Trial Outcomes & Findings for Therapeutic Exploratory Study of Comparing Natamycin and Voriconazole to Treat Fungal Corneal Ulcer (NCT NCT00557362)
NCT ID: NCT00557362
Last Updated: 2018-08-07
Results Overview
The primary efficacy endpoint was BSCVA at 3 months in the study eye, using a linear regression model with 3-month BSCVA measured in logMAR (logarithm of the Minimum Angle of Resolution) as the outcome variable and treatment arm (voriconazole vs natamycin) and enrollment logMAR BSCVA and corneal de-epithelialization (yes or no) as covariates.
COMPLETED
PHASE1/PHASE2
120 participants
3 months from enrollment
2018-08-07
Participant Flow
From November 27, 2007 to May 12, 2008, all patients with a corneal ulcer presenting to Aravind Eye Hospital's cornea clinics in Madurai and Pondicherry, India, were evaluated for eligibility. The Aravind Eye Care System is both a primary and tertiary care eye hospital in South India with a well-established cornea subspecialty clinic.
All patients with a corneal ulcer had corneal scrapings using a Kimura spatula for Gram stain and potassium hydroxide wet mount and had cultures plated on blood, chocolate, and potato dextrose agar. If all inclusion criteria and no exclusion criteria were met, the patient was enrolled in the study.
Participant milestones
| Measure |
Topical Natamycin With Corneal De-epithelialization
Topical natamycin with corneal de-epithelialization.
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Natamycin Without Corneal De-epithelialization
Topical natamycin without corneal de-epithelialization.
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Voriconazole With Corneal De-epithelialization
Topical voriconazole with corneal de-epithelialization.
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Voriconazole Without Corneal De-epithelialization
Topical voriconazole without corneal de-epithelialization.
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
30
|
30
|
30
|
30
|
|
Overall Study
COMPLETED
|
28
|
28
|
26
|
27
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
4
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Therapeutic Exploratory Study of Comparing Natamycin and Voriconazole to Treat Fungal Corneal Ulcer
Baseline characteristics by cohort
| Measure |
Topical Voriconazole With Corneal De-epithelialization
n=30 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution. One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Voriconazole Without Corneal De-epithelialization
n=30 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution. One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin With Corneal De-epithelialization
n=30 Participants
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Natamycin Without Corneal De-epithelialization
n=30 Participants
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
47.0 years
STANDARD_DEVIATION 14.5 • n=39 Participants
|
45.0 years
STANDARD_DEVIATION 14.5 • n=41 Participants
|
49.8 years
STANDARD_DEVIATION 11.9 • n=35 Participants
|
45.9 years
STANDARD_DEVIATION 13.1 • n=31 Participants
|
46.93 years
STANDARD_DEVIATION 13.72 • n=146 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=39 Participants
|
9 Participants
n=41 Participants
|
7 Participants
n=35 Participants
|
11 Participants
n=31 Participants
|
41 Participants
n=146 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=39 Participants
|
21 Participants
n=41 Participants
|
23 Participants
n=35 Participants
|
19 Participants
n=31 Participants
|
79 Participants
n=146 Participants
|
|
Region of Enrollment
India
|
30 participants
n=39 Participants
|
30 participants
n=41 Participants
|
30 participants
n=35 Participants
|
30 participants
n=31 Participants
|
120 participants
n=146 Participants
|
|
Enrollment logMAR BSCVA
|
0.94 logMAR
STANDARD_DEVIATION 0.66 • n=39 Participants
|
0.96 logMAR
STANDARD_DEVIATION 0.66 • n=41 Participants
|
0.87 logMAR
STANDARD_DEVIATION 0.67 • n=35 Participants
|
0.94 logMAR
STANDARD_DEVIATION 0.61 • n=31 Participants
|
0.93 logMAR
STANDARD_DEVIATION 0.64 • n=146 Participants
|
PRIMARY outcome
Timeframe: 3 months from enrollmentThe primary efficacy endpoint was BSCVA at 3 months in the study eye, using a linear regression model with 3-month BSCVA measured in logMAR (logarithm of the Minimum Angle of Resolution) as the outcome variable and treatment arm (voriconazole vs natamycin) and enrollment logMAR BSCVA and corneal de-epithelialization (yes or no) as covariates.
Outcome measures
| Measure |
Topical Voriconazole
n=60 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin
n=60 Participants
Drug: Natamycin 5%
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|
|
Best Spectacle Corrected Visual Acuity (BSCVA) 3 Months After Enrollment, Adjusting for Enrollment BSCVA in a Multiple Linear Regression Model
|
0.61 logMAR
Interval 0.48 to 0.74
|
0.71 logMAR
Interval 0.57 to 0.84
|
SECONDARY outcome
Timeframe: 3 months from enrollmentResolution of epithelial defect was defined as the absence of an epithelial defect with administration of fluorescein. The time to re-epithelialization was compared between the voriconazole and natamycin groups using the Cox proportional hazards model, adjusting for baseline epithelial defect size.
Outcome measures
| Measure |
Topical Voriconazole
n=60 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin
n=60 Participants
Drug: Natamycin 5%
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|
|
Time to Resolution of Epithelial Defect
|
13.07 days
Standard Deviation 7.71
|
15.2 days
Standard Deviation 7.03
|
SECONDARY outcome
Timeframe: 3 months from enrollmentSize of infiltrate/scar post-treatment was analyzed in a linear regression model using enrollment infiltrate/scar size as a covariate. No differentiation was made between infiltrate and scar when measuring infiltrate/scar size (measured in mm). For analysis, infiltrate/scar size was characterized by the geometric mean of the longest dimension and the longest perpendicular.
