Therapeutic Exploratory Study of Comparing Natamycin and Voriconazole to Treat Fungal Corneal Ulcer
Information source: University of California, San Francisco
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fungal Keratitis
Intervention: Natamycin 5% (Drug); Voriconazole (Drug); Corneal de-epithelialization (Procedure)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: University of California, San Francisco Official(s) and/or principal investigator(s): Thomas M Lietman, MD, Principal Investigator, Affiliation: Proctor Foundation, University of California, San Francisco Nisha Acharya, MD MS, Principal Investigator, Affiliation: Proctor Foundation, University of California, San Francisco N V Prajna, MD, Study Director, Affiliation: Aravind Eye Hospital, India
Summary
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.
Clinical Details
Official title: Mycotic Ulcer Treatment Trial Therapeutic Exploratory Study
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Best Spectacle Corrected Visual Acuity (BSCVA) 3 Months After Enrollment, Adjusting for Enrollment BSCVA in a Multiple Linear Regression Model
Secondary outcome: Time to Resolution of Epithelial DefectSize of Infiltrate/Scar Post-treatment Was Analyzed in a Linear Regression Model Using Enrollment Infiltrate/Scar Size as a Covariate. Subgroup Analysis - Best Spectacle-corrected Visual Acuity Examined by Voriconazole and Natamycin Treatment Arms in Subgroups of Fungal Ulcers (Fusarium Spp and Aspergillus Spp). 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
Detailed description:
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.
Eligibility
Minimum age: 16 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Locations and Contacts
Aravind Eye Hospital, Madurai, Tamil Nadu, India
Aravind Eye Hospital, Pondicherry, Tamil Nadu, India
Additional Information
Starting date: November 2007
Last updated: November 18, 2013
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