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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
First received
Last updated
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
Health authority
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

Study Design


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
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