Mycotic Ulcer Treatment Trial I (MUTT I)

University of California San Francisco (UCSF)

Status and phase

Completed

Phase 3

Conditions

Eye Infections, Fungal

Corneal Ulcer

Treatments

Drug: Natamycin

Drug: Voriconazole

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00996736

U10EY018573-01A1 (U.S. NIH Grant/Contract)

H9332-33965-02

Details and patient eligibility

About

The purpose of this study is to determine if natamycin or voriconazole results in better visual outcomes in fungal corneal ulcers, especially visual acuity.

Full 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 natamycin or voriconazole results in better outcomes for fungal corneal ulcers. 368 fungal corneal ulcers with baseline visual acuity between 6/12 (20/40, logMAR 0.3) and 6/120 (20/400, logMAR 1.3) presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive either topical natamycin or topical voriconazole. The primary outcome is best spectacle-corrected logMAR visual acuity three months after enrollment, using best spectacle-corrected enrollment visual acuity as a co-variate.

Enrollment

323 patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Presence of a corneal ulcer at presentation
Evidence of filamentous fungus on smear (KOH wet mount, Giemsa, or Gram stain)
Visual acuity between 6/12 (20/40, logMAR 0.3) and 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

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 (2/200) in the fellow eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA 6/60 or better qualifies for enrollment)
Acuity worse than 6/120 (20/400) or better than 6/12 (20/40) in the study eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA can be used for enrollment)
Known allergy to study medications (antifungal or preservative)
No light perception in the affected eye
Not willing to participate