Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers

Phase 3

Completed

• Conditions: Fungal Keratitis; Corneal Ulcer
• Interventions: Drug: Intrastromal voriconazole; Drug: Natamycin

• Registration Number: NCT02731638
• Lead Sponsor: University of California, San Francisco

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2016-03-14
• Study First Submitted QC: 2016-04-01
• Study First Posted: 2016-04-07
• Study Start: 2016-09
• Primary Completion: 2018-07
• Study Completion: 2018-07
• Results First Submitted: 2019-06-26
• Status Verified: 2019-09
• Results First Submitted QC: 2019-09-12
• Last Update Submitted: 2019-09-12
• Results First Posted: 2019-10-01
• Last Update Posted: 2019-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intrastromal voriconazole plus natamycin	Intrastromal voriconazole	Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis
Natamycin alone	Natamycin	Standard of care topical treatment for fungal keratitis
Intrastromal voriconazole plus natamycin	Natamycin	Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis

Primary Outcome Measures

Name	Time	Method
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus	3 days	Number of of participants with positive fungal cultures at 3 days

Secondary Outcome Measures

Name	Time	Method
Scar Size	3 weeks and 3 months	Scar size, geometric mean
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist	3 weeks and 3 months	Best spectacle-corrected visual acuity using calibrated Original Series Early Treatment Diabetic Retinopathy Study eye charts and recorded as number of letter read.
Corneal Neovascularization	3 months
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea	3 weeks and 3 months	Number of participants with scar depth at the anterior third (0-33% depth), middle third (\>33-67% depth), and posterior third (\>67-100% depth) of the cornea, as measured on slit lamp exam.
Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)	3 months
Corneal Thinning, as Measured by Pachymetry and OCT	6 months
Corneal Topography, as Measured by a Non-contact Imaging Topographer	6 months

Trial Locations

Locations (2)

Aravind Eye Hospitals; 🇮🇳 Pondicherry, Tamil Nadu, India

Francis I. Proctor Foundation at UCSF; 🇺🇸 San Francisco, California, United States