Steroids and Cross-linking for Ulcer Treatment

NCT ID: NCT04097730

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-24
• Study Completion Date: 2024-09-18

Brief Summary

Steroids and Cross-linking for Ulcer Treatment (SCUT II) is an international, randomized, double-masked, clinical trial. The purpose of this study is to determine differences in 6-month visual acuity between medical antimicrobial treatments alone versus antimicrobial treatment plus collagen cross-linking (CXL), as well as to further evaluate findings from subgroup analyses of SCUT. Patients presenting to the Aravind Eye Care System (India), Kaiser Permanente Northern California (USA), or the University of California, San Francisco (USA) with smear-positive and/or culture-positive typical (i.e. non-Nocardia or Mycobacteria) bacterial corneal ulcers and moderate to severe vision loss, defined as Snellen visual acuity of 20/40 or worse, will be eligible for inclusion. Those who agree to participate will be randomized to one of three treatment groups:

Group 1: Standard therapy, topical 0.5% moxifloxacin plus topical placebo plus sham CXL Group 2: Early steroids, topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus sham CXL Group 3: CXL plus early steroids, topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus CXL

Conditions

Keratitis Bacterial

Study Design

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

Study Groups

Standard Therapy

Participants in this arm will receive topical 0.5% moxifloxacin plus topical placebo plus sham corneal cross-linking.

Group Type: PLACEBO_COMPARATOR

Moxifloxacin Ophthalmic

Intervention Type: DRUG

Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is standard therapy for bacterial keratitis. Immediately after CXL/sham CXL and repeat culture, all participants will receive topical moxifloxacin drops every 1 hour for 2 days, and then every 2 hours while awake until resolution of the epithelial defect.

Riboflavin Ophthalmic

Intervention Type: DRUG

All participants will receive a 30 minute loading dose of topical 0.1% riboflavin and 20% dextran T500 drops every 2 minutes. For participants randomized to corneal cross-linking(CXL), this will be followed by exposure to UV-A light at a wavelength of 365 nm with an irradiance of 3 mW/cm2 for 30 minutes for a total dose of 5.4 J/cm2 (UV lamp: PESCHKE Meditrade GmbH, Hueneberg, Switzerland for India; Avedro KXL System, Waltham, MA, USA for USA). During irradiation patients will continue to receive topical riboflavin at 5-minute intervals. For those randomized to sham CXL, this experience is simulated however the light will be shined adjacent to the patient, careful to avoid exposure to the cornea.

Topical Placebo

Intervention Type: OTHER

Participants randomized to topical placebo will receive topical placebo on the same medication schedule as difluprednate: one drop of 0.05% difluprednate four times daily beginning 24 hours after the initiation of antibiotics for 1 week, decreased by 1 drop weekly for a total of 4 weeks of placebo therapy. Placebo will be the vehicle used in difluprednate.

Early Steroids

Participants in this arm will receive topical 0.5% moxifloxacin plus topical steroids plus sham corneal cross-linking.

Group Type: EXPERIMENTAL

Moxifloxacin Ophthalmic

Intervention Type: DRUG

Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is standard therapy for bacterial keratitis. Immediately after CXL/sham CXL and repeat culture, all participants will receive topical moxifloxacin drops every 1 hour for 2 days, and then every 2 hours while awake until resolution of the epithelial defect.

Difluprednate Ophthalmic

Intervention Type: DRUG

Difluprednate 0.05% is a corticosteroid used to reduce inflammation in the eye. Participants will receive one drop of 0.05% difluprednate four times daily beginning 24 hours after the initiation of antibiotics for 1 week, decreased by 1 drop weekly for a total of 4 weeks of steroid therapy.

Cross-Linking plus Early Steroids

Participants in this group will receive topical 0.5% moxifloxacin plus topical steroids plus corneal cross-linking.

Group Type: EXPERIMENTAL

Moxifloxacin Ophthalmic

Intervention Type: DRUG

Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is standard therapy for bacterial keratitis. Immediately after CXL/sham CXL and repeat culture, all participants will receive topical moxifloxacin drops every 1 hour for 2 days, and then every 2 hours while awake until resolution of the epithelial defect.

Difluprednate Ophthalmic

Intervention Type: DRUG

Difluprednate 0.05% is a corticosteroid used to reduce inflammation in the eye. Participants will receive one drop of 0.05% difluprednate four times daily beginning 24 hours after the initiation of antibiotics for 1 week, decreased by 1 drop weekly for a total of 4 weeks of steroid therapy.

Riboflavin Ophthalmic

Intervention Type: DRUG

All participants will receive a 30 minute loading dose of topical 0.1% riboflavin and 20% dextran T500 drops every 2 minutes. For participants randomized to corneal cross-linking(CXL), this will be followed by exposure to UV-A light at a wavelength of 365 nm with an irradiance of 3 mW/cm2 for 30 minutes for a total dose of 5.4 J/cm2 (UV lamp: PESCHKE Meditrade GmbH, Hueneberg, Switzerland for India; Avedro KXL System, Waltham, MA, USA for USA). During irradiation patients will continue to receive topical riboflavin at 5-minute intervals. For those randomized to sham CXL, this experience is simulated however the light will be shined adjacent to the patient, careful to avoid exposure to the cornea.

