The Effect of the Oral PKC β Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies
The Effect of the Oral PKC β Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies
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DOI：
10.1167/iovs.12-11055
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Berg, Paul H.
中科院分区：
文献类型：
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作者：
Sheetz, Matthew J.;Aiello, Lloyd Paul;Berg, Paul H.
目的。通过对两项 3 期试验（MBDL 和 MBCU）进行前瞻性定义的联合分析，评估 ruboxistaurin (RBX) 对视力丧失的影响。这两项为期 3 年的随机、安慰剂对照、双盲试验中的患者均具有最佳矫正早期治疗糖尿病视网膜病变研究 (ETDRS) 视力 (VA) >= 75 个字母（类似于 20/32 Snellen），ETDRS 视网膜病变级别为 20 至 47D (MBDL) 或 35B 至 53E (MBCU)，且之前未接受过全视网膜或局部光凝治疗。至少一只眼睛处于基线。患者接受口服安慰剂（两项研究中总共 N = 508 名）或 RBX 32 mg/d（总共 N = 520 名）。最佳校正 ETDRS VA 在 3 年 (MBDL) 或 18 至 48 个月 (MBCU) 中以 6 个月为间隔进行测量。持续中度视力丧失 (SMVL) 定义为患者参与研究的最后 6 个月内 VA 较基线下降 15 个字母或更多。 结果。在合并研究中（总共 N = 1028），安慰剂组中 4.4% 的患者发生 SMVL，而 RBX 治疗组中这一比例为 2.3% (P - 0.069)。在至少 2 年随访的患者中（总共 N = 825 名），RBX 组的 SMVL 较低（安慰剂组为 4.4%，RBX 组为 2.1%，P = 0.045）。其他 VA 相关测量（平均 VA、对比敏感度、视觉功能问卷 25 [VFQ-25]）要么倾向于 RBX 受益，要么在统计上也显着有利于 RBX。相比之下，糖尿病性黄斑水肿 (DME) 形态相关测量（黄斑受累中心的出现情况、光学相干断层扫描 [OCT] 确定的黄斑中心厚度、局灶光凝术的应用）并未显示出支持或反对 RBX 的一致趋势。这两项 3 期试验的前瞻性联合分析中的 SMVL 数据表明，RBX 对视力丧失的影响程度与之前两项研究中所见的效果相似（比标准治疗减少约 50%）。然而，事件发生率较低且未达到统计学显着性。 （ClinicalTrials.gov 编号、NCT00133952、NCT00090519。）（Invest Ophthalmol Vis Sci. 2013；54：17501757）DOI：10.1167/iovs.12-11055
PURPOSE. To assess the effect of ruboxistaurin (RBX) on vision loss through a prospectively defined combined analysis of two phase 3 trials (MBDL and MBCU).METHODS. Patients in both of these 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) >= 75 letters (similar to 20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total). Best-corrected ETDRS VA was measured at 6-month intervals for 3 years (MBDL) or for 18 to 48 months (MBCU). Sustained moderate visual loss (SMVL) was defined as a 15-letter or more reduction from baseline in VA sustained for a patient's last 6 months of study participation.RESULTS. In the combined studies (N = 1028 total), SMVL occurred in 4.4% of placebo-versus 2.3% of RBX-treated patients (P - 0.069). In patients with a minimum of 2 years of follow-up (N = 825 total), there was less SMVL in the RBX group (4.4% placebo versus 2.1% RBX, P = 0.045). Other VA-related measures (mean VA, contrast sensitivity, Visual Functioning Questionnaire 25 [VFQ-25]) either trended toward a benefit for RBX or were also statistically significant in favor of RBX. In contrast, diabetic macular edema (DME) morphology-related measures (occurrence of significant center of macula involvement, optical coherence tomography [OCT]-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX.CONCLUSIONS. SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a magnitude of effect of RBX on vision loss similar to that seen in two prior studies (approximately 50% reduction above standard care). However, event rates were low and statistical significance was not achieved. (ClinicalTrials.gov numbers, NCT00133952, NCT00090519.) (Invest Ophthalmol Vis Sci. 2013;54:17501757) DOI:10.1167/iovs.12-11055