Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers (MALIN)
Primary Purpose
Corneal Ulcer, Fungal Keratitis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Intrastromal voriconazole
Natamycin
Sponsored by
About this trial
This is an interventional treatment trial for Corneal Ulcer focused on measuring cornea, ulcer, fungal, keratitis
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
Sites / Locations
- Francis I. Proctor Foundation at UCSF
- Aravind Eye Hospitals
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Intrastromal voriconazole plus natamycin
Natamycin alone
Arm Description
Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis
Standard of care topical treatment for fungal keratitis
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Scar Size
Scar size, geometric mean
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.
Corneal Thinning, as Measured by Pachymetry and OCT
Corneal Topography, as Measured by a Non-contact Imaging Topographer
Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)
Corneal Neovascularization
Full Information
NCT ID
NCT02731638
First Posted
March 14, 2016
Last Updated
September 12, 2019
Sponsor
University of California, San Francisco
Collaborators
Aravind Eye Hospitals, India
1. Study Identification
Unique Protocol Identification Number
NCT02731638
Brief Title
Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
Acronym
MALIN
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
July 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Aravind Eye Hospitals, India
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Ulcer, Fungal Keratitis
Keywords
cornea, ulcer, fungal, keratitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intrastromal voriconazole plus natamycin
Arm Type
Experimental
Arm Description
Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis
Arm Title
Natamycin alone
Arm Type
Active Comparator
Arm Description
Standard of care topical treatment for fungal keratitis
Intervention Type
Drug
Intervention Name(s)
Intrastromal voriconazole
Intervention Description
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
Intervention Name(s)
Natamycin
Intervention Description
Subjects will receive topical 5% natamycin drops hourly for 3 days.
Primary Outcome Measure Information:
Title
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus
Description
Number of of participants with positive fungal cultures at 3 days
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist
Description
Best spectacle-corrected visual acuity using calibrated Original Series Early Treatment Diabetic Retinopathy Study eye charts and recorded as number of letter read.
Time Frame
3 weeks and 3 months
Title
Scar Size
Description
Scar size, geometric mean
Time Frame
3 weeks and 3 months
Title
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
Description
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.
Time Frame
3 weeks and 3 months
Title
Corneal Thinning, as Measured by Pachymetry and OCT
Time Frame
6 months
Title
Corneal Topography, as Measured by a Non-contact Imaging Topographer
Time Frame
6 months
Title
Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)
Time Frame
3 months
Title
Corneal Neovascularization
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Rose-Nussbaumer, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Francis I. Proctor Foundation at UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Aravind Eye Hospitals
City
Pondicherry
State/Province
Tamil Nadu
Country
India
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified data will be input into a database using double data entry at UCSF. Data will be stored at UCSF for about 10 years.
Learn more about this trial
Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
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