Mycotic Ulcer Treatment Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 323
- 试验地点
- 3
- 主要终点
- Best Spectacle-corrected logMAR Visual Acuity
研究概览
简要总结
The purpose of this study is to determine if natamycin or voriconazole results in better visual outcomes in fungal corneal ulcers, especially visual acuity.
详细描述
Fungal corneal ulcers tend to have very poor outcomes with commonly used treatments. There has only been a single randomized trial of anti-fungal therapy for mycotic keratitis, and no new ocular anti-fungal medications have been approved by the FDA since the 1960s. The triazole voriconazole has recently become the treatment of choice for systemic fungal infections such as pulmonary aspergillosis. The use of topical ophthalmic preparations of voriconazole has been described in numerous case reports, however there has been no systematic attempt to determine whether it is more or less clinically effective than natamycin. Additionally, there have been many case reports of the use of oral voriconazole in the treatment of fungal corneal ulcers, however there has been no systematic attempt to determine if it improves outcomes in severe ulcers.
This study is a randomized, double-masked, placebo-controlled trial to determine if the use natamycin or voriconazole results in better outcomes for fungal corneal ulcers. 368 fungal corneal ulcers with baseline visual acuity between 6/12 (20/40, logMAR 0.3) and 6/120 (20/400, logMAR 1.3) presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive either topical natamycin or topical voriconazole. The primary outcome is best spectacle-corrected logMAR visual acuity three months after enrollment, using best spectacle-corrected enrollment visual acuity as a co-variate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presence of a corneal ulcer at presentation
- •Evidence of filamentous fungus on smear (KOH wet mount, Giemsa, or Gram stain)
- •Visual acuity between 6/12 (20/40, logMAR 0.3) and 6/120 (20/400, logMAR 1.3)
- •The patient must be able to verbalize a basic understanding of the study after it is explained to the patient, as determined by physician examiner. This understanding must include a commitment to return for follow-up visits.
- •Willingness to be treated as an inpatient or to be treated as an outpatient and return every 3 days +/- 1 day until re-epithelialization and every week to receive fresh medication for 3 weeks
- •Appropriate consent
排除标准
- •Impending perforation
- •Evidence of bacteria on Gram stain at the time of enrollment
- •Evidence of acanthamoeba by stain
- •Evidence of herpetic keratitis by history or exam
- •Corneal scar not easily distinguishable from current ulcer
- •Age less than 16 years (before 16th birthday)
- •Bilateral ulcers
- •Previous penetrating keratoplasty in the affected eye
- •Pregnancy (by history or urine test) or breast feeding (by history)
- •Acuity worse than 6/60 (2/200) in the fellow eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA 6/60 or better qualifies for enrollment)
- •Acuity worse than 6/120 (20/400) or better than 6/12 (20/40) in the study eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA can be used for enrollment)
- •Known allergy to study medications (antifungal or preservative)
- •No light perception in the affected eye
- •Not willing to participate
研究组 & 干预措施
Topical Natamycin
干预措施: Natamycin (Drug)
Topical Voriconazole
干预措施: Voriconazole (Drug)
结局指标
主要结局
Best Spectacle-corrected logMAR Visual Acuity
时间窗: 3 months from enrollment
The primary analysis is best spectacle-corrected logMAR (logarithm of the Minimum Angle or Resolution) visual acuity, correcting for enrollment BSCVA and treatment arm in a multiple linear regression model. The pre-specified non-inferiority margin is less than 1.5 lines logMAR acuity. (Adjusted three-month visual acuity confidence bounds for the difference between the voriconazole and natamycin groups which meet or exceed 0.15 logMAR units would not permit noninferiority to be declared.) Note that this design also allows declaration of superiority (2-sided alpha of 0.05, corrected for an interim analysis).
次要结局
- Minimum Inhibitory Concentration of Isolates(3 months after enrollment)
- Microbiological Cure at 6 Days(7 days after enrollment)
- Best Spectacle-corrected logMAR Visual Acuity(3 weeks after enrollment)
- Hard Contact Lens-corrected Visual Acuity Measured in logMAR(3 months after enrollment)
- Size of Infiltrate/Scar(3 weeks and 3 months after enrollment)
- Time to Resolution of Epithelial Defect(From enrollment to the time of resolution of epithelial defect)
研究者
Thomas M. Lietman
Professor in Residence
University of California, San Francisco