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| Name | Class |
|---|---|
| Aravind Eye Hospitals, India | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intrastromal voriconazole plus natamycin | Experimental | Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis |
|
| Natamycin alone | Active Comparator | Standard of care topical treatment for fungal keratitis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Scar Size |
| Measure | Description | Time Frame |
|---|---|---|
| Corneal Neovascularization | As measured by clinical examination and slit lamp photographs. | 3 months |
| Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ) | 3 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Rose-Nussbaumer, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Francis I. Proctor Foundation at UCSF | San Francisco | California | 94143 | United States | ||
| Aravind Eye Hospitals |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intrastromal Voriconazole Plus Natamycin | Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis 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. |
| FG001 | Natamycin Alone | Standard of care topical treatment for fungal keratitis Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intrastromal Voriconazole Plus Natamycin | Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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-day culture results missing for one participant in the Natamycin group | Posted | Count of Participants | Participants | 3 days |
|
3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intrastromal Voriconazole Plus Natamycin | Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Endophthalmitis | Eye disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer Rose-Nussbaumer | University of California, San Francisco | +1 415 502 2666 | jennifer.rose-nussbaumer@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 17, 2017 | Jun 26, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 26, 2016 | Jun 26, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003320 | Corneal Ulcer |
| D003316 | Corneal Diseases |
| D014456 | Ulcer |
| D007634 | Keratitis |
| ID | Term |
|---|---|
| D015817 | Eye Infections |
| D007239 | Infections |
| D005128 | Eye Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D010866 | Natamycin |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Natamycin | Drug | Subjects will receive topical 5% natamycin drops hourly for 3 days. |
|
Scar size, geometric mean |
| 3 weeks and 3 months |
| 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 |
| Corneal Thinning, as Measured by Pachymetry and OCT | 6 months |
| Corneal Topography, as Measured by a Non-contact Imaging Topographer | 6 months |
| Pondicherry |
| Tamil Nadu |
| India |
| BG001 | Natamycin Alone | Standard of care topical treatment for fungal keratitis Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Occupation | Count of Participants | Participants |
|
| Trauma | Count of Participants | Participants |
|
| Affected Eye | Count of Participants | Participants |
|
| Visual Acuity, logMAR | Visual acuity in logarithm of the minimum angle of resolution (logMAR) units | Median | Inter-Quartile Range | logMAR |
|
| Ulcer location | Count of Participants | Participants |
|
| Hypopyon size (mm) | Count of Participants | Participants |
|
| Ulcer depth, measured in % depth | Count of Participants | Participants |
|
| Culture Results | Count of Participants | Participants |
|
Standard of care topical treatment for fungal keratitis Natamycin: Subjects will receive topical 5% natamycin drops hourly for 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-week visual acuity data was available for 65 people: 33 in the ISV group (2 lost to follow-up) and 32 in the Natamycin only group (3 lost of follow-up). 3-month visual acuity data was available for 58 people: 30 in the ISV group (5 lost to follow-up) and 28 in the Natamycin only group (7 lost to follow-up). | Posted | Mean | Standard Deviation | logarithm of the minimum angle (logMAR) | 3 weeks and 3 months |
|
|
|
|
| Secondary | Scar Size | Scar size, geometric mean | 3-week scar size data was available for 42 people: 24 in the ISV group (2 lost to follow-up [LTF], 9 unable to assess) and 18 in the Natamycin only group (3 LTF, 14 unable to assess). 3-month scar size data was available for 29 people: 16 in the ISV group (5 LTF, 14 unable to assess) and 13 in the Natamycin only group (7 LTF, 15 unable to assess). | Posted | Mean | Standard Deviation | millimeters squared | 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-week scar depth data was available for 40 people: 24 in the ISV group (2 lost to follow-up [LTF], 9 unable to assess) and 16 in the Natamycin only group (3 LTF, 16 unable to assess). 3-month scar depth was available for 29 people: 16 in the ISV group (5 LTF, 14 unable to assess) and 13 in the Natamycin only group (7 LTF, 15 unable to assess). | Posted | Count of Participants | Participants | 3 weeks and 3 months |
|
|
|
| Other Pre-specified | Corneal Neovascularization | As measured by clinical examination and slit lamp photographs. | Not Posted | 3 months | Participants |
| Other Pre-specified | Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ) | Not Posted | 3 months | Participants |
| Other Pre-specified | Corneal Thinning, as Measured by Pachymetry and OCT | Not Posted | 6 months | Participants |
| Other Pre-specified | Corneal Topography, as Measured by a Non-contact Imaging Topographer | Not Posted | 6 months | Participants |
| 0 |
| 35 |
| 0 |
| 35 |
| 16 |
| 35 |
| EG001 | Natamycin Alone | Standard of care topical treatment for fungal keratitis Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days. | 0 | 35 | 0 | 35 | 15 | 35 |
| Glaucoma | Eye disorders | Systematic Assessment |
|
| Hypopyon | Eye disorders | Systematic Assessment |
|
| Medication Reaction | Eye disorders | Systematic Assessment |
|
| Nonhealing Ulcer | Eye disorders | Systematic Assessment |
|
| Perforation | Eye disorders | Systematic Assessment |
|
| Progressive Corneal Thinning | Eye disorders | Systematic Assessment |
|
| Therapeutic Penetrating Keratoplasty | Eye disorders | Systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| 3 months |
|
|
| 0.75 |
| Coefficient |
| 0.5 |
| 2-Sided |
| 95 |
| -2.6 |
| 3.6 |
Positive coefficients of the logMAR value indicate worsened visual acuity |
| Superiority |
| 3 Months |
|
|
| Middle third |
|
| Posterior third |
|
| 3 Months |
|
|