Planning Grant for Parasitic Ulcer Treatment Trial

描述(由申请人提供)：这项研究的目标是计划一项临床试验，以确定更好的诊断和治疗棘阿米巴角膜炎的方法。棘阿米巴角膜炎是一种致盲的角膜感染，在美国是越来越常见的视力障碍原因。棘阿米巴角膜炎可能很难诊断，因为临床症状没有特异性，而且即使存在感染，培养也可能是阴性的。理想的治疗方案尚不清楚。大多数角膜专家使用多种外用和口服药物进行治疗。然而，多种药物并不一定比单一药物更有效，而且联合使用也存在角膜毒性和粘附性差的缺点。使用局部皮质类固醇治疗棘阿米巴角膜炎是有争议的。一些角膜专家反对使用皮质类固醇，因为它们被证明可以促进棘阿米巴的增殖。其他人则使用皮质类固醇作为辅助治疗，以减少炎症和疼痛。在这项研究中，我们希望通过以下具体目的来改善棘阿米巴角膜炎的诊断和治疗的证据基础：1)确定几种棘阿米巴角膜炎诊断试验的敏感性和特异性，包括临床检查， 培养、涂片、聚合酶链式反应和共聚焦显微镜。2)确定单药外用洗必泰治疗棘阿米巴角膜炎患者的微生物治愈时间是否与外用洗必泰、丙烷胺加口服伏立康唑多药治疗患者的微生物治愈时间相似。3)确定随机使用外用皮质类固醇治疗棘阿米巴角膜炎的患者是否会比随机使用安慰剂的患者视力更好。传统上，棘阿米巴的大规模临床研究被证明是困难的，因为尽管棘阿米巴角膜炎的风险对隐形眼镜佩戴者来说意义重大，但在任何一个中心都存在相对较少的病例。我们通过在三个中心之间建立合作来解决这个问题：加州大学旧金山分校、伊利诺伊大学芝加哥分校和印度的阿拉文德眼科医院。因此，这项拟议的研究将构成有史以来最大的关于棘阿米巴角膜炎的前瞻性随机研究，也只是第二个随机临床试验。在计划期间，我们建议敲定研究方案和统计分析计划，并开始招募研究对象，以评估招生潜力。

DESCRIPTION (provided by applicant): The objective of this study is to plan for a clinical trial to determine better ways to diagnose and treat acanthamoeba keratitis. Acanthamoeba keratitis is a blinding corneal infection that is an increasingly common cause of visual impairment in the United States. Acanthamoeba keratitis can be difficult to diagnose, since clinical signs are nonspecific, and cultures can be negative even if infection is present. The ideal treatment regimen is not clear. Most corneal specialists treat with multiple topical and oral agents. However, multiple agents may not be more effective than a single agent, and the use of multiple agents has the disadvantages of corneal toxicity and worse adherence. The use of topical corticosteroids for acanthamoeba keratitis is controversial. Some cornea specialists oppose the use of corticosteroids, since they have been shown to promote acanthamoeba proliferation. Others have used corticosteroids as an adjunctive therapy to reduce inflammation and pain. In this study, we expect to improve the evidence base for the diagnosis and management of acanthamoeba keratitis, through the following specific aims: 1) To determine the sensitivity and specificity of several diagnostic tests for acanthamoeba keratitis, including clinical examination, culture, smear, PCR, and confocal microscopy. 2) To determine whether patients randomized to single agent therapy for acanthamoeba keratitis with topical chlorhexidine have similar microbial cure times compared to those randomized to multiple agent therapy with topical chlorhexidine and propamidine plus oral voriconazole 3) To determine whether patients being treated for acanthamoeba keratitis who are randomized to topical corticosteroids will have better vision compared to those randomized to a placebo. Large clinical studies for acanthamoeba have traditionally proven difficult, because while the risk of acanthamoeba keratitis is significan for contact lens wearers, relatively few cases present at any one center. We address this by establishing a collaboration between 3 centers: the University of California, San Francisco, the University of Illinois at Chicago, and the Aravind Eye Hospitals in India. As a result, the proposed study would make up the largest prospective randomized study on acanthamoeba keratitis ever performed, and only the second randomized clinical trial. During the course of the planning period, we propose to finalize the study protocol and statistical analysis plan, and to start recruiting study subjects in order to assess enrollment potential.