Topouzis F, Melamed S, Danesh-Meyer H, Wells A P, Kozobolis V, Wieland H, Andrew R, Wells D
II Department of Ophthalmology, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Periferiaki Odos Thessalonikis, Thessaloniki 56403, Greece.
Eur J Ophthalmol. 2007 Mar-Apr;17(2):183-90. doi: 10.1177/112067210701700206.
The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH).
This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were > or =24 mmHg at 9 AM and > or =21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12.
Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant.
Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH.
本研究的目的是比较0.004%曲伏前列素/0.5%噻吗洛尔滴眼液（Trav/Tim）与0.005%拉坦前列素/0.5%噻吗洛尔滴眼液（Lat/Tim）在开角型青光眼（OAG）或高眼压症（OH）患者中，每日早晨给药一次时降低眼压（IOP）的疗效和安全性。
这是一项在41个地点进行的随机、双盲、多中心、平行组、活性对照研究。在符合入选标准的访视中，如果患者符合纳入/排除标准，且符合条件的眼睛在上午9点的平均眼压值≥24 mmHg，在上午11点和下午4点的平均眼压值≥21 mmHg，则将患者随机（1:1）分配至指定的盲法用药组。如果任一眼睛的平均眼压>36 mmHg，则将患者排除。患者被指示每天上午9点使用指定的药物。在研究的治疗阶段，在第2周、第6周、第3个月和第9个月的上午9点测量眼压。在第6个月和第12个月的访视中，在上午9点、上午11点和下午4点测量眼压。统计方法包括重复测量方差分析（ANOVA）；为检验非劣效性，根据第12个月各时间点的ANOVA结果构建治疗组差异的95%置信区间。
41个地点招募了408例OAG或OH患者。1例患者在接受药物治疗前退出，因此Trav/Tim组207例和Lat/Tim组200例可进行安全性评估。两组的基线人口统计学特征以及眼压值无统计学差异。Trav/Tim组的平均眼压值低于Lat/Tim组，在第2周上午9点（p = 0.0081）、第6个月上午9点（p = 0.0056）、第6个月上午11点（p = 0.0128）时间点以及所有访视的上午9点时间点（p = 0.0235）具有统计学意义，此时Trav/Tim组的平均眼压低0.6 mmHg。两组与治疗相关的不良事件均较轻。尽管Trav/Tim组报告有充血的患者比例较高，但两组平均充血评分的差异不被认为具有临床相关性。
0.004%曲伏前列素/0.5%噻吗洛尔滴眼液产生的平均眼压水平在统计学上不劣于0.005%拉坦前列素/0.5%噻吗洛尔滴眼液。此外，在给药24小时后的上午9点，所有访视中0.004%曲伏前列素/0.5%噻吗洛尔的眼压在统计学上较低。0.004%曲伏前列素/0.5%固定复方滴眼液是降低眼压的有效治疗方法，对OAG或OH患者安全且耐受性良好。