Interventions

Moxifloxacin Ophthalmic

Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is standard therapy for bacterial keratitis. Immediately after CXL/sham CXL and repeat culture, all participants will receive topical moxifloxacin drops every 1 hour for 2 days, and then every 2 hours while awake until resolution of the epithelial defect.

Intervention Type: DRUG

Difluprednate Ophthalmic

Difluprednate 0.05% is a corticosteroid used to reduce inflammation in the eye. Participants will receive one drop of 0.05% difluprednate four times daily beginning 24 hours after the initiation of antibiotics for 1 week, decreased by 1 drop weekly for a total of 4 weeks of steroid therapy.

Intervention Type: DRUG

Riboflavin Ophthalmic

All participants will receive a 30 minute loading dose of topical 0.1% riboflavin and 20% dextran T500 drops every 2 minutes. For participants randomized to corneal cross-linking(CXL), this will be followed by exposure to UV-A light at a wavelength of 365 nm with an irradiance of 3 mW/cm2 for 30 minutes for a total dose of 5.4 J/cm2 (UV lamp: PESCHKE Meditrade GmbH, Hueneberg, Switzerland for India; Avedro KXL System, Waltham, MA, USA for USA). During irradiation patients will continue to receive topical riboflavin at 5-minute intervals. For those randomized to sham CXL, this experience is simulated however the light will be shined adjacent to the patient, careful to avoid exposure to the cornea.

Intervention Type: DRUG

Topical Placebo

Participants randomized to topical placebo will receive topical placebo on the same medication schedule as difluprednate: one drop of 0.05% difluprednate four times daily beginning 24 hours after the initiation of antibiotics for 1 week, decreased by 1 drop weekly for a total of 4 weeks of placebo therapy. Placebo will be the vehicle used in difluprednate.

Intervention Type: OTHER

Other Intervention Names

Corneal Cross-Linking with Riboflavin Ophthalmic

Eligibility Criteria

Inclusion Criteria

• Corneal ulcer that is smear positive and/or culture positive (within 24 hours) for typical bacteria (i.e. non-Nocardia or Mycobacteria)
• Moderate to severe vision loss, defined as Snellen visual acuity of 20/40 (6/12) or worse
• Corneal thickness ≥350 µm, as measured on AS-OCT
• Age over 18 years
• Basic understanding of the study as determined by the physician
• Commitment to return for follow up visits

Exclusion Criteria

• Evidence of concomitant infection on exam, gram stain, or confocal microscopy (i.e. herpes, both bacteria and acanthameoba on gram stain)
• Impending or frank perforation at recruitment
• Involvement of sclera at presentation
• Non-infectious or autoimmune keratitis
• History of corneal transplantation or recent intraocular surgery
• Pinhole visual acuity worse than 20/200 in the unaffected eye
• Participants who are decisionally and/or cognitively impaired

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aravind Eye Care System

OTHER

Sponsor Role: collaborator

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Thomas M. Lietman

OTHER

Sponsor Role: lead

Responsible Party

Thomas M. Lietman

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Tom Lietman, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Jennifer Rose-Nussbaumer, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Nicole Varnado, MPH

Role: STUDY_DIRECTOR

Stanford University

Locations

Francis I. Proctor Foundaiton

San Francisco, California, United States

University of Miami

Miami, Florida, United States

Aravind Eye Care System

Madurai, Tamil Nadu, India

Countries

United States; India

References

Prajna NV, Lalitha P, Chandru S, Radhakrishnan N, Christy J, Karthikeyan A, Rajaraman R, Ramesh R, Amescua G, Mandlik K, Abdelrahman S, Varnado N, Kanchugantla M, Arnold B, Lietman TM, Rose-Nussbaumer JR. Steroids and Cross-Linking for Ulcer Treatment: The SCUT II Randomized Clinical Trial. JAMA Ophthalmol. 2025 Jul 24;143(9):723-30. doi: 10.1001/jamaophthalmol.2025.2188. Online ahead of print.

Reference Type: DERIVED

PMID: 40705354 (View on PubMed)

Keenan JD. Steroids in the Management of Infectious Keratitis. Cornea. 2023 Nov 1;42(11):1333-1339. doi: 10.1097/ICO.0000000000003340. Epub 2023 Jul 4.

Reference Type: DERIVED

PMID: 38112645 (View on PubMed)

Radhakrishnan N, Prajna VN, Prajna LS, Venugopal A, Narayana S, Rajaraman R, Amescua G, Porco TC, Lietman TM, Rose-Nussbaumer J. Double-masked, sham and placebo-controlled trial of corneal cross-linking and topical difluprednate in the treatment of bacterial keratitis: Steroids and Cross-linking for Ulcer Treatment Trial (SCUT II) study protocol. BMJ Open Ophthalmol. 2021 Nov 29;6(1):e000811. doi: 10.1136/bmjophth-2021-000811. eCollection 2021.

Reference Type: DERIVED

PMID: 34901464 (View on PubMed)

Other Identifiers

UG1EY028518

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-26045

Identifier Type: -

Identifier Source: org_study_id