RESUMO
BACKGROUND: Eye drops containing 0.1% hyaluronic acid (HA) and 0.5% carboxymethylcellulose (CMC) applied one drop three times a day per affected eye were compared in patients with moderate keratitis or keratoconjunctivitis related to dry eye disease (DED). PATIENTS AND METHODS: This was a prospective, randomized, multicenter, Phase IIIB noninferiority study, with a single-masked phase in parallel mode with two groups over 84 days. The primary efficacy outcome was change in ocular surface (OS) staining between day 0 (D0) and day 35 (D35). The conjunctiva and cornea were stained with lissamine green and fluorescein. Secondary efficacy measures at day 84 (D84) were OS-staining score (SS), ocular comfort index, tear-film breakup time and how patients and investigators rated treatment efficacy and safety. RESULTS: At D35, 0.1% HA achieved a 46.6% reduction in OS-SS (-2.03±1.35 points, n=39 patients) and 0.5% CMC treatment, followed by a 34.9% reduction (-1.61±1.69 points, n=38 patients) compared to D0. At D84, the SS difference to D0 improved by -2.58±1.45 points (-59.2%) for 0.1% HA and -2.59±2.27 points (-54.4%) for 0.5% CMC. Ocular comfort-index scores improved, with significantly lower (better) values for stinging and itching on D84 for 0.1% HA. Patients assessed treatment with 0.1% HA as significantly better than 0.5% CMC (Likert scale, 4.82 vs 3.97; P=0.018). Four adverse events (AEs) occurred in four of 41 patients (9.8%) treated with 0.1% HA, and three AEs in two of 39 patients (5.1%) treated with 0.5% CMC. No serious AEs were noted. CONCLUSION: DED signs and symptoms of DED significantly improved with both eye drops. OS staining improved >54% at D84. Treatment was well tolerated, with only minor AEs <10%. 0.1% HA and 0.5% CMC were equally safe and effective. Significant and nonsignificant results were constantly in favor of 0.1% HA.
RESUMO
PURPOSE: Comparison of efficacy and safety of 0.2% and 0.18% hyaluronic acid (HA) eye drops three times a day (tid) in patients with moderate to severe dry eye disease, related to keratitis or keratoconjunctivitis. PATIENTS AND METHODS: Prospective, multicenter, randomized, single-masked, phase IIIb, noninferiority study (0.2% HA vs 0.18% HA) in two parallel groups over a period of 84 days. N=70 patients were evaluated. Primary efficacy outcome was ocular surface (OS) staining change on day 35 (D35), compared to baseline. Fluorescein and lissamine green were used for staining of cornea and conjunctiva. Secondary efficacy outcome included tear film breakup time, OS staining score on day 84 (D84), ocular comfort index, as well as patients' and doctors' evaluation. RESULTS: Compared to day 0 (D0), 0.2% HA achieved a 47.7% reduction in staining score (-3.00±2.81 [standard deviation] points, n=38 patients) at D35; 0.18% HA showed a 41.2% reduction (-2.59±2.20 [standard deviation] points, n=32 patients). Statistical analysis showed noninferiority in efficacy of 0.2% HA compared to 0.18% HA on D35. At D84, the reduction in staining score had further increased to 64.5% for 0.2% HA and to 56.4% for 0.18% HA. Both eye drops improved tear film breakup time and ocular comfort index values. Investigators and patients assessed both treatments with 5 of 7 points (Likert Scale, medians). The rate of adverse events (AE) was 2.3% for 0.2% HA and 7.1% for 0.18% HA with no serious AE. CONCLUSION: 0.2% and 0.18% HA eye drops significantly improved signs and symptoms of dry eye disease and were well tolerated with few AEs. Noninferiority of 0.2% HA compared to 0.18% HA was demonstrated for reduction of OS lesions. In some parameters, there was a nonsignificant trend in favor of 0.2% HA concentration.
RESUMO
BACKGROUND: Medical management of GERD mainly uses proton pump inhibitors. Alginates also have proven efficacy. The aim of this trial was to compare short-term efficacy of an alginate (Gaviscon®, 4 × 10 mL/day) and omeprazole (20 mg/day) on GERD symptoms in general practice. METHODS: A 14-day multicentre randomised double-blind double-dummy non-inferiority trial compared Gaviscon® (4 × 10 mL/day) and omeprazole (20 mg/day) in patients with 2-6 day heartburn episodes weekly without alarm signals. The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing. Secondary outcomes were the proportion of patients without heartburn by D7, pain relief by D7, and reduction in pain intensity by D7 and D14. RESULTS: 278 patients were recruited; 120 were included in the Gaviscon® group and 121 in the omeprazole group for the per protocol non-inferiority analysis. The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 (± 2.2) days for Gaviscon® and 2.0 (± 2.3) days for omeprazole (p = 0.93); mean intergroup difference was 0.01 ± 1.55 days (95% CI = -0.41 to 0.43): i.e., less than the lower limit of the 95% CI of -0.5 days predetermined to demonstrate non-inferiority. The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group: 3.7 ± 2.3 days vs. 3.1 ± 2.1 (p = 0.02). On D7, overall quality of pain relief was slightly in favour of omeprazole (p = 0.049). There was no significant difference in the reduction in pain intensity between groups by D7 (p = 0.11) or D14 (p = 0.08). Tolerance and safety were good and comparable in both groups. CONCLUSION: Gaviscon® was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn, and is a relevant effective alternative treatment in moderate GERD in primary care. TRIAL REGISTRATION: ISRCTN62203233.
