Long-term Suppressive Valacyclovir Treatment for Herpes Zoster Ophthalmicus

项目概要： 带状疱疹眼病研究（ZEDS）的目的是确定是否延长 口服伐昔洛韦抑制性抗病毒治疗可减少带状疱疹并发症 眼科（HZO），从而改善这一常见和潜在的视力的临床结果- 和危及生命的疾病。每年有1，000，000例带状疱疹（HZ）新发病例， 美国，10-20%为HZO。HZ和HZO的人口统计数据在加拿大相似， 美国，除了接种带状疱疹疫苗的保险要少得多 在加拿大的覆盖和使用。这项双盲、安慰剂对照研究的第一个目的是 一项多中心随机临床试验将检验抑制性抗病毒治疗 口服伐昔洛韦1000毫克，每日12个月，可降低新发或恶化的发生率 树枝状上皮角膜炎、基质角膜炎、内皮角膜炎或葡萄膜炎， 安慰剂组，12个月作为主要终点，18个月包括6个月随访- 治疗后，作为次要终点，在HZO患者中， 在入组前一年内出现这些疾病表现之一。第二个目标是 检验口服伐昔洛韦1000 mg抑制治疗12个月的假设 与安慰剂相比，每日可降低带状疱疹后神经痛（PHN）的严重程度和持续时间， 在相似的HZO患者中，12个月和18个月作为次要终点。PHN是一个 使人衰弱的慢性疼痛综合征，对生活质量产生负面影响，尤其是老年人 患者该研究将招募年龄在18岁及以上的免疫功能正常的患者， HZO在过去的不同时间被诊断，这些类型的活动性眼前节眼 去年的一年里，疾病。 符合条件的患者将以1：1的比例随机接受长期抑制治疗， 伐昔洛韦1000 mg/d或安慰剂，持续12个月，加上常规眼科护理，并随访 每3个月进行一次，共18个月，以确定新发或恶化的树枝状 上皮性角膜炎、基质性角膜炎、内皮性角膜炎或葡萄膜炎和/或 治疗12个月期间和治疗停止后6个月的PHN。的 关于PHN的结果可适用于其它位置的HZ。如果抑制 伐昔洛韦治疗被确定是有效的，潜在的破坏性疾病负担 的HZO和HZ可能会减少病人，以及每年的社会成本，估计在 美国是10亿美元。

PROJECT SUMMARY: The objective of the Zoster Eye Disease Study (ZEDS) is to determine whether prolonged suppressive oral antiviral treatment with valacyclovir reduces complications of Herpes Zoster Ophthalmicus (HZO), thereby improving clinical outcomes in this common and potentially vision- and life-threatening disease. There are 1,000,000 new cases of Herpes Zoster (HZ) per year in the USA, with 10-20% being HZO. The demographics of HZ and HZO are similar in Canada and the US, with the exception that vaccination against zoster has substantially less insurance coverage and usage in Canada. The first aim of this double-masked, placebo controlled multicenter randomized clinical trial will test the hypothesis that suppressive antiviral treatment for 12 months with oral valacyclovir 1000 mg daily reduces the rate of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or uveitis compared to placebo, at 12 months as the primary endpoint, and at 18 months including 6 months of follow- up after treatment, as the secondary endpoint, in patients with HZO who have had an episode of one of these disease manifestations during the year prior to enrollment. The second aim is to test the hypothesis that suppressive treatment for 12 months with oral valacyclovir 1000 mg daily reduces the severity and duration of postherpetic neuralgia (PHN), compared to placebo, at 12 months and at 18 months as secondary endpoints, in similar patients with HZO. PHN is a debilitating chronic pain syndrome that negatively impacts quality of life, especially in elderly patients. The study will enroll immunocompetent patients age 18 years and older who have HZO diagnosed at variable times in the past, with these types of active anterior segment ocular segment disease within the past year. Eligible patients will be randomized in a 1:1 ratio to long-term suppressive treatment with oral valacyclovir 1000 mg daily or placebo for 12 months, plus usual ophthalmic care, and followed every 3 months for a total of 18 months, to determine outcomes of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or uveitis and/or severity and duration of PHN during 12 months of treatment and for 6 months following treatment discontinuation. The results with regard to PHN may be applicable to HZ in other locations. If suppressive valacyclovir treatment is determined to be effective, the potentially devastating disease burden of HZO and HZ may be reduced for patients, as well as the annual costs to society, estimated in the USA to be one billion dollars.