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Steroids for Corneal Ulcers Trial (SCUT)

Primary Purpose

Corneal Ulcer, Eye Infections, Bacterial

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Antibiotics
Topical corticosteroid
Placebo
Sponsored by
Thomas M. Lietman
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corneal Ulcer focused on measuring Bacterial Infections, Eye Diseases, Bacterial Keratitis, Visual Acuity

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Proctor Foundation, UCSF
  • Dartmouth Hitchcock Medical Center
  • Aravind Eye Hospital
  • Aravind Eye Hospital
  • Aravind Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

Outcomes

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
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
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.
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.
Ocular Perforations
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.
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.
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.
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
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.
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

Full Information

First Posted
May 5, 2006
Last Updated
July 6, 2018
Sponsor
Thomas M. Lietman
Collaborators
Aravind Eye Hospitals, India, Dartmouth-Hitchcock Medical Center, National Eye Institute (NEI)
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1. Study Identification

Unique Protocol Identification Number
NCT00324168
Brief Title
Steroids for Corneal Ulcers Trial
Acronym
SCUT
Official Title
Steroids for Corneal Ulcers Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas M. Lietman
Collaborators
Aravind Eye Hospitals, India, Dartmouth-Hitchcock Medical Center, National Eye Institute (NEI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Ulcer, Eye Infections, Bacterial
Keywords
Bacterial Infections, Eye Diseases, Bacterial Keratitis, Visual Acuity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
500 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Antibiotics
Other Intervention Name(s)
Vigamox
Intervention Description
moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Intervention Type
Drug
Intervention Name(s)
Topical corticosteroid
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate
Description
LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.
Time Frame
3 months from enrollment
Secondary Outcome Measure Information:
Title
Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment
Time Frame
3 months from enrollment
Title
Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment
Description
LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.
Time Frame
3 months from enrollment
Title
Time to Resolution of Epithelial Defect
Description
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.
Time Frame
From enrollment up to 21 days
Title
Ocular Perforations
Time Frame
At the time of perforation
Title
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate
Description
LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.
Time Frame
12 months from enrollment
Title
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate
Description
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.
Time Frame
3 months after enrollment
Title
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism
Description
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.
Time Frame
3 months after enrollment
Title
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group
Description
Best spectacle-corrected visual acuity (BSCVA) for this subgroup analysis was measured in logMAR and then categorized by equivalent Snellen fractions
Time Frame
3 months from enrollment
Title
Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth
Description
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.
Time Frame
3 months from enrollment
Title
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size
Description
Best-spectacle visual acuity (BSCVA) at 3 months from enrollment is stratified by categories of infiltrate/scar size and examined by treatment arm
Time Frame
3 months from enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M. Srinivasan, M.S., O.D.
Organizational Affiliation
Aravind Eye Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mike Zegans, M.D.
Organizational Affiliation
Dartmouth-Hitchcock Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nisha Acharya, M.D., M.S.
Organizational Affiliation
Proctor Foundation, UCSF
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas M Lietman, M.D.
Organizational Affiliation
Proctor Foundation, UCSF
Official's Role
Study Director
Facility Information:
Facility Name
Proctor Foundation, UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Aravind Eye Hospital
City
Coimbatore
State/Province
Tamil Nadu
Country
India
Facility Name
Aravind Eye Hospital
City
Madurai
State/Province
Tamil Nadu
ZIP/Postal Code
625 020
Country
India
Facility Name
Aravind Eye Hospital
City
Tirunelveli
State/Province
Tamil Nadu
Country
India

