Steroids for Corneal Ulcers Trial (SCUT)

This study has been completed.
Sponsor:
Collaborators:
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
Information provided by (Responsible Party):
Thomas M. Lietman, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00324168
First received: May 5, 2006
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Corneal Ulcer
Eye Infections, Bacterial
Drug: Antibiotics
Drug: Topical corticosteroid
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Steroids for Corneal Ulcers Trial

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
    LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.


Secondary Outcome Measures:
  • Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
  • Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
    LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

  • Time to Resolution of Epithelial Defect [ Time Frame: From enrollment up to 21 days ] [ Designated as safety issue: No ]
    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.

  • Ocular Perforations [ Time Frame: At the time of perforation ] [ Designated as safety issue: No ]
  • Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate [ Time Frame: 12 months from enrollment ] [ Designated as safety issue: No ]
    LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

  • Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    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.

  • Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    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.

  • Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
    Best spectacle-corrected visual acuity (BSCVA) for this subgroup analysis was measured in logMAR and then categorized by equivalent Snellen fractions

  • Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
    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.

  • Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
    Best-spectacle visual acuity (BSCVA) at 3 months from enrollment is stratified by categories of infiltrate/scar size and examined by treatment arm


Enrollment: 500
Study Start Date: September 2006
Study Completion Date: December 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Antibiotics
moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Other Name: Vigamox
Drug: 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 Comparator: 2 Drug: Antibiotics
moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Other Name: Vigamox
Drug: 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

Detailed 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 corneal 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 were randomized to receive antibiotic plus steroid or antibiotic plus placebo. They were followed closely until re-epithelialization and then rechecked at three weeks, three months and 12 months post enrollment. A subset of patients were 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.

The 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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324168

Locations
United States, California
Proctor Foundation, UCSF
San Francisco, California, United States, 94143
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
India
Aravind Eye Hospital
Coimbatore, Tamil Nadu, India
Aravind Eye Hospital
Madurai, Tamil Nadu, India, 625 020
Aravind Eye Hospital
Tirunelveli, Tamil Nadu, India
Sponsors and Collaborators
Thomas M. Lietman
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: M. Srinivasan, M.S., O.D. Aravind Eye Hospital
Principal Investigator: Mike Zegans, M.D. Dartmouth-Hitchcock Medical Center
Principal Investigator: Nisha Acharya, M.D., M.S. Proctor Foundation, UCSF
Study Director: Thomas M Lietman, M.D. Proctor Foundation, UCSF
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Thomas M. Lietman, Prinicpal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00324168     History of Changes
Other Study ID Numbers: H9332-21899-05, U10-EY015114-01
Study First Received: May 5, 2006
Results First Received: November 29, 2012
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Bacterial Infections
Eye Diseases
Bacterial Keratitis
Visual Acuity

Additional relevant MeSH terms:
Infection
Ulcer
Corneal Ulcer
Bacterial Infections
Eye Infections
Eye Infections, Bacterial
Pathologic Processes
Keratitis
Corneal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 18, 2014