Outcome measures
| Measure |
Topical Voriconazole
n=51 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin
n=55 Participants
Drug: Natamycin 5%
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|
|
Size of Infiltrate/Scar Post-treatment Was Analyzed in a Linear Regression Model Using Enrollment Infiltrate/Scar Size as a Covariate.
|
4.21 mm
Interval 3.93 to 4.49
|
4.08 mm
Interval 3.81 to 4.35
|
SECONDARY outcome
Timeframe: 3 months from enrollmentPopulation: This analysis looks at two different subgroups - Fusarium ulcers and Aspergillus ulcers. There were 44 Fusaruim ulcers enrolled in this trial and analyzed here, 23 of which were randomized to voriconazole and 21 to natamycin. There were 19 Aspergillus ulcers analyzed here, 8 of which were randomized to voriconazole and 11 to natamycin.
Two subgroup analyses were conducted by causative organism: 1) best spectacle-corrected visual acuity (BSCVA) by treatment arm among Fusarium ulcers; 2) best spectacle-corrected visual acuity (BSCVA) by treatment arm among Aspergillus ulcers.
Outcome measures
| Measure |
Topical Voriconazole
n=31 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin
n=32 Participants
Drug: Natamycin 5%
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|
|
Subgroup Analysis - Best Spectacle-corrected Visual Acuity Examined by Voriconazole and Natamycin Treatment Arms in Subgroups of Fungal Ulcers (Fusarium Spp and Aspergillus Spp).
BSCVA Fusarium ulcers (n=23 vori; n=21 nata)
|
0.58 logMAR
Interval 0.36 to 0.81
|
0.50 logMAR
Interval 0.27 to 0.74
|
|
Subgroup Analysis - Best Spectacle-corrected Visual Acuity Examined by Voriconazole and Natamycin Treatment Arms in Subgroups of Fungal Ulcers (Fusarium Spp and Aspergillus Spp).
BSCVA Aspergillus ulcers (n=8 vori; n=11 nata)
|
0.48 logMAR
Interval 0.2 to 0.76
|
0.68 logMAR
Interval 0.44 to 0.92
|
SECONDARY outcome
Timeframe: 3 months from enrollmentBest hard contact lens-corrected visual acuity 3 months after enrollment was evaluated in a multiple linear regression model with enrollment hard contact lens-corrected visual acuity as a covariate. Visual acuity is reported in logMAR (logarithm of the Minimum Angle of Resolution).
Outcome measures
| Measure |
Topical Voriconazole
n=38 Participants
Drug: Voriconazole Voriconazole prepared as a 1% solution.
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin
n=40 Participants
Drug: Natamycin 5%
One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|
|
Best Hard Contact Lens-corrected Visual Acuity 3 Months After Enrollment in a Multiple Linear Regression Model With Enrollment Hard Contact Lens-corrected Visual Acuity as a Covariate
|
0.39 logMAR
Interval 0.26 to 0.54
|
0.46 logMAR
Interval 0.32 to 0.6
|
Adverse Events
Topical Voriconazole With Corneal De-epithelialization
Topical Voriconazole Without Corneal De-epithelialization
Topical Natamycin With Corneal De-epithelialization
Topical Natamycin Without Corneal De-epithelialization
Serious adverse events
| Measure |
Topical Voriconazole With Corneal De-epithelialization
n=30 participants at risk
Drug: Voriconazole Voriconazole prepared as a 1% solution. One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Voriconazole Without Corneal De-epithelialization
n=30 participants at risk
Drug: Voriconazole Voriconazole prepared as a 1% solution. One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin With Corneal De-epithelialization
n=30 participants at risk
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Natamycin Without Corneal De-epithelialization
n=30 participants at risk
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|---|---|
|
Eye disorders
Corneal perforation
|
16.7%
5/30 • Number of events 5
|
16.7%
5/30 • Number of events 5
|
26.7%
8/30 • Number of events 8
|
3.3%
1/30 • Number of events 1
|
|
General disorders
Death
|
3.3%
1/30 • Number of events 1
|
0.00%
0/30
|
0.00%
0/30
|
0.00%
0/30
|
Other adverse events
| Measure |
Topical Voriconazole With Corneal De-epithelialization
n=30 participants at risk
Drug: Voriconazole Voriconazole prepared as a 1% solution. One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Voriconazole Without Corneal De-epithelialization
n=30 participants at risk
Drug: Voriconazole Voriconazole prepared as a 1% solution. One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
Topical Natamycin With Corneal De-epithelialization
n=30 participants at risk
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
Procedure/Surgery: Corneal de-epithelialization Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
Topical Natamycin Without Corneal De-epithelialization
n=30 participants at risk
Drug: Natamycin 5% One drop of medication every one hour while awake for one week. For another 2 weeks, one drop of medication every 2 hours while awake.
|
|---|---|---|---|---|
|
Eye disorders
Local allergic reaction
|
0.00%
0/30
|
3.3%
1/30 • Number of events 1
|
0.00%
0/30
|
0.00%
0/30
|
|
Eye disorders
Increase in hypopyon
|
0.00%
0/30
|
6.7%
2/30 • Number of events 2
|
0.00%
0/30
|
3.3%
1/30 • Number of events 1
|
|
Eye disorders
Increase in infiltrate
|
3.3%
1/30 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
|
Eye disorders
No resolution of epithelial defect by 21 days
|
0.00%
0/30
|
0.00%
0/30
|
3.3%
1/30 • Number of events 1
|
0.00%
0/30
|
|
Eye disorders
Progressive corneal thinning
|
3.3%
1/30 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
0.00%
0/30
|
0.00%
0/30
|
Additional Information
Tom M/ Lietman
University of California San Francisco Proctor Foundation
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place