The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole vs Placebo
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 5
- 主要终点
- Incidence of Perforation or Therapeutic Penetrating Keratoplasty
研究概览
简要总结
The purpose of this study is to determine if the addition of oral voriconazole to topical treatment regimens results in lower rates of perforation in severe fungal corneal ulcers.
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 of oral voriconazole in severe ulcers reduces the rate of perforations. 240 fungal corneal ulcers with baseline visual acuity worse than 6/120 presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive oral voriconazole plus topical voriconazole and topical natamycin, or oral placebo plus topical voriconazole and topical natamycin. The primary outcome is the rate of perforation over the three month follow-up period.
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 worse than 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
- •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)
- •Known liver disease, including hepatitis or cirrhosis (Child-Pugh A-C)
- •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 better than 6/120 (20/400) in the study eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA can be used for enrollment)
- •Currently on rifampin, rifabutin, ritonavir, long acting barbiturates, phenytoin, carbamazepine, or other drugs known to interact with voriconazole
- •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
Oral Voriconazole
干预措施: Voriconazole (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Perforation or Therapeutic Penetrating Keratoplasty
时间窗: 3 months from enrollment
Hazard ratio of perforation or therapeutic penetrating keratoplasty (TPK) comparing voriconazole to placebo
次要结局
- Best Spectacle-corrected logMAR Visual Acuity(3 months after enrollment)
- Size of Infiltrate/Scar(3 weeks after enrollment)
- Number of Adverse Events(3-months from enrollment)
- Size of Infiltrate/Scar - 3 Months(3 months after enrollment)
- Hazard Ratio for Re-epithelialization(Up to 21 days)
- Minimum Inhibitory Concentration of Isolates - Natamycin(7 days)
- Minimum Inhibitory Concentration of Isolates - Voriconazole(7 days)
- Best Spectacle-corrected logMAR Visual Acuity at 3-weeks(3 weeks after enrollment)
- Microbiological Cure at 7 Days(7 days)
研究者
Thomas M. Lietman
Professor in Residence
University of California, San Francisco