Long-term Suppressive Valacyclovir Treatment for Herpes Zoster Ophthalmicus

项目总结： 带状疱疹眼病研究(ZEDS)的目标是确定 万乃洛韦抑制口服抗病毒治疗减少带状疱疹并发症 眼科(HZO)，从而改善这种常见的和潜在的视力的临床结果- 以及危及生命的疾病。年每年新增带状疱疹(HZ)病例100万例 美国，其中10%-20%是HZO。HZ和HZO的人口统计数据在加拿大和 美国，但带状疱疹疫苗的保险比美国少得多 在加拿大的覆盖范围和使用情况。这种双面罩安慰剂的第一个目的是 多中心随机临床试验将检验抑制性抗病毒治疗的假设 连续12个月口服万乃洛韦1000毫克可降低新发或恶化的速度。 树枝状上皮角膜炎、间质角膜炎、内皮角膜炎或葡萄膜炎与 安慰剂，以12个月为主要终点，18个月，包括6个月的随访 治疗后，作为次要终点，HZO患者发生 这些疾病的一种表现在入学前一年内。第二个目标是 口服万乃洛韦1000 mg抑制治疗12个月的假设检验 与安慰剂相比，每日减少带状疱疹后神经痛(PHN)的严重程度和持续时间， 12个月和18个月。PHN是一种衰弱的慢性疼痛综合征， 影响生活质量，尤其是老年患者。其他目标是评估 带状疱疹疫苗接种对研究结果的影响及新冠肺炎与冠状病毒感染的关系 19 HZO发病时的诊断和/或疫苗接种。 这项研究将招募患有HZO的18岁及以上具有免疫能力的患者 在过去的不同时期被诊断为活动性角膜炎和/或虹膜炎。 符合条件的患者将以1：1的比例随机分为长期口服抑制治疗组 万乃洛韦每日1000毫克或安慰剂，持续12个月，外加常规眼科护理，并 每3个月，共18个月，以确定新的或恶化的树突的结局 上皮性角膜炎、间质角膜炎、内皮角膜炎或葡萄膜炎和/或严重程度和持续时间 PHN在治疗12个月期间和治疗结束后6个月内。这个 有关PHN的结果可能适用于其他地区的HZ。如果压抑 万乃洛韦治疗被确定为有效，潜在的破坏性疾病负担 HZO和HZ的成本可能会减少，以及每年给社会带来的成本，估计在#年 美国将达到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 followup 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. PHN is a debilitating chronic pain syndrome that negatively impacts quality of life, especially in elderly patients. Additional aims are to evaluate the impact of vaccination against zoster on study outcomes and COVID-19, and relationship between COVID- 19 diagnosis and/or vaccination on onset of HZO. The study will enroll immunocompetent patients age 18 years and older who have HZO diagnosed at variable times in the past, with active keratitis and/or iritis 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.