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| ID | Type | Description | Link |
|---|---|---|---|
| UG1EY028518 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Aravind Eye Care System | OTHER |
| National Eye Institute (NEI) | NIH |
| Stanford University | OTHER |
| Federal University of São Paulo |
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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 or to the Federal University of São Paulo ophthalmology clinic in Brazil 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Therapy | Placebo Comparator | 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 |
|
| Cross-Linking with rose Bengal (RB-PDT) | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Moxifloxacin Ophthalmic | Drug | Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is a standard therapy for bacterial keratitis. |
| Measure | Description | Time Frame |
|---|---|---|
| Best Spectacle-Corrected Visual Acuity | Best Spectacle-Corrected Visual Acuity | 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Best Spectacle-Corrected Visual Acuity | Best Spectacle-Corrected Visual Acuity | 3 Weeks, 3 Months, 12 Months |
| Scar Size | Geometric Mean |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tom Lietman, MD | University of California, San Frnasco | Principal Investigator |
| Jennifer Rose-Nussbaumer, MD | Stanford University | Principal Investigator |
| Nicole Varnado, MPH | Stanford University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Federal University of São Paulo | São Paulo | Brazil | ||||
| Aravind Eye Care System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42348235 | Derived | Prajna NV, Bernard A, Prajna L, Rajaraman R, Sharma SS, Christy J, Radhakrishnan N, Mandlik K, De Freitas D, Hofling-Lima AL, Varnado NE, Abdelrahman S, Arnold BF, Lietman TM, Rose-Nussbaumer J; REAGIR Research Group. Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction: Follow-Up of a Randomized Clinical Trial. JAMA Ophthalmol. 2026 Jun 25. doi: 10.1001/jamaophthalmol.2026.2257. Online ahead of print. | |
| 41561665 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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. |
| FG001 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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 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 within 24 hours after the procedure. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Best Spectacle-Corrected Visual Acuity | Best Spectacle-Corrected Visual Acuity | Posted | Mean | Standard Deviation | logMAR | 6 Months |
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-elective surgery, hospitalization, or loss of function | Injury, poisoning and procedural complications | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increase in hypopyon (increase >2mm) | Eye disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sarah Abdelrahman | F.I. Proctor Foundation | 7143064525 | Sarah.abdelrahman@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 3, 2024 | Sep 15, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 3, 2024 | Sep 15, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015823 | Acanthamoeba Keratitis |
| ID | Term |
|---|---|
| D015822 | Eye Infections, Parasitic |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000562 | Amebiasis |
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| ID | Term |
|---|---|
| C010882 | chlorhexidine gluconate |
| D010866 | Natamycin |
| D012395 | Rose Bengal |
| D000094504 | Corneal Cross-Linking |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D005452 | Fluoresceins |
Not provided
Not provided
| OTHER |
Not provided
Not provided
Not provided
Not provided
| Chlorhexidine Gluconate | Drug | Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis. |
|
| Natamycin | Drug | Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. |
|
| Rose Bengal | Drug | 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 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 within 24 hours after the procedure. |
|
|
| Placebo | Other | 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. |
|
| 3 Weeks, 3 Months, 6 Months 12 Months |
| Madurai |
| Tamil Nadu |
| India |
| Christy SJ, Mandlik K, Kumar V, Kanchugantla SSSM, Abdelrahman S, Rose-Nussbaumer J. Adjunctive tacrolimus in the treatment of fungal keratitis requiring therapeutic penetrating keratoplasty. Am J Ophthalmol Case Rep. 2025 Dec 29;41:102506. doi: 10.1016/j.ajoc.2025.102506. eCollection 2026 Mar. |
| 39192339 | Derived | Prajna NV, Lalitha P, Sharma S, de Freitas D, Hofling-Lima A, Varnado N, Abdelrahman S, Cavallino V, Arnold BF, Lietman TM, Rose-Nussbaumer J. A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study. Trials. 2024 Aug 28;25(1):566. doi: 10.1186/s13063-024-08376-3. |
| 39011096 | Derived | Prajna V, Prajna L, Sharma S, de Freitas D, Hofling-Lima AL, Varnado N, Abdelrahman S, Cavallino V, Arnold B, Lietman T, Rose-Nussbaumer J. A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthameoba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) Study. Res Sq [Preprint]. 2024 Jul 2:rs.3.rs-4165312. doi: 10.21203/rs.3.rs-4165312/v1. |
| BG001 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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 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 within 24 hours after the procedure. |
| BG002 | Total | Total of all reporting groups |
| Eyes |
|
| years |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants | No | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants | Participants |
|
| Visual Acuity (logMAR BSCVA) | Mean | Standard Deviation | logMar | Eyes |
|
| Central Corneal Thickness (μm) | Mean | Standard Deviation | μm | Eyes |
|
| Hypopyon | Count of Participants | Participants | Participants |
|
| Infiltrate/Scar Size (mm) | Mean | Standard Deviation | mm | Eyes |
|
| Fungal Culture (Positive) | Count of Participants | Participants | Participants |
|
| Fungal Smear (Positive) | Count of Participants | Participants | Participants |
|
| Acanthamoeba Culture | Count of Participants | Participants | Participants |
|
| Acanthamoeba Smear (Postive) | Count of Participants | Participants | Participants |
|
| Occupation | Count of Participants | Participants | Participants |
|
| Recent Eye Trauma | Count of Participants | Participants | Participants |
|
| Contact Menswear | Count of Participants | Participants | Participants |
|
| Uses Native Medicine | Count of Participants | Participants | Participants |
|
| Symptom Duration (Days) | Mean | Standard Deviation | days | Participants |
|
| OG001 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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 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 within 24 hours after the procedure. |
|
|
| Secondary | Best Spectacle-Corrected Visual Acuity | Best Spectacle-Corrected Visual Acuity | Loss to follow up | Posted | Mean | Standard Deviation | logMAR | 3 Weeks, 3 Months, 12 Months |
|
|
|
| Secondary | Scar Size | Geometric Mean | Loss to follow up or CP/TPK | Posted | Mean | Standard Deviation | mm | 3 Weeks, 3 Months, 6 Months 12 Months | Eyes | Eyes |
|
|
|
| 1 |
| 165 |
| 31 |
| 165 |
| 17 |
| 165 |
| EG001 | 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 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. 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. Natamycin: Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. 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 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 within 24 hours after the procedure. | 0 | 165 | 36 | 165 | 25 | 165 |
| Therapeutic Penetrating Keratoplasty | Eye disorders | Systematic Assessment |
|
| Corneal perforation | Eye disorders | Systematic Assessment |
|
| Therapeutic Penetrating Keratoplasty and Corneal Perforation | Eye disorders | Systematic Assessment |
|
| Increase in the longest diameter of infiltrate (>50% increase from baseline and >1mm) | Eye disorders | Systematic Assessment |
|
| Progressive corneal thinning, < 50% of enrollment thickness | Eye disorders | Systematic Assessment |
|
| Other | Eye disorders | Systematic Assessment |
|
Not provided
Not provided
| D011528 |
| Protozoan Infections |
| D007634 | Keratitis |
| D003316 | Corneal Diseases |
| D005128 | Eye Diseases |
| D015817 | Eye Infections |
| D013141 |
| Spiro Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D014966 | Xanthenes |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010778 | Photochemotherapy |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D010789 | Phototherapy |
| 3-month |
|
|
| 12- month |
|
|
|
| 3-months |
|
|
| 6-months |
|
|
| 12-months |
|
|