Planning Grant for Parasitic Ulcer Treatment Trial

描述（由申请人提供）：本研究的目的是计划进行临床试验，以确定诊断和治疗棘阿米巴角膜炎的更好方法。阿米巴角膜炎是一种致盲性角膜感染，在美国是一种越来越常见的视力损害原因。阿米巴角膜炎很难诊断，因为临床症状是非特异性的，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局部和口服药物进行治疗。然而，多种药物可能并不比单一药物更有效，并且使用多种药物具有角膜毒性和更差的粘附性的缺点。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，因为它们已被证明会促进棘阿米巴增殖。其他人使用皮质类固醇作为一种连续治疗，以减少炎症和疼痛。在这项研究中，我们期望通过以下具体目标来改善棘阿米巴角膜炎诊断和管理的证据基础：1）确定棘阿米巴角膜炎的几种诊断测试的敏感性和特异性，包括临床检查， 培养、涂片、PCR和共聚焦显微镜。 2)确定随机接受局部洗必泰单药治疗棘阿米巴角膜炎的患者与随机接受局部洗必泰和丙脒加口服伏立康唑多药治疗的患者相比是否具有相似的微生物治愈时间3）确定随机接受局部皮质类固醇治疗棘阿米巴角膜炎的患者与随机接受安慰剂治疗的患者相比是否具有更好的视力。 传统上证明棘阿米巴的大型临床研究是困难的，因为虽然棘阿米巴角膜炎的风险对于接触透镜配戴者是显著的，但在任何一个中心都存在相对较少的病例。我们通过建立3个中心之间的合作来解决这个问题：加州大学，旧金山弗朗西斯科，伊利诺伊大学芝加哥和印度的Aravind眼科医院。因此，拟议的研究将构成有史以来最大的棘阿米巴角膜炎前瞻性随机研究，只有第二个随机临床试验。在计划期间，我们建议最终确定研究方案和统计分析计划，并开始招募研究受试者，以评估入组潜力。

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.