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.

项目概要 简介 棘阿米巴角膜炎是一种致盲性角膜感染，皮质类固醇的治疗选择很少。 目前许多角膜专家使用它来治疗棘阿米巴角膜炎，但鉴于其使用存在争议 它们促进棘阿米巴生长的能力。 试验设计。这项拟议的研究是一项评估局部皮质类固醇是否有所改善的随机试验。 临床和视觉结果。 • 纳入 200 名具有棘阿米巴角膜炎微生物学证据的患者（即通过培养、涂片、 或聚合酶链反应）来自美国、英国、巴西和印度的 11 个中心 如果抗阿米巴治疗 4 周后有眼部炎症证据，则符合资格。 • 试验前干预将接受标准的抗阿米巴治疗。 首选治疗方法是 0.02% 聚六亚甲基双胍 (PHMB) 滴眼液。 • 抗阿米巴治疗第四周后，如果出现眼部炎症（即， 角膜、巩膜外层或前房炎症）然后将被提供注册并 参与者将随机接受局部泼尼松龙磷酸钠或安慰剂滴眼液。 在服用研究药物的同时继续 PHMB 治疗。 • 试验结果是硬性隐形眼镜的最佳矫正视力。 在第 6 个月和第 7 个月进行评估。次要结果包括 (i) 达到临床缓解的时间，(ii) 达到临床缓解的时间 穿孔或治疗性角膜移植，(iii) 角膜变薄，(iv) 眼睛疼痛，以及 (v) 角膜质量 生活。 次要目标是在初次诊断时收集角膜拭子并进行处理。 宏基因组深度测序以确定内共生细菌是否生活在阿米巴体内，或者 生物体的基因表达谱可预测严重炎症。 在随机化之前确定宿主基因表达谱是否可以预测严重炎症。 该试验将使用最高质量的研究设计提供急需的证据：随机试验。 此外，这将是迄今为止最大的棘阿米巴角膜炎前瞻性队列。 来自四大洲登记中心的广泛微生物学、临床和影像数据，这将允许 大量的二次分析结果将直接对治疗棘阿米巴的提供者有用。 角膜炎以及目前受这种致盲感染影响的患者。