Parasitic Ulcer Treatment Trial

寄生虫性溃疡治疗试验

• 批准号: 10626567
• 负责人: Jeremy David Keenan
• 金额: $ 156.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626567
• 关键词: Acanthamoeba; Acanthamoeba Keratitis; Adrenal Cortex Hormones; Advocate; Affect; Amoeba genus; Anti-Inflammatory Agents; Bacteria; Biological; Brazil; Clinical; Clinical Research; Collaborations; Contact Lenses; Cornea; Cyst; Data; Development; Diagnosis; Disease Outbreaks; Eligibility Determination; Enrollment; Equipoise; Eye; Eye Infections; Eyedrops; Fright; Gene Expression; Gene Expression Profile; Genes; Growth; Image; Immunologic Factors; In Vitro; India; Infection; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Integration Host Factors; Interleukin Gene; Intervention Trial; Keratoplasty; Knowledge; Masks; Metagenomics; Natural Immunity; Observational Study; Ophthalmologist; Organism; Outcome; Pain; Participant; Pathway interactions; Patients; Perforation; Pharmaceutical Preparations; Placebos; Polymerase Chain Reaction; Process; Prospective Studies; Prospective cohort; Provider; Quality of life; Randomized; Randomized, Controlled Trials; Recurrence; Regimen; Research Design; Research Personnel; Resolution; Risk; Risk Factors; Safety; Sample Size; Scleritis; Specialist; Specific qualifier value; Steroid therapy; Steroids; Swab; TLR4 gene; TLR8 gene; Techniques; Therapeutic; Thinness; Time; Topical Corticosteroids; Ulcer; United Kingdom; United States; Virulence Factors; Vision; Visual; Visual Acuity; Work; anterior chamber; clinical practice; clinical predictors; corneal scar; deep sequencing; endosymbiont; evidence base; genetic information; genetic predictors; improved; metagenomic sequencing; ocular pain; pathogen; polyhexamethylene biguanide; prednisolone; primary outcome; randomized trial; response; secondary analysis; secondary outcome; sodium phosphate; standard of care; topical antiseptic; transcriptome; treatment trial; trial design

PROJECT SUMMARY Introduction. Acanthamoeba keratitis is a blinding corneal infection with few treatment options. Corticosteroids are currently used by many cornea specialists for acanthamoeba keratitis, but their use is controversial given their ability to promote acanthamoeba growth. Trial Design. This proposed study is a randomized trial assessing whether topical corticosteroids improve clinical and visual outcomes. • Inclusion. 200 patients with microbiologic evidence of acanthamoeba keratitis (i.e., on culture, smear, or polymerase chain reaction) from 11 centers in the United States, United Kingdom, Brazil, and India will be eligible if there is evidence of ocular inflammation after 4 weeks of anti-amoebic therapy. • Pre-trial intervention. All participants will be treated with a standard of care anti-amoebic treatment, with the preferred treatment being polyhexamethylene biguanide (PHMB) 0.02% eyedrops. • Trial intervention. After the fourth week of anti-amoebic treatment, if there is ocular inflammation (i.e., corneal, episcleral, or anterior chamber inflammation) then participants will be offered enrollment and randomized to either topical prednisolone sodium phosphate 1% or placebo eyedrops. Participants will continue PHMB therapy while on the study medications. • Trial outcomes. The primary outcome is best corrected visual acuity with a hard contact lens, assessed at months 6 and 7. Secondary outcomes include (i) time to clinical resolution, (ii) time to perforation or therapeutic corneal transplantation, (iii) corneal thinning, (iv) eye pain, and (v) quality of life. Secondary objectives. Corneal swabs will be collected at the time of the initial diagnosis and processed with metagenomic deep sequencing to determine if endosymbiotic bacteria living within the amoeba, or the organism’s gene expression profile, is predictive of severe inflammation. Conjunctival swabs will be collected prior to randomization to determine if the host gene expression profile is predictive of severe inflammation. Impact. The trial will provide much-needed evidence using the highest-quality study design: a randomized controlled trial. Moreover, this will be the largest prospective cohort of acanthamoeba keratitis to date, with extensive microbiological, clinical, and imaging data from enrollment centers on 4 continents, which will allow numerous secondary analyses. The study results will be directly useful for providers who treat acanthamoeba keratitis as well as the patients currently affected by this blinding infection.

项目摘要 介绍。阿斯塔莫巴角膜炎是一种盲目的角膜感染，几乎没有治疗选择。皮质类固醇 目前已被许多角膜专家用于acanthamoeba角膜炎，但它们的使用有争议 他们促进阿斯塔梅巴增长的能力。 试用设计。这项提出的研究是一项随机试验评估，局部皮质类固醇是否有所改善 临床和视觉结果。 •包容。 200例具有acanthamoeba角膜炎的微生物学证据的患者（即培养，涂片， 来自美国，英国，巴西和印度的11个中心的聚合酶链反应） 如果有4周的抗AMOEBIC治疗后有眼部炎症的证据，将符合条件。 •预审干预。所有参与者将通过护理标准的抗氨比治疗进行治疗， 首选的治疗是聚甲基甲基二圭亚奈德（PHMB）0.02％眼架。 •试用干预。在抗Amoebic治疗的第四周之后，如果发生眼部炎症（即 角膜，院子或前室炎症）然后将提供参与者的入学人数 随机分配给局部泼尼松龙磷酸钠1％或安慰剂眼睛。参与者会 在研究药物中继续使用PHMB治疗。 •试验结果。主要结果是用硬透镜最好校正视力， 在第6和第7个月进行评估。次要结果包括（i）临床分辨率的时间，（ii） 穿孔或治疗性角膜移植，（iii）角膜稀疏，（iv）眼痛和（v）质量 生活。 次要目标。最初诊断时将收集角膜拭子 宏基因组深度测序，以确定居住在变形虫中的内体细菌还是 有机体的基因表达谱是预测严重感染的。将收集结膜棉签 在随机化之前，以确定宿主基因表达谱是否可以预测严重的炎症。 影响。该试验将使用最高质量的研究设计提供急需的证据： 对照试验。此外，这将是迄今为止最大的acanthamoeba角膜炎队列，迄今为止 来自四大洲的入学中心的广泛的微生物，临床和成像数据，这将允许 许多次要分析。研究结果将直接对治疗Acanthamoeba的提供商有用 角膜炎以及目前受这种失明感染影响的患者。