Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers

NCT02731638 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 15-17989
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 2

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.

Conditions

Corneal Ulcer; Fungal Keratitis

Keywords

cornea; ulcer; fungal; keratitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist

  3 weeks and 3 months

• Scar Size

  3 weeks and 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

Other Outcomes (4)

• Corneal Neovascularization

  3 months

• 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

Study Arms (2)

Intrastromal voriconazole plus natamycin

EXPERIMENTAL

Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis

Drug: Intrastromal voriconazole; Drug: Natamycin

Natamycin alone

ACTIVE COMPARATOR

Standard of care topical treatment for fungal keratitis

Drug: Natamycin

Interventions

Intrastromal voriconazole 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.

Intrastromal voriconazole plus natamycin

Natamycin DRUG

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

Intrastromal voriconazole plus natamycin; Natamycin alone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Aravind Eye Hospitals, India: collaborator

Study Sites (2)

Francis I. Proctor Foundation at UCSF

San Francisco, California, 94143, United States

Location

Aravind Eye Hospitals

Pondicherry, Tamil Nadu, India

Location

MeSH Terms

Conditions

Corneal Ulcer; Corneal Diseases; Ulcer; Keratitis

Interventions

Natamycin

Condition Hierarchy (Ancestors)

Eye Infections; Infections; Eye Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Jennifer Rose-Nussbaumer
• Organization: University of California, San Francisco

jennifer.rose-nussbaumer@ucsf.edu

+1 415 502 2666

Study Officials

• Jennifer Rose-Nussbaumer, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: April 7, 2016
• Study Start: September 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: September 25, 2025
• Results First Posted: October 1, 2019

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1); IN (1)