Clinical trial NCT02731638: Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
Official title: Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Corneal Ulcer
Fungal Keratitis
Keywords: cornea
ulcer
fungal
keratitis
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Aravind Eye Hospitals, India
First posted: 2016-04-07
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus
timeFrame: 3 days
Secondary outcomes:
measure: Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist
timeFrame: 3 weeks and 3 months
measure: Scar Size
timeFrame: 3 weeks and 3 months
measure: Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
timeFrame: 3 weeks and 3 months
measure: Corneal Thinning, as Measured by Pachymetry and OCT
timeFrame: 6 months
measure: Corneal Topography, as Measured by a Non-contact Imaging Topographer
timeFrame: 6 months
measure: Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)
timeFrame: 3 months
measure: Corneal Neovascularization
timeFrame: 3 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Francis I. Proctor Foundation at UCSF
state: California
city: Pondicherry
country: India
facility: Aravind Eye Hospitals
state: Tamil Nadu
Study officials:
affiliation: Stanford University
name: Jennifer Rose-Nussbaumer, MD
role: PRINCIPAL_INVESTIGATOR
References: