Keratitis BacterialPhase 3SCUT IINCT04097730
Steroids and Cross-linking for Ulcer Treatment
A Phase 3 study testing Moxifloxacin Ophthalmic, Difluprednate Ophthalmic and Riboflavin Ophthalmic in people with Keratitis Bacterial, run by Thomas M. Lietman at 3 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Keratitis Bacterial
- What is being tested?
- Moxifloxacin Ophthalmic, Difluprednate Ophthalmic and Riboflavin Ophthalmic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 24 Sep 2020to 18 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
University of Miami
Miami, Florida, 33136
Francis I. Proctor Foundaiton
San Francisco, California, 94143
About this study
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
- Being tested
- Moxifloxacin Ophthalmic, Difluprednate Ophthalmic, Riboflavin Ophthalmic, Topical Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moxifloxacin OphthalmicDrug
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 OphthalmicDrug
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 OphthalmicDrug
Also called Corneal Cross-Linking with 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.
Topical PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard Therapy | Placebo comparator | Participants in this arm will receive topical 0.5% moxifloxacin plus topical placebo plus sham corneal cross-linking. Receives: 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. Receives: 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. Receives: Drug: Moxifloxacin Ophthalmic; Drug: Difluprednate Ophthalmic; Drug: Riboflavin Ophthalmic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Spectacle-Corrected Visual Acuity
Best Spectacle-Corrected Visual Acuity
Measured: 6 Months
Secondary outcomes (5)
Best Spectacle-Corrected Visual Acuity
Best Spectacle-Corrected Visual Acuity
Measured: 3 Weeks, 3 Months, 12 Months
Number of Ulcers Testing Positive for Bacteria on Repeat Culture
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
Measured: 2 Days
Scar Size
Geometric Mean
Measured: 3 Weeks, 3 Months, 6 Months 12 Months
Scar Depth
Geometric Mean
Measured: 3 Weeks, 3 Months, 6 Months, 12 Months
Adverse Events
Adverse Events
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2019
- Study start24 Sep 2020
- Primary completion18 May 2024
- Study completion18 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Keratitis BacterialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas M. Lietman
- Sponsor type
- University, hospital or other
- Collaborators
- Aravind Eye Care System, National Eye Institute (NEI), University of Miami, Stanford University
- Responsible party
- Sponsor-investigator, Thomas M. Lietman, University of California, San Francisco
- Investigators
- Tom Lietman, MD, Principal investigator, University of California, San FranciscoJennifer Rose-Nussbaumer, MD, Principal investigator, Stanford UniversityNicole Varnado, MPH, Study director, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04097730
- Sponsor's protocol ID
- 18-26045
- Other IDs
- UG1EY028518
- Acronym
- SCUT II
- Status last verified
- Jan 2025
- First submitted
- 12 Sep 2019
- Last updated
- 3 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40705354Keenan 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.
PubMed 38112645Radhakrishnan 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.
PubMed 34901464
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Steroids and Cross-linking for Ulcer Treatment
- ClinicalTrials.gov ID
- NCT04097730
- Acronym / sponsor ID
- SCUT II / 18-26045
- Conditions
- Keratitis Bacterial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Thomas M. LietmanUniversity, hospital or other
- Collaborators
- Aravind Eye Care System, National Eye Institute (NEI), University of Miami, Stanford University
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 18 May 2024 (actual)
- Study completion
- 18 Sep 2024 (actual)
- First posted
- 20 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard Therapy | Placebo comparator | Drug: Moxifloxacin Ophthalmic, Drug: Riboflavin Ophthalmic, Other: Topical PlaceboParticipants in this arm will receive topical 0.5% moxifloxacin plus topical placebo plus sham corneal cross-linking. |
| Early Steroids | Experimental | Drug: Moxifloxacin Ophthalmic, Drug: Difluprednate OphthalmicParticipants in this arm will receive topical 0.5% moxifloxacin plus topical steroids plus sham corneal cross-linking. |
| Cross-Linking plus Early Steroids | Experimental | Drug: Moxifloxacin Ophthalmic, Drug: Difluprednate Ophthalmic, Drug: Riboflavin OphthalmicParticipants in this group will receive topical 0.5% moxifloxacin plus topical steroids plus corneal cross-linking. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Moxifloxacin OphthalmicTopical 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 | Cross-Linking plus Early Steroids, Early Steroids, Standard Therapy |
| Difluprednate OphthalmicDifluprednate 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 | Cross-Linking plus Early Steroids, Early Steroids |
| Riboflavin OphthalmicAlso: Corneal Cross-Linking with Riboflavin OphthalmicAll 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. | Drug | Cross-Linking plus Early Steroids, Standard Therapy |
| Topical PlaceboParticipants 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. | Other | Standard Therapy |
Primary outcome
Best Spectacle-Corrected Visual Acuity
Time frame: 6 Months
Best Spectacle-Corrected Visual Acuity
5 secondary outcomes
Best Spectacle-Corrected Visual Acuity
Time frame: 3 Weeks, 3 Months, 12 Months
Number of Ulcers Testing Positive for Bacteria on Repeat Culture
Time frame: 2 Days
Scar Size
Time frame: 3 Weeks, 3 Months, 6 Months 12 Months
Scar Depth
Time frame: 3 Weeks, 3 Months, 6 Months, 12 Months
Adverse Events
Time frame: 12 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- Derived from this study: PubMed 40705354Prajna 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.
- Derived from this study: PubMed 38112645Keenan 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.
- Derived from this study: PubMed 34901464Radhakrishnan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom Lietman, MD principal investigator
University of California, San Francisco
Jennifer Rose-Nussbaumer, MD principal investigator
Stanford University
Nicole Varnado, MPH study director
Stanford University
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Moxifloxacin Ophthalmic, Difluprednate Ophthalmic and Riboflavin Ophthalmic in people with Keratitis Bacterial, run by Thomas M. Lietman at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Spectacle-Corrected Visual Acuity (time frame: 6 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04097730, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.