Mycotic Ulcer Treatment Trial Therapeutic Exploratory Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Best Spectacle Corrected Visual Acuity (BSCVA) 3 Months After Enrollment, Adjusting for Enrollment BSCVA in a Multiple Linear Regression Model
研究概览
简要总结
We evaluated whether voriconazole is a superior treatment to natamycin for filamentous fungal keratitis in a randomized, masked, controlled trial. This is a therapeutic exploratory study to investigate the safety and feasibility of conducting a larger study and to generate preliminary data.
详细描述
Fungal ulcers tend to have very poor outcomes with the most common treatments, amphotericin B and natamycin. There has been only a single randomized trial of anti-fungal therapy for fungal ulcers and no new medications have been approved by the FDA since the 1960s. There are studies that indicate that the newer triazoles, such as voriconazole, are more effective in vitro against filamentous fungi such as Aspergillus spp., a common cause of fungal keratitis1-3. Despite a number of case reports and in vitro studies, there has been no systematic attempt to determine whether it is more or less effective clinically than natamycin, the only commercially available FDA-approved agent. There is little data available for physicians to make an informed, evidence-based decision on choice of antifungal.
We evaluated whether voriconazole is a superior treatment to natamycin for filamentous fungal keratitis in a randomized, masked, controlled trial. This is a therapeutic exploratory study to investigate the safety and feasibility of conducting a larger study and to generate preliminary data. The primary outcome is visual acuity at 3 months from enrollment. A subset of patients will be followed at 4 years from enrollment.
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 KOH (or Giemsa or any other stain) or culture
- •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 in-patient or to be treated as an out-patient and come back every 48-72 hours to receive fresh medication for 3 weeks
- •Appropriate consent
排除标准
- •Overlying epithelial defect < 0.5 mm at its greatest width at presentation
- •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 (20/200) in the fellow eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA 6/60 or better qualifies 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
1
Topical voriconazole with corneal de-epithelialization
干预措施: Voriconazole (Drug)
1
Topical voriconazole with corneal de-epithelialization
干预措施: Corneal de-epithelialization (Procedure)
2
Topical voriconazole without corneal de-epithelialization
干预措施: Voriconazole (Drug)
3
Topical natamycin with corneal de-epithelialization
干预措施: Natamycin 5% (Drug)
3
Topical natamycin with corneal de-epithelialization
干预措施: Corneal de-epithelialization (Procedure)
4
Topical natamycin without corneal de-epithelialization
干预措施: Natamycin 5% (Drug)
结局指标
主要结局
Best Spectacle Corrected Visual Acuity (BSCVA) 3 Months After Enrollment, Adjusting for Enrollment BSCVA in a Multiple Linear Regression Model
时间窗: 3 months from enrollment
The primary efficacy endpoint was BSCVA at 3 months in the study eye, using a linear regression model with 3-month BSCVA measured in logMAR (logarithm of the Minimum Angle of Resolution) as the outcome variable and treatment arm (voriconazole vs natamycin) and enrollment logMAR BSCVA and corneal de-epithelialization (yes or no) as covariates.
次要结局
- Best Hard Contact Lens-corrected Visual Acuity 3 Months After Enrollment in a Multiple Linear Regression Model With Enrollment Hard Contact Lens-corrected Visual Acuity as a Covariate(3 months from enrollment)
- Time to Resolution of Epithelial Defect(3 months from enrollment)
- Size of Infiltrate/Scar Post-treatment Was Analyzed in a Linear Regression Model Using Enrollment Infiltrate/Scar Size as a Covariate.(3 months from enrollment)
- Subgroup Analysis - Best Spectacle-corrected Visual Acuity Examined by Voriconazole and Natamycin Treatment Arms in Subgroups of Fungal Ulcers (Fusarium Spp and Aspergillus Spp).(3 months from enrollment)