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Steroids and Cross-linking for Ulcer Treatment (SCUT II)

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ClinicalTrials.gov Identifier: NCT04097730
Recruitment Status : Not yet recruiting
First Posted : September 20, 2019
Last Update Posted : September 20, 2019
Sponsor:
Collaborators:
Kaiser Permanente
Aravind Eye Care System
National Eye Institute (NEI)
Information provided by (Responsible Party):
Thomas M. Lietman, University of California, San Francisco

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 3-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 in India, to Kaiser Permanente Northern California 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 20/60 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


Condition or disease Intervention/treatment Phase
Keratitis Fungal Drug: Moxifloxacin Ophthalmic Drug: Difluprednate Ophthalmic Drug: Riboflavin Ophthalmic Other: Topical Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 273 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Steroids and Cross-linking for Ulcer Treatment
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Riboflavin

Arm Intervention/treatment
Placebo Comparator: Standard Therapy
Participants in this arm will receive topical 0.5% moxifloxacin plus topical placebo plus sham corneal cross-linking.
Drug: 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.

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. The patient's cornea will be completely covered with a corneal sponge to further prevent exposure.
Other Name: Corneal Cross-Linking with Riboflavin Ophthalmic

Other: 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.

Experimental: Early Steroids
Participants in this arm will receive topical 0.5% moxifloxacin plus topical steroids plus sham corneal cross-linking.
Drug: 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.

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.

Experimental: Cross-Linking plus Early Steroids
Participants in this group will receive topical 0.5% moxifloxacin plus topical steroids plus corneal cross-linking.
Drug: 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.

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.

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. The patient's cornea will be completely covered with a corneal sponge to further prevent exposure.
Other Name: Corneal Cross-Linking with Riboflavin Ophthalmic




Primary Outcome Measures :
  1. Best Spectacle-Corrected Visual Acuity [ Time Frame: 3 Months ]
    Best Spectacle-Corrected Visual Acuity


Secondary Outcome Measures :
  1. Best Spectacle-Corrected Visual Acuity [ Time Frame: 12 Months ]
    Best Spectacle-Corrected Visual Acuity

  2. Number of Ulcers Testing Positive for Bacteria on Repeat Culture [ Time Frame: 2 Days ]
    Microbiological cure on repeat culture: A scraping of the corneal ulcer taken at 48 hours, then swabbed onto a culture plate and assessed for bacteria

  3. Scar Size [ Time Frame: 3 Weeks, 3 Months, 12 Months ]
    Geometric Mean

  4. Scar Depth [ Time Frame: 3 Weeks, 3 Months, 12 Months ]
    Geometric Mean

  5. Adverse Events [ Time Frame: 12 Months ]
    Adverse Events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 20/60 (6/18) or worse
  • Corneal thickness ≥300 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04097730


Contacts
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Contact: Tom Lietman, MD 415-502-2662 tom.lietman@ucsf.edu
Contact: Ariana Austin, MS 415-502-0275 ariana.austin@ucsf.edu

Locations
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United States, California
Kaiser Permanente Northern California Not yet recruiting
Redwood City, California, United States, 94063
Contact: Jennifer Rose-Nussbaumer, MD    650-299-2111    jennifer.rose-nussbaumer@kp.org   
Francis I. Proctor Foundaiton Not yet recruiting
San Francisco, California, United States, 94143
Contact: Tom Lietman, MD    415-502-2662    tom.lietman@ucsf.edu   
Contact: Ariana Austin, MS    415-502-0275    ariana.austin@ucsf.edu   
India
Aravind Eye Care System Not yet recruiting
Madurai, Tamil Nadu, India
Contact: N.V. Prajna       prajna@aravind.org   
Sponsors and Collaborators
Thomas M. Lietman
Kaiser Permanente
Aravind Eye Care System
National Eye Institute (NEI)
Investigators
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Principal Investigator: Tom Lietman, MD University of California, San Francisco
Principal Investigator: Jennifer Rose-Nussbaumer, MD Kaiser Permanente
Study Director: Ariana Austin, MS University of California, San Francisco

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Responsible Party: Thomas M. Lietman, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04097730     History of Changes
Other Study ID Numbers: 18-26045
UG1EY028518 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Keratitis
Corneal Diseases
Eye Diseases
Riboflavin
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Difluprednate
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Photosensitizing Agents
Dermatologic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists