REAGIR: Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction

Sponsor

Thomas M. Lietman (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05110001

Collaborator

Aravind Eye Care System (Other), National Eye Institute (NEI) (NIH), Stanford University (Other)

330

Enrollment

Location

Arms

Anticipated Duration (Months)

8.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rose Bengal Electromagnetic Activation with Green light for Infection Reduction (REAGIR ) is an international, randomized, doubled 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 cross-linking with rose Bengal (RB-PDT).

Patients presenting to one of the Aravind Eye Hospitals in India with either smear or culture positive fungal or acanthamoeba keratitis or smear and culture negative 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 two treatment groups:

Group 4, Sham RB-PDT: topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus sham RB-PDT

Group 5, RB-PDT: topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus RB-PDT.

Condition or Disease	Intervention/Treatment	Phase
Acanthamoeba Keratitis Fungal Keratitis	Drug: Moxifloxacin Ophthalmic Drug: Chlorhexidine Gluconate Drug: Natamycin Drug: Rose Bengal Other: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

330 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Standard Therapy Patients in this arm will receive topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus sham RB-PDT	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: Chlorhexidine Gluconate Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis. Drug: Natamycin Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. Other: Placebo Study participants receive sham RB-PDT within 48 hours of randomization. Participants will receive a 30-minute loading dose of topical balanced salt solution which will be applied in 5-minute intervals to the de-epithelialized cornea. A pen light covered with a green filter will be used for 15 minutes. Repeat cornea culture will be collected 30 minutes after the sham procedure.
Experimental: Cross-Linking with rose Bengal (RB-PDT) Patients in this arm will receive topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus RB-PDT	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: Chlorhexidine Gluconate Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis. Drug: Natamycin Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal 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 (0.2% RB in BSS) which will be applied in 5-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 30 minutes after the procedure. Other Names: Corneal Cross Linking with rose Bengal

Arm

Intervention/Treatment

Placebo Comparator: Standard Therapy

Patients in this arm will receive topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus sham RB-PDT

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: Chlorhexidine Gluconate

Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis.

Drug: Natamycin

Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis.

Other: Placebo

Study participants receive sham RB-PDT within 48 hours of randomization. Participants will receive a 30-minute loading dose of topical balanced salt solution which will be applied in 5-minute intervals to the de-epithelialized cornea. A pen light covered with a green filter will be used for 15 minutes. Repeat cornea culture will be collected 30 minutes after the sham procedure.

Experimental: Cross-Linking with rose Bengal (RB-PDT)

Patients in this arm will receive topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus RB-PDT

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: Chlorhexidine Gluconate

Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis.

Drug: Natamycin

Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal 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 (0.2% RB in BSS) which will be applied in 5-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 30 minutes after the procedure.

Other Names:

Corneal Cross Linking with rose Bengal

Outcome Measures

Primary Outcome Measures

Best Spectacle-Corrected Visual Acuity [6 Months]
Best Spectacle-Corrected Visual Acuity

Secondary Outcome Measures

Best Spectacle-Corrected Visual Acuity [3 Weeks, 3 Months, 12 Months]
Best Spectacle-Corrected Visual Acuity
Scar Size [3 Weeks, 3 Months, 6 Months 12 Months]
Geometric Mean
Scar Depth [3 Weeks, 3 Months, 6 Months 12 Months]
Geometric Mean
Adverse Events [12 Months]
Adverse Events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Presence of smear or culture positive fungal or acanthamoeba ulcer; smear or culture negative ulcer; or any atypical bacteria (such as Nocardia)
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
Non-infectious or autoimmune keratitis
History of corneal transplantation
History of intraocular surgery within last three months
Pinhole visual acuity worse than 20/200 in the unaffected eye
Participants who are decisionally and/or cognitively impaired
Presence of demestocele at recruitment