Steroids for Corneal Ulcers Trial

NCT ID: NCT00324168

Last Updated: 2018-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2012-12-31

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.

Conditions

Corneal Ulcer; Eye Infections, Bacterial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Antibiotics

Intervention Type: DRUG

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

Topical corticosteroid

Intervention Type: DRUG

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

2

Group Type: PLACEBO_COMPARATOR

Antibiotics

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Interventions

Antibiotics

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Vigamox

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aravind Eye Hospitals, India

OTHER

Sponsor Role: collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: collaborator

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

Thomas M. Lietman

OTHER

Sponsor Role: lead

Responsible Party

Thomas M. Lietman

Prinicpal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

M. Srinivasan, M.S., O.D.

Role: PRINCIPAL_INVESTIGATOR

Aravind Eye Hospital

Mike Zegans, M.D.

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Nisha Acharya, M.D., M.S.

Role: PRINCIPAL_INVESTIGATOR

Proctor Foundation, UCSF

Thomas M Lietman, M.D.

Role: STUDY_DIRECTOR

Proctor Foundation, UCSF

Locations

Proctor Foundation, UCSF

San Francisco, California, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Aravind Eye Hospital

Coimbatore, Tamil Nadu, India

Aravind Eye Hospital

Madurai, Tamil Nadu, India

Aravind Eye Hospital

Tirunelveli, Tamil Nadu, India

Countries

United States; India

References

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.

Reference Type: BACKGROUND

PMID: 21987581 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21987582 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27631025 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24618327 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24612976 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24315294 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23385795 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23307105 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22959881 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22447793 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22395880 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22159005 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 18829631 (View on PubMed)

Other Identifiers

U10EY015114-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H9332-21899-05

Identifier Type: -

Identifier Source: org_study_id