Clinical trial NCT00557362: Therapeutic Exploratory Study of Comparing Natamycin and Voriconazole to Treat Fungal Corneal Ulcer
Official title: Mycotic Ulcer Treatment Trial Therapeutic Exploratory Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Fungal Keratitis
Keywords: Keratitis
Eye Infection, Fungal
Fungal Eye Infection
Ocular Infection, Fungal
Fungal Keratitis
Mycotic Infections, Ocular
Voriconazole
Natamycin
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: That Man May See, Inc.
name: Aravind Eye Hospitals, India
name: Dartmouth-Hitchcock Medical Center
First posted: 2007-11-14
Enrollment: 120
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Best Spectacle Corrected Visual Acuity (BSCVA) 3 Months After Enrollment, Adjusting for Enrollment BSCVA in a Multiple Linear Regression Model
timeFrame: 3 months from enrollment
Secondary outcomes:
measure: Time to Resolution of Epithelial Defect
timeFrame: 3 months from enrollment
measure: Size of Infiltrate/Scar Post-treatment Was Analyzed in a Linear Regression Model Using Enrollment Infiltrate/Scar Size as a Covariate.
timeFrame: 3 months from enrollment
measure: Subgroup Analysis - Best Spectacle-corrected Visual Acuity Examined by Voriconazole and Natamycin Treatment Arms in Subgroups of Fungal Ulcers (Fusarium Spp and Aspergillus Spp).
timeFrame: 3 months from enrollment
measure: 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
timeFrame: 3 months from enrollment
Other outcomes:
Locations:
city: Madurai
country: India
facility: Aravind Eye Hospital
state: Tamil Nadu
city: Pondicherry
country: India
facility: Aravind Eye Hospital
state: Tamil Nadu
Study officials:
affiliation: Proctor Foundation, University of California, San Francisco
name: Thomas M Lietman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Proctor Foundation, University of California, San Francisco
name: Nisha Acharya, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Aravind Eye Hospital, India
name: N V Prajna, MD
role: STUDY_DIRECTOR
References:
citation: Prajna NV, Mascarenhas J, Krishnan T, Reddy PR, Prajna L, Srinivasan M, Vaitilingam CM, Hong KC, Lee SM, McLeod SD, Zegans ME, Porco TC, Lietman TM, Acharya NR. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol. 2010 Jun;128(6):672-8. doi: 10.1001/archophthalmol.2010.102.