Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers

NCT ID: NCT02731638

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2018-07-31

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.

Conditions

Corneal Ulcer; Fungal Keratitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intrastromal voriconazole plus natamycin

Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis

Group Type: EXPERIMENTAL

Intrastromal voriconazole

Intervention Type: DRUG

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

Intervention Type: DRUG

Subjects will receive topical 5% natamycin drops hourly for 3 days.

Natamycin alone

Standard of care topical treatment for fungal keratitis

Group Type: ACTIVE_COMPARATOR

Natamycin

Intervention Type: DRUG

Subjects will receive topical 5% natamycin drops hourly for 3 days.

Interventions

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.

Intervention Type: DRUG

Natamycin

Subjects will receive topical 5% natamycin drops hourly for 3 days.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aravind Eye Hospitals, India

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Rose-Nussbaumer, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Francis I. Proctor Foundation at UCSF

San Francisco, California, United States

Aravind Eye Hospitals

Pondicherry, Tamil Nadu, India

Countries

United States; India

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

15-17989

Identifier Type: -

Identifier Source: org_study_id