Planning Grant for Parasitic Ulcer Treatment Trial

寄生虫性溃疡治疗试验规划拨款

基本信息

批准号：
8281382
负责人：
Jeremy David Keenan
金额：
$ 21.87万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8281382
关键词：
Acanthamoeba Acanthamoeba Keratitis Address Adherence Adrenal Cortex Hormones Advocate Biguanides California Case Series Characteristics Chicago Chlorhexidine Clinical Clinical Research Clinical Trials Collaborations Combined Modality Therapy Conduct Clinical Trials Confocal Microscopy Contact Lenses Cornea Cyst Diagnosis Diagnostic Diagnostic tests Disadvantaged Disease Disease Outbreaks Effectiveness Enrollment Evidence based treatment Eye Goals Gold Grant Growth Hospitals Illinois India Infection Inflammation Lead Local Anti-Infective Agents Methods Ophthalmologist Oral Outcome Pain Patients Pharmaceutical Preparations Phase Physicians Placebos Polymerase Chain Reaction Protocols documentation Randomized Randomized Clinical Trials Randomized Controlled Trials Recruitment Activity Recurrence Regimen Relative (related person)Research Risk Role San Francisco Sensitivity and Specificity Specialist Study Subject Testing Time Topical Corticosteroids Toxic effect Treatment Protocols Ulcer United States Universities Vision Visit Visual Acuity Visual impairment Voriconazole Work antimicrobial drug care systems evidence base improved microbial ocular pain pathogen polyhexamethylene biguanide prospective treatment trial trial comparing

项目摘要

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. PUBLIC HEALTH RELEVANCE: This research will provide evidence on best practices for the diagnosis and treatment of acanthamoeba keratitis. The trial will lead to an understanding of (1) the utility of diagnostic tests for acanthamoeba keratitis, (2) the effectiveness of monotherapy versus combination therapy for the treatment of acanthamoeba keratitis, and (3) the potential benefit of adding topical corticosteroids. We expect this trial to enhance patient outcomes by aiding physicians in the diagnosis and treatment of acanthamoeba keratitis.

描述（由申请人提供）：本研究的目的是计划一项临床试验，以确定诊断和治疗棘阿米巴角膜炎的更好方法。棘阿米巴角膜炎是一种致盲性角膜感染，在美国是导致视力障碍的越来越常见的原因。棘阿米巴角膜炎可能很难诊断，因为临床症状是非特异性的，即使存在感染，培养也可能呈阴性。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依从性较差的缺点。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，因为它们已被证明会促进棘阿米巴增殖。其他人则使用皮质类固醇作为辅助疗法来减轻炎症和疼痛。在这项研究中，我们希望通过以下具体目标来改善棘阿米巴角膜炎的诊断和治疗的证据基础：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的多药治疗的患者是否具有相似的微生物治愈时间 3) 确定接受棘阿米巴角膜炎治疗的患者是否具有相似的微生物治愈时间与随机接受安慰剂的患者相比，随机接受局部皮质类固醇治疗的患者视力会更好。传统上，针对棘阿米巴的大型临床研究被证明是困难的，因为虽然棘阿米巴角膜炎的风险对于隐形眼镜佩戴者来说是显着的，但在任何一个中心出现的病例相对较少。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阿拉文眼科医院。因此，拟议的研究将成为迄今为止针对棘阿米巴角膜炎进行的最大规模的前瞻性随机研究，也是第二项随机临床试验。在规划期间，我们建议最终确定研究方案和统计分析计划，并开始招募研究对象以评估入学潜力。公共卫生相关性：这项研究将为诊断和治疗棘阿米巴角膜炎的最佳实践提供证据。该试验将有助于了解（1）棘阿米巴角膜炎诊断测试的实用性，（2）单一疗法与联合疗法治疗棘阿米巴角膜炎的有效性，以及（3）添加外用皮质类固醇的潜在益处。我们希望这项试验能够帮助医生诊断和治疗棘阿米巴角膜炎，从而提高患者的治疗效果。