Parasitic Ulcer Treatment Trial

项目总结 导言。棘阿米巴角膜炎是一种致盲的角膜感染，治疗方案很少。皮质类固醇 目前被许多角膜专家用于治疗棘阿米巴角膜炎，但由于 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改善的随机试验。 临床和视觉结果。 ·包容性。200名有棘阿米巴角膜炎微生物证据的患者(即培养、涂片、 或聚合酶链式反应)来自美国、英国、巴西和印度的11个中心 如果在4周的抗阿米巴治疗后有眼部炎症的证据，将符合条件。 ·审前干预。所有参与者都将接受标准的抗阿米巴治疗， 首选的治疗方法是0.02%的聚六亚甲基双胍(PHMB)滴眼液。 ·审判干预。在抗阿米巴治疗的第四周之后，如果有眼部炎症(即， 角膜、巩膜上膜或前房炎症)，然后参与者将被提供登记和 随机分为外用1%强的松龙磷酸钠滴眼液或安慰剂滴眼液。参与者将 在服用研究药物的同时继续PHMB治疗。 ·试验结果。主要结果是使用硬性隐形眼镜的最佳矫正视力， 在6个月和7个月进行评估。次要结果包括(I)临床缓解时间，(Ii) 穿孔或治疗性角膜移植，(Iii)角膜变薄，(Iv)眼睛疼痛，和(V)质量 生活。 次要目标。角膜拭子将在最初诊断时收集并进行处理 元基因组深度测序以确定生活在阿米巴内的内共生细菌，还是 生物体的基因表达谱，预示着严重的炎症。将收集结膜拭子 在随机化之前，确定宿主基因表达谱是否预测严重炎症。 冲击力。该试验将使用最高质量的研究设计提供急需的证据：随机 对照试验。此外，这将是迄今为止最大的棘阿米巴角膜炎预期队列， 来自四大洲注册中心的大量微生物学、临床和成像数据，这将使 大量的二次分析。这项研究结果将直接对治疗棘阿米巴的提供者有用 以及目前受这种致盲感染影响的患者。

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.