Trial Outcomes & Findings for Steroids for Corneal Ulcers Trial (NCT NCT00324168)

NCT ID: NCT00324168

Last Updated: 2018-08-01

Results Overview

LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 500 participants
• Primary outcome timeframe: 3 months from enrollment
• Results posted on: 2018-08-01

Participant Flow

Between September 1, 2006 and February 22, 2010, 1,769 patients were screened for the trial and 500 patients were enrolled.

Common reasons for ineligibility include impending perforation (n=316, 25%), history of a corneal scar in the affected eye (n=123, 10%) and vision worse than 6/60 in the fellow eye (n=119, 9%).

Participant milestones

Measure	Steroid Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Overall Study STARTED	250	250
Overall Study COMPLETED	222	220
Overall Study NOT COMPLETED	28	30

Reasons for withdrawal

Measure	Steroid Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Overall Study Lost to Follow-up	19	18
Overall Study Death	3	3
Overall Study Patient did not visit in f/u window	6	9

Baseline Characteristics

Steroids for Corneal Ulcers Trial

Baseline characteristics by cohort

Measure	Steroid n=250 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=250 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Total n=500 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	190 Participants n=5 Participants	198 Participants n=7 Participants	388 Participants n=5 Participants
Age, Categorical >=65 years	56 Participants n=5 Participants	49 Participants n=7 Participants	105 Participants n=5 Participants
Age, Continuous	52.0 years n=5 Participants	54.5 years n=7 Participants	53.0 years n=5 Participants
Sex: Female, Male Female	124 Participants n=5 Participants	103 Participants n=7 Participants	227 Participants n=5 Participants
Sex: Female, Male Male	126 Participants n=5 Participants	147 Participants n=7 Participants	273 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment India	243 participants n=5 Participants	242 participants n=7 Participants	485 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months from enrollment

LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate	0.48 logMAR Interval 0.42 to 0.53	0.49 logMAR Interval 0.43 to 0.54

SECONDARY outcome

Timeframe: 3 months from enrollment

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment	3.07 mm Interval 2.99 to 3.16	3.02 mm Interval 2.93 to 3.11

SECONDARY outcome

Timeframe: 3 months from enrollment

LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment	0.42 logMAR Interval 0.36 to 0.47	0.41 logMAR Interval 0.36 to 0.46

SECONDARY outcome

Timeframe: From enrollment up to 21 days

This outcome measured time from enrollment to resolution of the epithelial defect in days for up to 21 days. For three weeks patients were examined every 3 days for size of epithelial defect until the defect was gone.

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Time to Resolution of Epithelial Defect	9.77 days Standard Deviation 7.54 • Interval 7.54 to	9.43 days Standard Deviation 7.10

SECONDARY outcome

Timeframe: At the time of perforation

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Ocular Perforations	7 participants	8 participants

SECONDARY outcome

Timeframe: 12 months from enrollment

LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate	2.90 logMAR Interval 2.8 to 3.01	2.87 logMAR Interval 2.77 to 2.98

SECONDARY outcome

Timeframe: 3 months after enrollment

Population: The study population analyzed for this outcome includes only those study subjects for whom an MIC value was available.

Best spectacle-corrected visual acuity (BSCVA) for this outcome is measured in logMAR (logarithm of the Minimum Angle of Resolution) in which smaller values indicate better visual acuity. Minimum inhibitory concentration (MIC) to moxifloxacin was measured by E test and a log2-transformation of MIC was used in all analyses. In this analysis we add MIC to the model examining BSCVA at 3 months.

Outcome measures

Measure	Steroid n=213 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=218 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate	0.50 logMAR 95% Confidence Interval 0.58 • Interval 0.44 to 0.56	0.46 logMAR 95% Confidence Interval 0.49 • Interval 0.4 to 0.52

SECONDARY outcome

Timeframe: 3 months after enrollment

BSCVA measured in logMAR will be estimated by causative organism (either Nocardia spp, Streptococcus pneumoniae, Moraxella spp, or Pseudomonas aeruginosa). BSCVA will be examined for each causative organism by mean and standard deviation as well as in a regression model.

