Trial Outcomes & Findings for Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers (NCT NCT02731638)
NCT ID: NCT02731638
Last Updated: 2025-09-25
Results Overview
Number of of participants with positive fungal cultures at 3 days
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
70 participants
Primary outcome timeframe
3 days
Results posted on
2025-09-25
Participant Flow
Participant milestones
| Measure |
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.
|
Natamycin Alone
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
35
|
|
Overall Study
COMPLETED
|
29
|
26
|
|
Overall Study
NOT COMPLETED
|
6
|
9
|
Reasons for withdrawal
| Measure |
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.
|
Natamycin Alone
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
6
|
9
|
Baseline Characteristics
Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers
Baseline characteristics by cohort
| Measure |
Intrastromal Voriconazole Plus Natamycin
n=35 Participants
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.
|
Natamycin Alone
n=35 Participants
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53 years
n=99 Participants
|
55 years
n=107 Participants
|
55 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
35 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
70 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
India
|
35 participants
n=99 Participants
|
35 participants
n=107 Participants
|
70 participants
n=206 Participants
|
|
Occupation
Agriculture
|
11 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Occupation
Non-Agriculture
|
22 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Occupation
Unknown
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Trauma
Stick
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Trauma
Leaf
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Trauma
Finger
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Trauma
Dust
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Trauma
Mud
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Trauma
Insect
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Trauma
Other
|
4 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Trauma
Unknown object
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Trauma
No trauma
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Affected Eye
Right
|
15 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
|
Affected Eye
Left
|
20 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Visual Acuity, logMAR
|
1.7 logMAR
n=99 Participants
|
1.7 logMAR
n=107 Participants
|
1.7 logMAR
n=206 Participants
|
|
Ulcer location
Central
|
30 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
62 Participants
n=206 Participants
|
|
Ulcer location
Peripheral
|
5 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Hypopyon size (mm)
None
|
16 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
Hypopyon size (mm)
<0.5mm
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Hypopyon size (mm)
≥0.5mm
|
13 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Ulcer depth, measured in % depth
>0-33%
|
13 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Ulcer depth, measured in % depth
>33-67%
|
11 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Ulcer depth, measured in % depth
>67-100%
|
11 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Culture Results
Fusarium species
|
8 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Culture Results
Aspergillus species
|
7 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Culture Results
Curvularia species
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Culture Results
Exserohilum species
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Culture Results
Unidentified hyaline
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Culture Results
Unidentified dematiaceous
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Culture Results
Fungal culture negative
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Culture Results
Missing
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 3 daysPopulation: 3-day culture results missing for one participant in the Natamycin group
Number of of participants with positive fungal cultures at 3 days
Outcome measures
| Measure |
Intrastromal Voriconazole Plus Natamycin
n=35 Participants
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.
|
Natamycin Alone
n=34 Participants
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus
|
14 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: 3 weeks and 3 monthsPopulation: 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).
Best spectacle-corrected visual acuity using calibrated Original Series Early Treatment Diabetic Retinopathy Study eye charts and recorded as number of letter read.
Outcome measures
| Measure |
Intrastromal Voriconazole Plus Natamycin
n=33 Participants
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.
|
Natamycin Alone
n=32 Participants
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist
3 weeks
|
1.39 logarithm of the minimum angle (logMAR)
Standard Deviation 0.59
|
1.23 logarithm of the minimum angle (logMAR)
Standard Deviation 0.65
|
|
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist
3 months
|
1.30 logarithm of the minimum angle (logMAR)
Standard Deviation 0.60
|
1.28 logarithm of the minimum angle (logMAR)
Standard Deviation 0.66
|
SECONDARY outcome
Timeframe: 3 weeks and 3 monthsPopulation: 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).
Scar size, geometric mean
Outcome measures
| Measure |
Intrastromal Voriconazole Plus Natamycin
n=24 Participants
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.
|
Natamycin Alone
n=18 Participants
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Scar Size
3 Weeks
|
4.8 millimeters squared
Standard Deviation 1.2
|
4.1 millimeters squared
Standard Deviation 1.3
|
|
Scar Size
3 Months
|
4.9 millimeters squared
Standard Deviation 1.2
|
4.5 millimeters squared
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: 3 weeks and 3 monthsPopulation: 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).
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.
Outcome measures
| Measure |
Intrastromal Voriconazole Plus Natamycin
n=24 Participants
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.
|
Natamycin Alone
n=16 Participants
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
3 Weeks · Anterior third
|
9 Participants
|
13 Participants
|
|
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
3 Weeks · Middle third
|
8 Participants
|
2 Participants
|
|
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
3 Weeks · Posterior third
|
7 Participants
|
1 Participants
|
|
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
3 Months · Anterior third
|
6 Participants
|
7 Participants
|
|
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
3 Months · Middle third
|
5 Participants
|
2 Participants
|
|
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea
3 Months · Posterior third
|
5 Participants
|
4 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 monthsAs measured by clinical examination and slit lamp photographs.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 monthsOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
Adverse Events
Intrastromal Voriconazole Plus Natamycin
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Natamycin Alone
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Intrastromal Voriconazole Plus Natamycin
n=35 participants at risk
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.
|
Natamycin Alone
n=35 participants at risk
Standard of care topical treatment for fungal keratitis
Natamycin: Subjects will receive topical 5% natamycin drops hourly for 3 days.
|
|---|---|---|
|
Eye disorders
Endophthalmitis
|
0.00%
0/35 • 3 months
|
5.7%
2/35 • 3 months
|
|
Eye disorders
Glaucoma
|
11.4%
4/35 • 3 months
|
5.7%
2/35 • 3 months
|
|
Eye disorders
Hypopyon
|
8.6%
3/35 • 3 months
|
0.00%
0/35 • 3 months
|
|
Eye disorders
Medication Reaction
|
0.00%
0/35 • 3 months
|
2.9%
1/35 • 3 months
|
|
Eye disorders
Nonhealing Ulcer
|
8.6%
3/35 • 3 months
|
0.00%
0/35 • 3 months
|
|
Eye disorders
Perforation
|
22.9%
8/35 • 3 months
|
8.6%
3/35 • 3 months
|
|
Eye disorders
Progressive Corneal Thinning
|
2.9%
1/35 • 3 months
|
0.00%
0/35 • 3 months
|
|
Eye disorders
Therapeutic Penetrating Keratoplasty
|
40.0%
14/35 • 3 months
|
37.1%
13/35 • 3 months
|
Additional Information
Dr. Jennifer Rose-Nussbaumer
University of California, San Francisco
Phone: +1 415 502 2666
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place