局部用妥布霉素-地塞米松与地塞米松-新霉素-多粘菌素及新霉素-多粘菌素-短杆菌肽用于控制白内障手术后炎症的比较：一项多中心、前瞻性、三臂、随机、双盲、对照、平行组研究的结果

Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin-polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after cataract surgery: results of a multicenter, prospective, three-arm, randomized, double-masked, controlled, parallel-group study.

作者信息

Notivol Ricardo, Bertin Donata, Amin Dina, Whitling Anna, Kennedy Margaret, Cockrum Paul C

机构信息

Clinical Research Department, Alcon Cusí, SA, Barcelona, Spain.

出版信息

Clin Ther. 2004 Aug;26(8):1274-85. doi: 10.1016/s0149-2918(04)80113-9.

DOI:10.1016/s0149-2918(04)80113-9

PMID:15476908

Abstract

BACKGROUND

Intraocular inflammation is typically treated with a combination of anti-inflammatory and anti-infective drugs. Tobramycin-dexamethasone (TD) has not been associated with any serious adverse events, indicating good tolerability.

OBJECTIVE

The aims of this study were the following: (1) to demonstrate noninferiority of TD compared with dexamethasone-neomycin-polymyxin (DNP) in terms of anti-inflammatory efficacy, (2) to compare the anti-inflammatory efficacy of TD and DNP with that of a "placebo" control (antibiotic without anti-inflammatory agent), and (3) to provide additional safety data on TD.

METHODS

This prospective, double-masked, parallel-group study was conducted at 22 ophthalmology clinics across Europe and Brazil. Patients aged > 18 years undergoing cataract surgery were randomly assigned, in a 2:2:1 ratio, to receive tobramycin 3 mg/mL plus dexamethasone 1 mg/mL, dexamethasone 1 mg/mL plus neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 6000 IU/mL, or neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 7500 IU/mL plus gramicidin 20 microg/mL. All treatments were given as 1 drop instilled in the operated eye q.i.d. for 21 days. The primary efficacy end point, intraocular inflammation (determined using the sum of scores on anterior chamber cells and aqueous flare), was assessed at days 3, 8, 14, and 21 after surgery.

RESULTS

A total of 271 patients were enrolled (158 women, 113 men; age range 42-90 years) (TD, 104 patients; DNP, 110 patients; and neomycin-polymyxin-gramicidin [NPG], 57 patients). Intraocular inflammation was similar in the TD and DNP groups at all time points. At days 8, 14, and 21, inflammation scores were significantly lower with TD than with NPG (all, P < 0.05). At day 8, the inflammation score was significantly lower with DNP than with NPG (P < 0.05). A greater number of patients receiving NPG experienced treatment-related ocular allergic reactions compared with patients receiving TD (P < 0.05). One patient receiving TD (1.0%) and 5 given NPG (9.0%) were withdrawn due to ocular allergic reactions. None of the patients experienced an increase in intraocular pressure > or =10 mm Hg from baseline.

CONCLUSIONS

In this study of patients undergoing cataract surgery combination therapy with TD was noninferior to DNP and was well tolerated.

摘要

背景

眼内炎症通常采用抗炎和抗感染药物联合治疗。妥布霉素-地塞米松（TD）未出现任何严重不良事件，表明其耐受性良好。

目的

本研究的目的如下：（1）在抗炎疗效方面证明TD与地塞米松-新霉素-多粘菌素（DNP）相比不劣效；（2）将TD和DNP的抗炎疗效与“安慰剂”对照（不含抗炎剂的抗生素）进行比较；（3）提供关于TD的更多安全性数据。

方法

这项前瞻性、双盲、平行组研究在欧洲和巴西的22家眼科诊所进行。年龄>18岁且接受白内障手术的患者按2:2:1的比例随机分配，分别接受3 mg/mL妥布霉素加1 mg/mL地塞米松、1 mg/mL地塞米松加3500 IU/mL硫酸新霉素加6000 IU/mL硫酸多粘菌素B或3500 IU/mL硫酸新霉素加7500 IU/mL硫酸多粘菌素B加20 μg/mL短杆菌肽治疗。所有治疗均为每天4次，每次1滴，滴入手术眼，持续21天。在术后第3、8、14和21天评估主要疗效终点，即眼内炎症（使用前房细胞和房水闪光评分总和确定）。

结果

共纳入271例患者（158例女性，113例男性；年龄范围42 - 90岁）（TD组104例患者；DNP组110例患者；新霉素-多粘菌素-短杆菌肽[NPG]组57例患者）。TD组和DNP组在所有时间点的眼内炎症情况相似。在第8、14和21天，TD组的炎症评分显著低于NPG组（均P < 0.05）。在第8天，DNP组的炎症评分显著低于NPG组（P < 0.05）。与接受TD治疗的患者相比，接受NPG治疗的患者发生与治疗相关的眼部过敏反应的人数更多（P < 0.05）。1例接受TD治疗的患者（1.0%）和5例接受NPG治疗的患者（9.0%）因眼部过敏反应退出研究。所有患者的眼压均未较基线升高≥10 mmHg。