Steroids and Cross-linking for Ulcer Treatment

NCT04097730 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: 18-26045UG1EY028518
• Study Type: interventional
• Target: 280
• Locations: 2 countries
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• Best Spectacle-Corrected Visual Acuity

  Best Spectacle-Corrected Visual Acuity

  6 Months

Secondary Outcomes (5)

• Best Spectacle-Corrected Visual Acuity

  3 Weeks, 3 Months, 12 Months

• Number of Ulcers Testing Positive for Bacteria on Repeat Culture

  2 Days

• Scar Size

  3 Weeks, 3 Months, 6 Months 12 Months

• Scar Depth

  3 Weeks, 3 Months, 6 Months, 12 Months

• Adverse Events

  12 Months

Study Arms (3)

Standard Therapy

PLACEBO COMPARATOR

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

Drug: Moxifloxacin Ophthalmic; Drug: Riboflavin Ophthalmic; Other: Topical Placebo

Early Steroids

EXPERIMENTAL

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

Drug: Moxifloxacin Ophthalmic; Drug: Difluprednate Ophthalmic

Cross-Linking plus Early Steroids

EXPERIMENTAL

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

Drug: Moxifloxacin Ophthalmic; Drug: Difluprednate Ophthalmic; Drug: Riboflavin Ophthalmic

Interventions

Moxifloxacin Ophthalmic 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.

Cross-Linking plus Early Steroids; Early Steroids; Standard Therapy

Difluprednate Ophthalmic 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; Early Steroids

Riboflavin Ophthalmic 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.

Also known as: Corneal Cross-Linking with Riboflavin Ophthalmic

Cross-Linking plus Early Steroids; Standard Therapy

Topical Placebo 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.

Standard Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas M. Lietman: lead
• Aravind Eye Care System: collaborator
• National Eye Institute (NEI): collaborator
• University of Miami: collaborator
• Stanford University: collaborator

Study Sites (3)

Francis I. Proctor Foundaiton

San Francisco, California, 94143, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Aravind Eye Care System

Madurai, Tamil Nadu, India

Location

Related Publications (3)

• 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.

  PMID: 40705354 DERIVED

• 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.

  PMID: 38112645 DERIVED

• 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.

  PMID: 34901464 DERIVED

MeSH Terms

Interventions

Corneal Cross-Linking

Intervention Hierarchy (Ancestors)

Photochemotherapy; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Study Officials

• Tom Lietman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Jennifer Rose-Nussbaumer, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Nicole Varnado, MPH

  Stanford University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 20, 2019
• Study Start: September 24, 2020
• Primary Completion: May 18, 2024
• Study Completion: September 18, 2024
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); US (2)