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CompletedNCT02731638MALINUpdated Sep 25, 2025Results posted

Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers

A Phase 3 interventional study of Intrastromal voriconazole and Natamycin in Corneal Ulcer and Fungal Keratitis, sponsored by University of California, San Francisco. Completed at 2 sites in 2 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-09-25.

Sponsored by University of California, San Francisco · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
70
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Corneal Ulcer
  • Fungal Keratitis

Keywords

  • cornea
  • ulcer
  • fungal
  • keratitis
03

In context

Corneal Ulcer

63 studies on the registry are indexed under Corneal Ulcer; 8 are open to participants now.

This study's enrollment of 70 is above the median of 60 across 45 interventional studies indexed under Corneal Ulcer.

Browse Corneal Ulcer studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.

Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) have results posted.

Browse University of California, San Francisco studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 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
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Investigator)
Enrollment
70 participants (actual)

Study arms

  • Experimental
    Intrastromal voriconazole plus natamycin

    Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis

    Drug: Intrastromal voriconazole · Drug: Natamycin

  • Active comparator
    Natamycin alone

    Standard of care topical treatment for fungal keratitis

    Drug: Natamycin

Interventions

  • DrugIntrastromal 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.

  • DrugNatamycin

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

06

What researchers measure

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

    Time frame: 3 days

Secondary outcomes

  1. 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.

    Time frame: 3 weeks and 3 months

  2. Scar Size

    Scar size, geometric mean

    Time frame: 3 weeks and 3 months

  3. 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.

    Time frame: 3 weeks and 3 months

Other outcomes

  1. Corneal Neovascularization

    As measured by clinical examination and slit lamp photographs.

    Time frame: 3 months

  2. Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)

    Time frame: 3 months

  3. Corneal Thinning, as Measured by Pachymetry and OCT

    Time frame: 6 months

  4. Corneal Topography, as Measured by a Non-contact Imaging Topographer

    Time frame: 6 months

07

Results

Posted Oct 1, 2019

Participant flow

Participant flow — Overall Study
MilestoneIntrastromal Voriconazole Plus NatamycinNatamycin Alone
Started3535
Completed2926
Not completed69
Withdrew: Lost to follow-up69

Outcome measures

PrimaryCulture 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

Time frame:
3 days
Reported as:
Count of participants · Participants
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus
ParticipantsIntrastromal Voriconazole Plus NatamycinNatamycin Alone
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus1411
Statistical analysis
  • Intrastromal Voriconazole Plus Natamycin vs Natamycin Alone · Regression, Logistic · p = 0.26 · Odds ratio (or): 1.82 · 95% CI 0.65 to 5.23Bias-corrected logistic regression, accounting for baseline culture status
SecondaryBest 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.

Time frame:
3 weeks and 3 months
Reported as:
Mean · logarithm of the minimum angle (logMAR)
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist
logarithm of the minimum angle (logMAR)Intrastromal Voriconazole Plus NatamycinNatamycin Alone
3 weeks1.39 ± 0.591.23 ± 0.65
3 months1.30 ± 0.601.28 ± 0.66
Statistical analysis
  • Intrastromal Voriconazole Plus Natamycin vs Natamycin Alone · Regression, Linear · p = 0.25 · Coefficient: 1.6 · 95% CI -1.2 to 4.4Positive coefficients of the logMAR value indicated worsened visual acuity
  • Intrastromal Voriconazole Plus Natamycin vs Natamycin Alone · Regression, Linear · p = 0.75 · Coefficient: 0.5 · 95% CI -2.6 to 3.6Positive coefficients of the logMAR value indicate worsened visual acuity
SecondaryScar Size

Scar size, geometric mean

Time frame:
3 weeks and 3 months
Reported as:
Mean · millimeters squared
Scar Size
millimeters squaredIntrastromal Voriconazole Plus NatamycinNatamycin Alone
3 Weeks4.8 ± 1.24.1 ± 1.3
3 Months4.9 ± 1.24.5 ± 1.1
SecondaryNumber 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.

Time frame:
3 weeks and 3 months
Reported as:
Count of participants · Participants
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
ParticipantsIntrastromal Voriconazole Plus NatamycinNatamycin Alone
3 Weeks — Anterior third913
3 Weeks — Middle third82
3 Weeks — Posterior third71
3 Months — Anterior third67
3 Months — Middle third52
3 Months — Posterior third54
Other pre-specifiedCorneal Neovascularization

As measured by clinical examination and slit lamp photographs.

Time frame:
3 months

Results for this outcome have not been posted.

Other pre-specifiedChange in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)
Time frame:
3 months

Results for this outcome have not been posted.

Other pre-specifiedCorneal Thinning, as Measured by Pachymetry and OCT
Time frame:
6 months

Results for this outcome have not been posted.

Other pre-specifiedCorneal Topography, as Measured by a Non-contact Imaging Topographer
Time frame:
6 months

Results for this outcome have not been posted.

Adverse events

Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intrastromal Voriconazole Plus Natamycin0/35 (0%)0/35 (0%)16/35 (45.7%)
Natamycin Alone0/35 (0%)0/35 (0%)15/35 (42.9%)
Most frequent other events
Most frequent other events
EventIntrastromal Voriconazole Plus NatamycinNatamycin Alone
Therapeutic Penetrating KeratoplastyEye disorders14/3513/35
PerforationEye disorders8/353/35
GlaucomaEye disorders4/352/35
HypopyonEye disorders3/350/35
Nonhealing UlcerEye disorders3/350/35
EndophthalmitisEye disorders0/352/35
Medication ReactionEye disorders0/351/35
Progressive Corneal ThinningEye disorders1/350/35

Baseline characteristics

Age, Continuous
Age, Continuous(years)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
Median53 (42 to 60)55 (41 to 62)55 (43 to 60)
Sex: Female, Male
Sex: Female, Male(Participants)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
Female91726
Male261844
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
American Indian or Alaska Native000
Asian353570
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
India353570
Occupation
Occupation(Participants)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
Agriculture111526
Non-Agriculture221739
Unknown235
Trauma
Trauma(Participants)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
Stick7310
Leaf213
Finger011
Dust347
Mud448
Insect516
Other4913
Unknown object022
No trauma101020
Affected Eye
Affected Eye(Participants)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
Right151732
Left201838
Visual Acuity, logMAR
Visual Acuity, logMAR(logMAR)Intrastromal Voriconazole Plus NatamycinNatamycin AloneTotal
Median1.7 (1.6 to 1.8)1.7 (1.6 to 1.8)1.7 (1.6 to 1.8)

4 further baseline measures are reported on the registry.

08

Study locations

2 sites
  • Francis I. Proctor Foundation at UCSF
    San Francisco, California 94143, United States
  • Aravind Eye Hospitals
    Pondicherry, Tamil Nadu, India
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — 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.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Sep 2016 to primary completion in Jul 2018, 22 months.

Results were first posted in Oct 2019, 1 year 3 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 14, 2016
First posted
Apr 7, 2016
StartActual
Sep 2016
Primary completionActual
Jul 2018
CompletionActual
Jul 2018
Results first posted
Oct 1, 2019
Last update
Sep 25, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 25, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02731638
Lead sponsor
University of California, San Francisco
Collaborators
Aravind Eye Hospitals, India
Responsible party
Sponsor
First posted
Apr 7, 2016
Start date
Sep 2016
Primary completion
Jul 2018
Completion
Jul 2018
Results posted
Oct 1, 2019
Last update
Sep 25, 2025

Study contacts

Jennifer Rose-Nussbaumer, MD
principal investigator · Stanford University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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