Overview

This trial is active, not recruiting.

Conditions corneal ulcer, fungal keratitis
Treatments intrastromal voriconazole, natamycin
Phase phase 3
Sponsor University of California, San Francisco
Collaborator Aravind Eye Hospitals, India
Start date February 2016
End date August 2018
Trial size 70 participants
Trial identifier NCT02731638, 15-17989

Summary

Mycotic Antimicrobial Localized Injection (MALIN) is a randomized, masked, two-arm clinical trial investigating intrastromal voriconazole in the treatment of fungal corneal ulcers. There is currently little evidence to guide the treatment of fungal keratitis beyond topical anti-fungal drops, though intrastromal voriconazole and oral antifungal treatments are used as well. This study will provide evidence to guide the treatment of fungal keratitis in the future. The purpose of this study is to determine differences in microbiological cure for 3-day repeat cultures between different antifungal treatments. For this study, there will be 1:1 randomization to one of these two treatment groups: 1) topical natamycin plus intrastromal voriconazole injection or 2) topical natamycin alone.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking single blind (investigator)
Primary purpose treatment
Arm
(Experimental)
Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis
intrastromal voriconazole
Subjects will receive three intrastromal voriconazole injections over 10 days. Intrastromal voriconazole injection is a routine procedure performed by Aravind Eye Hospital for fungal keratitis.
natamycin
Subjects will receive topical 5% natamycin drops hourly for 3 days.
(Active Comparator)
Standard of care topical treatment for fungal keratitis
natamycin
Subjects will receive topical 5% natamycin drops hourly for 3 days.

Primary Outcomes

Measure
Culture positivity at day 3 using potassium hydroxide (KOH) wet mount to test for fungus
time frame: 3 days

Secondary Outcomes

Measure
Best spectacle-corrected visual acuity, as measured by a refractionist
time frame: 3 months
Scar size, as measured by clinical exam, slit lamp photographs, and optical coherence tomography (OCT)
time frame: 6 months
Scar depth, as measured by clinical exam, slit lamp photographs, and OCT
time frame: 6 months
Adverse events including rate of perforation/need for therapeutic penetrating keratoplasty (TPK)
time frame: 6 months
Corneal thinning, as measured by pachymetry and OCT
time frame: 6 months
Corneal topography, as measured by a non-contact imaging topographer
time frame: 6 months
Change in quality of life, measured by the Indian Vision Function Questionnaire (IND-VFQ)
time frame: 3 months
Corneal neovascularization, as measured by clinical examination and slit lamp photographs
time frame: 6 months

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

Inclusion Criteria: - Moderate to severe corneal ulcer that is smear positive for filamentous fungus - Pinhole visual acuity worse than 20/70 in affected eye - Basic understanding of the study as determined by the physician - Commitment to return for follow up visits Exclusion Criteria: - Gram stain positive for bacteria or evidence of other concomitant infection (i.e. herpes, acanthamoeba) - Impending or frank perforation at recruitment - Involvement of sclera at presentation - Non-infectious or autoimmune keratitis - History of corneal transplantation or recent intraocular surgery - No light perception in the affected eye - Pinhole visual acuity worse than 20/200 in the unaffected eye - Pregnant women - Participants who are decisionally and/or cognitively impaired

Additional Information

Principal investigator Jennifer Rose-Nussbaumer, MD
Description The proposed study is a randomized controlled trial to determine whether intrastromal voriconazole improves outcomes in fungal keratitis. Patients presenting to the Aravind Eye Hospitals in Pondicherry, India for treatment of fungal keratitis will be recruited for the proposed study. Approximately 70 patients will be enrolled in the study. Subjects presenting with fungal keratitis will be randomized to receive topical natamycin plus intrastromal voriconazole or to receive topical natamycin alone. Subjects may also receive oral antifungals after day 3 at the discretion of the treating clinician. All study subjects will be followed for 3 months to evaluate response to treatment. Investigators from the University of California, San Francisco (UCSF) will assist Aravind Eye Hospital with the study design, implementation, and analysis of the research, and will help fund the study. The investigators will visit Aravind to help with the study implementation. UCSF will play an important role in this study by assisting with the study design, implementation, analysis, and funding.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by University of California, San Francisco.