Steroids for Corneal Ulcers Trial (SCUT)

July 6, 2018 updated by: Thomas M. Lietman
The purpose of this study is to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers, especially visual acuity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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.

Study Type

Interventional

Enrollment (Actual)

500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Tamil Nadu
      • Coimbatore, Tamil Nadu, India
        • Aravind Eye Hospital
      • Madurai, Tamil Nadu, India, 625 020
        • Aravind Eye Hospital
      • Tirunelveli, Tamil Nadu, India
        • Aravind Eye Hospital
  • United States
    • California
      • San Francisco, California, United States, 94143
        • Proctor Foundation, UCSF
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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
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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment
Time Frame: 3 months from enrollment
3 months from enrollment
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
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
Time to Resolution of Epithelial Defect
Time Frame: 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.
From enrollment up to 21 days
Ocular Perforations
Time Frame: At the time of perforation
At the time of perforation
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
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
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate
Time Frame: 3 months after enrollment
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
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism
Time Frame: 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.
3 months after enrollment
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group
Time Frame: 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
3 months from enrollment
Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth
Time Frame: 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.
3 months from enrollment
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size
Time Frame: 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
3 months from enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas M. Lietman

Collaborators

National Eye Institute (NEI)
Dartmouth-Hitchcock Medical Center
Aravind Eye Hospitals, India

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (ACTUAL)

February 1, 2011

Study Completion (ACTUAL)

December 1, 2012

Study Registration Dates

First Submitted

May 5, 2006

First Submitted That Met QC Criteria

May 5, 2006

First Posted (ESTIMATE)

May 10, 2006

Study Record Updates

Last Update Posted (ACTUAL)

August 1, 2018

Last Update Submitted That Met QC Criteria

July 6, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H9332-21899-05
  • U10EY015114-01 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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