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism Nocardia spp	0.54 logMAR Standard Deviation 0.67	0.36 logMAR Standard Deviation 0.64
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism Streptococcus pneumoniae	0.49 logMAR Standard Deviation 0.56	0.52 logMAR Standard Deviation 0.53
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism Moraxella spp	0.46 logMAR Standard Deviation 0.61	0.26 logMAR Standard Deviation 0.65
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism Pseudomonas aeruginosa	0.53 logMAR Standard Deviation 0.54	0.45 logMAR Standard Deviation 0.56

SECONDARY outcome

Timeframe: 3 months from enrollment

Best spectacle-corrected visual acuity (BSCVA) for this subgroup analysis was measured in logMAR and then categorized by equivalent Snellen fractions

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group <20/40	0.06 logMAR Standard Deviation 0.30	-0.02 logMAR Standard Deviation 0.12
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group 20/40 to 20/800	0.36 logMAR Standard Deviation 0.43	0.38 logMAR Standard Deviation 0.38
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group Counting fingers (CF) or worse	1.00 logMAR Standard Deviation 0.55	1.15 logMAR Standard Deviation 0.61

SECONDARY outcome

Timeframe: 3 months from enrollment

BSCVA measured in logMAR will be examined by categories infiltrate depth (categorized by depth percentage) by mean and standard deviation as well as in a regression model.

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth >0-33%	0.35 logMAR Standard Deviation 0.50	0.26 logMAR Standard Deviation 0.40
Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth >33%-67%	0.52 logMAR Standard Deviation 0.57	0.47 logMAR Standard Deviation 0.54
Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth >67%-100%	0.80 logMAR Standard Deviation 0.61	0.86 logMAR Standard Deviation 0.67

SECONDARY outcome

Timeframe: 3 months from enrollment

Best-spectacle visual acuity (BSCVA) at 3 months from enrollment is stratified by categories of infiltrate/scar size and examined by treatment arm

Outcome measures

Measure	Steroid n=222 Participants Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=220 Participants Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size 0-1.90 mm	0.18 logMAR Standard Deviation 0.37	0.19 logMAR Standard Deviation 0.33
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size 1.91-2.70 mm	0.39 logMAR Standard Deviation 0.51	0.29 logMAR Standard Deviation 0.44
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size 2.71-4.06 mm	0.53 logMAR Standard Deviation 0.60	0.53 logMAR Standard Deviation 0.53
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size 4.07-8.90 mm	0.85 logMAR Standard Deviation 0.57	0.96 logMAR Standard Deviation 0.67

Adverse Events

Steroid

Serious events: 15 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 13 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	Steroid n=250 participants at risk Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=250 participants at risk Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Eye disorders Corneal perforation	2.8% 7/250 • 3 months from enrollment	3.2% 8/250 • 3 months from enrollment
General disorders Death	2.8% 7/250 • 3 months from enrollment	2.0% 5/250 • 3 months from enrollment
Infections and infestations Systemic infection	0.40% 1/250 • 3 months from enrollment	0.00% 0/250 • 3 months from enrollment

Other adverse events

Measure	Steroid n=250 participants at risk Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo n=250 participants at risk Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Eye disorders Increase in hypopyon	1.6% 4/250 • 3 months from enrollment	1.6% 4/250 • 3 months from enrollment
Eye disorders Increase in infiltrate size >50%	3.6% 9/250 • 3 months from enrollment	1.6% 4/250 • 3 months from enrollment
Eye disorders No healing of epithelial defect by 21 days	17.6% 44/250 • 3 months from enrollment	10.8% 27/250 • 3 months from enrollment
Eye disorders Intraocular pressure (IOP) elevated >25mm Hg by <35 mm Hg	0.80% 2/250 • 3 months from enrollment	4.0% 10/250 • 3 months from enrollment
Eye disorders Progressive corneal thinning	0.00% 0/250 • 3 months from enrollment	0.80% 2/250 • 3 months from enrollment
General disorders Other	3.6% 9/250 • 3 months from enrollment	5.2% 13/250 • 3 months from enrollment

Additional Information

Dr. Thomas Lietman

F.I. Proctor Foundation, University of Califonia, San Francisco

Phone: 415-502-2662

Email: tom.lietman@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place