Steroids for Corneal Ulcers Trial

Corneal Ulcer Clinical Trial

— SCUT  

Official title:

Steroids for Corneal Ulcers Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00324168
• Other study ID #: H9332-21899-05
• Secondary ID: U10EY015114-01
• Status: Completed
• Phase: Phase 4
• Start date: September 2006
• Est. completion date: December 2012

Study information

• Verified date: July 2018
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers, especially visual acuity.

Description:

Antimicrobial treatment of a bacterial corneal ulcer is generally effective in eradicating infection. However, "successful" treatment is not always associated with a good visual outcome. The scarring that accompanies the resolution of infection leaves many eyes blind. Some cornea specialists advocate the use of topical corticosteroids along with antibiotics in an effort to reduce immune-mediated tissue damage and scarring. Others fear using steroids to reduce the cornea's immune response will prolong or even exacerbate infection. Ophthalmologists have been divided on this issue for more than 30 years, and both approaches are acceptable according to the American Academy of Ophthalmology's Preferred Practice Patterns. Evidence from animal and human reports is mixed. A single randomized trial saw a non-significant benefit to steroids but was drastically underpowered (20 patients per study arm).

The study is a randomized, double-masked, placebo-controlled trial to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers. Five hundred bacterial corneal ulcers presenting to the Aravind Eye Hospitals, the University of California, San Francisco (UCSF) Proctor Foundation, and the Dartmouth-Hitchcock Medical Center will be randomized to receive antibiotic plus steroid or antibiotic plus placebo. Participants will be followed closely until re-epithelialization and then rechecked at three weeks, three months and 12 months post enrollment. A subset of patients will be contacted for a follow-up visit four years post enrollment. The primary outcome is best spectacle-corrected visual acuity three months after enrollment, using best spectacle-corrected enrollment visual acuity as a co-variate.

A pilot study was conducted from January 2005 to August 2005 at Aravind Eye Hospital to assess the feasibility and safety and to estimate the sample size of a larger main trial. Forty-two patients with culture-proven bacterial keratitis were enrolled. They were treated and followed up as in the main trial, up to three months from enrollment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: December 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria

At Presentation:

• Presence of a corneal ulcer at presentation

At Enrollment:

• Presence of bacteria on blood or chocolate agar culture

• Antibiotic given for > 48 hours

• The patient must be able to verbalize a basic understanding of the study after it is explained to the patient, as determined by physician examiner. This understanding must include a commitment to return for f/u visits.

• Appropriate consent

Exclusion Criteria

At Presentation:

• Overlying epithelial defect < 0.75 mm at its greatest width at presentation

• Corneal perforation or impending perforation

• Evidence of fungus on KOH, Giemsa at time of presentation

• Evidence of acanthamoeba by stain

• Evidence of herpetic keratitis by history or exam

• Corneal scar not easily distinguishable from current ulcer

• Use of a topical steroid in the affected eye during the course of the present ulcer, including use after the symptoms of the ulcer started but before presentation

• Use of systemic prednisolone during the course of the present ulcer

• Age less than 16 years (before 16th birthday)

• Bilateral ulcers

• Previous penetrating keratoplasty

• Pregnancy (by history or urine test)

• Immediate steroid use necessary due to surgery or other condition

At Enrollment:

• Evidence of fungus on culture at time of enrollment

• Absence of bacteria on blood or chocolate agar culture

• Best spectacle-corrected vision worse than 6/60 in the fellow eye

• Corneal perforation or descemetocele

• Known allergy to study medications (steroid or preservative)

• No light perception in the affected eye

• Not willing to come to follow-up visits

• Not willing to participate

Related Conditions & MeSH terms

• Bacterial Infections
• Corneal Ulcer
• Eye Infections
• Eye Infections, Bacterial
• Ulcer

Intervention

Drug:
• Antibiotics
moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
• 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
• 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

Locations

Country	Name	City	State
India	Aravind Eye Hospital	Coimbatore	Tamil Nadu
India	Aravind Eye Hospital	Madurai	Tamil Nadu
India	Aravind Eye Hospital	Tirunelveli	Tamil Nadu
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Proctor Foundation, UCSF	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
Thomas M. Lietman	Aravind Eye Hospitals, India, Dartmouth-Hitchcock Medical Center, National Eye Institute (NEI)

Countries where clinical trial is conducted

United States,  India, 

References & Publications (2)

Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroi — View Citation

Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial: study design and baseline characteristics. Arch Ophthalmol. 2012 Feb;130(2):151-7. doi: 10.1001/archophthalmol.2011.303. Epub 2011 Oct 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate	LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.	3 months from enrollment
Secondary	Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment		3 months from enrollment
Secondary	Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment	LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.	3 months from enrollment
Secondary	Time to Resolution of Epithelial Defect	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.	From enrollment up to 21 days
Secondary	Ocular Perforations		At the time of perforation
Secondary	Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate	LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.	12 months from enrollment
Secondary	Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate	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.	3 months after enrollment
Secondary	Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism	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.	3 months after enrollment
Secondary	Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group	Best spectacle-corrected visual acuity (BSCVA) for this subgroup analysis was measured in logMAR and then categorized by equivalent Snellen fractions	3 months from enrollment
Secondary	Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth	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.	3 months from enrollment
Secondary	Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size	Best-spectacle visual acuity (BSCVA) at 3 months from enrollment is stratified by categories of infiltrate/scar size and examined by treatment arm	3 months from enrollment