Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction II (REAGIR II)

Rose Bengal Electromagnetic Activation with Green light for Infection Reduction II (REAGIR II) is a randomized, double-masked feasibility study. The purpose of this study is to determine differences in 6-month visual acuity between medical antimicrobial treatments alone versus antimicrobial treatment plus cross-linking with rose Bengal (RB-PDT).

Patients presenting to one of the Aravind Eye Hospitals in India or to the Federal University of São Paulo ophthalmology clinic in Brazil 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 of worse, will be eligible for inclusion. Those who agree to participate will be randomized to one of two treatment groups:

• Group 6, RB-PDT Plus Early Steroids: topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus RB-PDT
• Group 7, Sham RB-PDT Plus Early Steroids: topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus sham RB-PDT

Study Overview

• Status: Not yet recruiting
• Conditions: Bacterial Keratitis
• Intervention / Treatment: Drug: Difluprednate Ophthalmic; Drug: Moxifloxacin Ophthalmic; Drug: Rose Bengal

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jennifer Rose-Nussbaumer, MD; Phone Number: 650-402-8820; Email: rosej@stanford.edu
• Study Contact Backup: Name: Thomas Lietman, MD; Phone Number: 415-502-2662; Email: tom.lietman@ucsf.edu

Study Locations

• Brazil
  • São Paulo, Brazil
    • Federal University of São Paulo
    • Contact: Ana Luisa Hofling Lima, MD, PhD; Email: analhofling@gmail.com
• India
  • Tamil Nadu
    • Madurai, Tamil Nadu, India
      • Aravind Eye Care System
      • Contact: N V Prajna; Email: prajna@aravind.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Corneal ulcer that is smear positive and/or culture positive (within 24 hours) for typical bacteria (i.e. non-Nocardia or Myobacteria)
• 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 acanthamoeba on gram stain)
• Impending or frank perforation at recruitment
• Involvement of sclera at presentation
• Presence of desmetocele at recruitment
• Non-infectious or autoimmune keratitis
• History of corneal transplantation
• History of intraocular surgery within the last three months*
• Pinhole visual acuity worse than 20/200 in the unaffected eye
• Participants who are decisionally and/or cognitively impaired

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RB-PDT Plus Early Steroids	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: Moxifloxacin Ophthalmic; Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is a standard therapy for bacterial keratitis.; Drug: Rose Bengal; Study participants receive RB-PDT within 48 hours of randomization. All participants will receive a 30-minute loading dose of topical Rose Bengal (0.1% RB in 0.9% sodium chloride) which will be applied in 3-minute intervals to the de-epithelialized cornea. This will be followed by irradiation with a 6mW/cm2 custom-made green LED source for 15 minutes (5.4J/cm2). Repeat cornea culture will be collected within 24 hours after the procedure.; Other Names: Corneal Cross Linking with rose Bengal
Experimental: Sham RB-PDT Plus Early Steroids	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: Moxifloxacin Ophthalmic; Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is a standard therapy for bacterial keratitis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Spectacle-Corrected Visual Acuity	Best Spectacle-Corrected Visual Acuity	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Spectacle-Corrected Visual Acuity	Best Spectacle-Corrected Visual Acuity	3 Weeks, 3 Months, 12 Months
Adverse Events	Adverse Events	12 Months
Scar size	Geometric mean	3 Weeks, 3 Months, 6 Months 12 Months
Scar depth	Geometric mean	3 Weeks, 3 Months, 6 Months 12 Months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Stanford University; Federal University of São Paulo; Aravind Eye Care System
• Investigators: Principal Investigator: Jennifer Rose-Nussbaumer, MD, Stanford University; Study Director: Nicole Varnado, MPH, Stanford University; Principal Investigator: Thomas Lietman, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Estimated): February 22, 2024

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin; Difluprednate
• Other Study ID Numbers: 18-26045-RII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No