diagram. C-SH, 0.18% sodium hyaluronate group; ITT, intention to treat; PP, per protocol; SH-PEG, 0.15% sodium hyaluronate-polyethylene glycol 8000 group.

FIG. 2.

Ocular surface fluorescein staining score (mean ±95% confidence interval) at each visit in the per-protocol population. C-SH, 0.18% sodium hyaluronate group; SH-PEG, 0.15% sodium hyaluronate-polyethylene glycol 8000 group. *P = 0.0002.

FIG. 3.

The global sum score of dry eye symptoms (mean ±95% confidence interval) in the per-protocol population. C-SH, 0.18% sodium hyaluronate group; SH-PEG, 0.15% sodium hyaluronate-polyethylene glycol 8000 group. *P = 0.0008; **P = 0.0026.

FIG. 4.

Quality of life assessments using the OSD-QoL^® questionnaire: change from baseline (day 0) on day 90 in the per-protocol population. C-SH, 0.18% sodium hyaluronate group; SH-PEG, 0.15% sodium hyaluronate-polyethylene glycol 8000 group; CFB, change from baseline; *P value ≤0.024.