Demographic information is presented in Table II . Of the total of 417 subjects randomised to one of the two treatment groups, 415 were evaluable for safety. Two patients were excluded because they did not receive study drug. Of these 415 patients, 401 were included in the ITT and 353 in the PP analyses. The distribution of evaluable patients in each of the two treatment arms is shown in Figure 1. The percentage of patients who discontinued the study was significantly greater (p < 0.001) in the Tobrex®/vehicle group (61/206; 30%) than in the TobraDex® group (23/211; 11%) [ Table III ]. There were 64 patients with major protocol deviations and all of their data, for all the visits, were excluded from the PP analysis ( Table IV ).
Schematic representation of patients included and excluded in the safety, intention-to-treat (ITT) and per-protocol (PP) populations. TobraDex® = tobramycin 3 mg/mL, dexamethasone 1 mg/mL; Tobrex®/vehicle = tobramycin 3 mg/mL/placebo.
A total of 168 (42%) out of 401 patients in the ITT analysis were men. The mean (± SD) age of the patients was 69.4 (± 10.7) years (range 25-91 years). The percentage of females in the TobraDex® group (52.7%) was significantly lower (p = 0.02) than in the Tobrex®/vehicle group (63.6%). The majority of patients (93%) were Caucasian. Treatment groups were comparable with regard to age, race and iris colour. The surgical technique used for cataract extraction, phacoemulsification, was the same for all enrolled patients. The site for the IOL implantation in 95% of the patients (396/417) was the capsular bag.
TobraDex® was significantly better (p < 0.05) than Tobrex®/vehicle in controlling post-cataract surgical inflammation at day 8 as shown by the percentage of patients with an inflammation score of zero (51% vs 21%) [Figure 2]. Differences were also significant (p < 0.05) at days 14 (76% vs 38%) and 21 (87% vs 55%). A trend (0.05 < p < 0.1) in favour of TobraDex® was observed at day 3 (14% vs 9%). The mean scores for inflammation by treatment and day are depicted in Figure 3. Similar results were obtained in the PP population. Subgroup analysis results examining efficacy of the treatments among sites indicated that TobraDex® was more effective than Tobrex®/vehicle in 21/22 sites.
Percentage of patients without anterior chamber inflammation (sum of cells and flares scores of zero) in the intent-to-treat data set. TobraDex® = tobramycin 3 mg/mL, dexamethasone 1 mg/mL; Tobrex®/vehicle = tobramycin 3 mg/mL/placebo. * p < 0.05; t 0.05 < p < 0.10.
Mean inflammation scores by treatment and day in the intent-to-treat data set. TobraDex® = tobramycin 3 mg/mL, dexamethasone 1 mg/mL; Tobrex®/vehicle = tobramycin 3 mg/mL/placebo. * p < 0.05.
With regard to secondary efficacy variables, TobraDex® was significantly better (p < 0.05) than Tobrex®/vehicle in cells, flare and physician's impression at days 3, 8, 14 and 21, as well as in controlling post-surgical ocular pain at days 1, 3, 8, 14 and 21 ( Table V ). The percentage of patients with ocular pain was significantly lower (p < 0.05) in the TobraDex® group at days 3, 8, 14 and 21 than in the Tobrex®/vehicle group (Figure 4). The percentage of patients with treatment failure was significantly greater (p < 0.001) in the Tobrex®/vehicle group (16%) than in the TobraDex® group (4%) [ Table III ].
Percentage of patients with ocular pain in the per-protocol data set. TobraDex® = tobramycin 3 mg/mL, dexamethasone 1 mg/mL; Tobrex®/vehicle = tobramycin 3 mg/mL/placebo. * p < 0.05.
In the population of 415 patients evaluable for safety, 112 patients (27%) reported a total of 155 adverse events (related and unrelated to the study medication). The distribution by assigned medication was 40 patients (19%) in the TobraDex® group with a total of 52 adverse events, and 72 patients (35%) in the Tobrex®/vehicle group, with a total of 103 adverse events, in particular hyperaemia (4.8%), corneal oedema (2.6%), increased fibrin (2.6%) and conjunctivitis (1.7%). Adverse events including ocular events related to treatment were generally mild to moderate and generally resolved without treatment. One patient receiving Tobrex®/vehicle discontinued the study due to a treatment-related adverse event (ocular allergic reaction). No deaths or serious adverse events related to treatment occurred. No patient experienced a clinically significant change in visual acuity or fundus parameters related to treatment. Clinically significant increases in IOP, defined as an IOP increase =10mm Hg, were reported in ten (4.7%) patients receiving TobraDex® and in two (1%) patients receiving Tobrex®/vehicle. These IOP increases were unrelated to treatment, were most commonly observed within 48 hours following surgery, and were attributed to the surgical procedure and viscoelastics used during the procedure. No patient had an IOP increase =10mm Hg related to treatment after the day of surgery.
Clin Drug Invest. 2004;24(9) © 2004 Adis Data Information BV
Cite this: Prophylactic Effectiveness of Tobramycin-Dexamethasone Eye Drops Compared with Tobramycin/Vehicle Eye Drops in Controlling Post-Surgical Inflammation in Cataract Patients - Medscape - Sep 01, 2004.