Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers

Corneal Ulcer Clinical Trial

— MALIN  

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02731638
• Other study ID #: 15-17989
• Status: Completed
• Phase: Phase 3
• Start date: September 2016
• Est. completion date: July 2018

Study information

• Verified date: September 2019
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Corneal Ulcer
• Fungal Keratitis
• Keratitis
• Ulcer

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
India	Aravind Eye Hospitals	Pondicherry	Tamil Nadu
United States	Francis I. Proctor Foundation at UCSF	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Aravind Eye Hospitals, India

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus	Number of of participants with positive fungal cultures at 3 days	3 days
Secondary	Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist	Best spectacle-corrected visual acuity using calibrated Original Series Early Treatment Diabetic Retinopathy Study eye charts and recorded as number of letter read.	3 weeks and 3 months
Secondary	Scar Size	Scar size, geometric mean	3 weeks and 3 months
Secondary	Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea	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.	3 weeks and 3 months
Secondary	Corneal Thinning, as Measured by Pachymetry and OCT		6 months
Secondary	Corneal Topography, as Measured by a Non-contact Imaging Topographer		6 months
Secondary	Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)		3 months
Secondary	Corneal Neovascularization		3 months