Corneal UlcerPhase 3MALINNCT02731638
Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
A Phase 3 study testing Intrastromal voriconazole and Natamycin in people with Corneal Ulcer and Fungal Keratitis, run by University of California, San Francisco at 2 sites in 2 countries.
Trial summary
Mycotic Antimicrobial Localized Injection (MALIN) is a randomized, masked, two-arm clinical trial investigating intrastromal voriconazole in the treatment of fungal corneal ulcers. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Corneal Ulcer, Fungal Keratitis
- What is being tested?
- Intrastromal voriconazole and Natamycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2016to Jul 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Pinhole visual acuity worse than 20/200 in the unaffected eye
- Pregnant women
- Participants who are decisionally and/or cognitively impaired
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Francis I. Proctor Foundation at UCSF
San Francisco, California, 94143
About this study
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.
- Conditions
- Corneal Ulcer, Fungal Keratitis
- Being tested
- Intrastromal voriconazole, Natamycin
- Keywords
- cornea, ulcer, fungal, keratitis
- Medical subject headings
- Corneal Ulcer, Corneal Diseases, Ulcer, Keratitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrastromal voriconazoleDrug
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.
NatamycinDrug
Subjects will receive topical 5% natamycin drops hourly for 3 days.
| Study group | Role | What they receive |
|---|---|---|
| Intrastromal voriconazole plus natamycin | Experimental | Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis Receives: Drug: Intrastromal voriconazole; Drug: Natamycin |
| Natamycin alone | Active comparator | Standard of care topical treatment for fungal keratitis Receives: Drug: Natamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 days
Secondary outcomes (3)
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.
Measured: 3 weeks and 3 months
Scar Size
Scar size, geometric mean
Measured: 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.
Measured: 3 weeks and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2016 (estimated)
- Study startSep 2016
- Primary completionJul 2018
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Corneal UlcerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Aravind Eye Hospitals, India
- Responsible party
- Sponsor
- Investigators
- Jennifer Rose-Nussbaumer, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02731638
- Sponsor's protocol ID
- 15-17989
- Acronym
- MALIN
- Status last verified
- Sep 2025
- First submitted
- 14 Mar 2016
- Last updated
- 25 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
- ClinicalTrials.gov ID
- NCT02731638
- Acronym / sponsor ID
- MALIN / 15-17989
- Conditions
- Corneal Ulcer, Fungal Keratitis
- Keywords
- cornea, ulcer, fungal, keratitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Aravind Eye Hospitals, India
- Study start
- Sep 2016 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 7 Apr 2016 (estimated)
- Results
- Posted 1 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intrastromal voriconazole plus natamycin | Experimental | Drug: Intrastromal voriconazole, Drug: NatamycinIntrastromal voriconazole plus standard of care topical treatment for fungal keratitis |
| Natamycin alone | Active comparator | Drug: NatamycinStandard of care topical treatment for fungal keratitis |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrastromal voriconazoleSubjects will receive three intrastromal voriconazole injections over 10 days. Intrastromal voriconazole injection is a routine procedure performed by Aravind Eye Hospital for fungal keratitis. | Drug | Intrastromal voriconazole plus natamycin |
| NatamycinSubjects will receive topical 5% natamycin drops hourly for 3 days. | Drug | Intrastromal voriconazole plus natamycin, Natamycin alone |
Primary outcome
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus
Time frame: 3 days
Number of of participants with positive fungal cultures at 3 days
3 secondary outcomes
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist
Time frame: 3 weeks and 3 months
Scar Size
Time frame: 3 weeks and 3 months
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
Time frame: 3 weeks and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Rose-Nussbaumer, MD principal investigator
Stanford University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intrastromal voriconazole and Natamycin in people with Corneal Ulcer and Fungal Keratitis, run by University of California, San Francisco at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus (time frame: 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.