12. IPD Sharing Statement

Citations:
PubMed Identifier
21987581
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.
Results Reference
background
PubMed Identifier
21987582
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. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50. doi: 10.1001/archophthalmol.2011.315. Epub 2011 Oct 10.
Results Reference
result
PubMed Identifier
27631025
Citation
Hammond JH, Hebert WP, Naimie A, Ray K, Van Gelder RD, DiGiandomenico A, Lalitha P, Srinivasan M, Acharya NR, Lietman T, Hogan DA, Zegans ME. Environmentally Endemic Pseudomonas aeruginosa Strains with Mutations in lasR Are Associated with Increased Disease Severity in Corneal Ulcers. mSphere. 2016 Sep 7;1(5):e00140-16. doi: 10.1128/mSphere.00140-16. eCollection 2016 Sep-Oct.
Results Reference
derived
PubMed Identifier
24618327
Citation
McClintic SM, Prajna NV, Srinivasan M, Mascarenhas J, Lalitha P, Rajaraman R, Oldenburg CE, O'Brien KS, Ray KJ, Acharya NR, Lietman TM, Keenan JD. Visual outcomes in treated bacterial keratitis: four years of prospective follow-up. Invest Ophthalmol Vis Sci. 2014 May 2;55(5):2935-40. doi: 10.1167/iovs.14-13980.
Results Reference
derived
PubMed Identifier
24612976
Citation
Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Ray KJ, Zegans ME, Acharya NR, Lietman TM, Keenan JD; Steroids for Corneal Ulcers Trial Group. Visual recovery in treated bacterial keratitis. Ophthalmology. 2014 Jun;121(6):1310-1. doi: 10.1016/j.ophtha.2013.12.041. Epub 2014 Mar 5.
Results Reference
derived
PubMed Identifier
24315294
Citation
Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, O'Brien KS, Glidden DV, Ray KJ, Oldenburg CE, Zegans ME, Whitcher JP, McLeod SD, Porco TC, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol. 2014 Feb;157(2):327-333.e3. doi: 10.1016/j.ajo.2013.09.025. Epub 2013 Oct 1.
Results Reference
derived
PubMed Identifier
23385795
Citation
Oldenburg CE, Lalitha P, Srinivasan M, Manikandan P, Bharathi MJ, Rajaraman R, Ravindran M, Mascarenhas J, Nardone N, Ray KJ, Glidden DV, Acharya NR, Lietman TM. Moxifloxacin susceptibility mediates the relationship between causative organism and clinical outcome in bacterial keratitis. Invest Ophthalmol Vis Sci. 2013 Feb 28;54(2):1522-6. doi: 10.1167/iovs.12-11246.
Results Reference
derived
PubMed Identifier
23307105
Citation
Ray KJ, Prajna L, Srinivasan M, Geetha M, Karpagam R, Glidden D, Oldenburg CE, Sun CQ, McLeod SD, Acharya NR, Lietman TM. Fluoroquinolone treatment and susceptibility of isolates from bacterial keratitis. JAMA Ophthalmol. 2013 Mar;131(3):310-3. doi: 10.1001/jamaophthalmol.2013.1718.
Results Reference
derived
PubMed Identifier
22959881
Citation
Lalitha P, Srinivasan M, Rajaraman R, Ravindran M, Mascarenhas J, Priya JL, Sy A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Lietman TM, Acharya NR. Nocardia keratitis: clinical course and effect of corticosteroids. Am J Ophthalmol. 2012 Dec;154(6):934-939.e1. doi: 10.1016/j.ajo.2012.06.001. Epub 2012 Sep 5.
Results Reference
derived
PubMed Identifier
22447793
Citation
Lalitha P, Srinivasan M, Manikandan P, Bharathi MJ, Rajaraman R, Ravindran M, Cevallos V, Oldenburg CE, Ray KJ, Toutain-Kidd CM, Glidden DV, Zegans ME, McLeod SD, Acharya NR, Lietman TM. Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis. Clin Infect Dis. 2012 May;54(10):1381-7. doi: 10.1093/cid/cis189. Epub 2012 Mar 23.
Results Reference
derived
PubMed Identifier
22395880
Citation
Dalmon C, Porco TC, Lietman TM, Prajna NV, Prajna L, Das MR, Kumar JA, Mascarenhas J, Margolis TP, Whitcher JP, Jeng BH, Keenan JD, Chan MF, McLeod SD, Acharya NR. The clinical differentiation of bacterial and fungal keratitis: a photographic survey. Invest Ophthalmol Vis Sci. 2012 Apr 2;53(4):1787-91. doi: 10.1167/iovs.11-8478.
Results Reference
derived
PubMed Identifier
22159005
Citation
Sy A, Srinivasan M, Mascarenhas J, Lalitha P, Rajaraman R, Ravindran M, Oldenburg CE, Ray KJ, Glidden D, Zegans ME, McLeod SD, Lietman TM, Acharya NR. Pseudomonas aeruginosa keratitis: outcomes and response to corticosteroid treatment. Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):267-72. doi: 10.1167/iovs.11-7840.
Results Reference
derived
PubMed Identifier
18829631
Citation
Srinivasan M, Lalitha P, Mahalakshmi R, Prajna NV, Mascarenhas J, Chidambaram JD, Lee S, Hong KC, Zegans M, Glidden DV, McLeod S, Whitcher JP, Lietman TM, Acharya NR. Corticosteroids for bacterial corneal ulcers. Br J Ophthalmol. 2009 Feb;93(2):198-202. doi: 10.1136/bjo.2008.147298. Epub 2008 Oct 1.
Results Reference
derived

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Steroids for Corneal Ulcers Trial

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