Overview

This trial is active, not recruiting.

Conditions corneal ulcer, eye infections, fungal
Treatments voriconazole, placebo
Phase phase 3
Sponsor University of California, San Francisco
Collaborator Aravind Eye Hospitals, India
Start date May 2010
End date January 2016
Trial size 240 participants
Trial identifier NCT00997035, H9332-33965-02_2, U10EY018573-01A1

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
voriconazole
1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment. 5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment. 400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing <40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.
(Placebo Comparator)
placebo
1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment. 5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment. Two tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.

Primary Outcomes

Measure
Rate of perforation
time frame: 3 months from enrollment

Secondary Outcomes

Measure
Best spectacle-corrected logMAR visual acuity
time frame: 3 weeks after enrollment
Best spectacle-corrected logMAR visual acuity only in Indian sites
time frame: 3 weeks and 3 months after enrollment
Best spectacle-corrected logMAR visual acuity
time frame: 3 months after enrollment
Hard contact-lens corrected visual acuity measured in logMAR
time frame: 3 months after enrollment
Size of infiltrate/scar
time frame: 3 weeks and 3 months after enrollment
Time to resolution of epithelial defect
time frame: At the time of resolution of epithelial defect
Number of adverse events
time frame: At the time of adverse event
Minimum inhibitory concentration of isolates
time frame: 3 months after enrollment
Microbiological cure at 7 days
time frame: 7 days after enrollment

Eligibility Criteria

Male or female participants at least 16 years old.

Inclusion Criteria: - 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 Exclusion Criteria: - 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

Additional Information

Official title Mycotic Ulcer Treatment Trial
Principal investigator NV Prajna, DNB, FRC Ophth
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by University of California, San Francisco.