Acanthamoeba KeratitisPhase 3REAGIRNCT05110001
Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction
A Phase 3 study testing Moxifloxacin Ophthalmic, Chlorhexidine Gluconate and Natamycin in people with Acanthamoeba Keratitis and Fungal Keratitis, run by University of California, San Francisco at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acanthamoeba Keratitis, Fungal Keratitis
- What is being tested?
- Moxifloxacin Ophthalmic, Chlorhexidine Gluconate and Natamycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 330 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 3 Aug 2022to 30 Jun 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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
Who cannot join
- 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
Show all 9Show fewer
- Pinhole visual acuity worse than 20/200 in the unaffected eye
- Participants who are decisionally and/or cognitively impaired
- Presence of demestocele at recruitment
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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:
Read more
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.
- Conditions
- Acanthamoeba Keratitis, Fungal Keratitis
- Being tested
- Moxifloxacin Ophthalmic, Chlorhexidine Gluconate, Natamycin, Rose Bengal, Placebo
- Medical subject headings
- Acanthamoeba Keratitis
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 a standard therapy for bacterial keratitis.
Chlorhexidine GluconateDrug
Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis.
NatamycinDrug
Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis.
Rose BengalDrug
Also called Corneal Cross Linking with 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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Moxifloxacin Ophthalmic; Drug: Chlorhexidine Gluconate; Drug: Natamycin; Other: Placebo |
| 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 Receives: Drug: Moxifloxacin Ophthalmic; Drug: Chlorhexidine Gluconate; Drug: Natamycin; Drug: Rose Bengal |
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 (2)
Best Spectacle-Corrected Visual Acuity
Best Spectacle-Corrected Visual Acuity
Measured: 3 Weeks, 3 Months, 12 Months
Scar Size
Geometric Mean
Measured: 3 Weeks, 3 Months, 6 Months 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2021
- Study start3 Aug 2022
- Primary completion14 Dec 2024
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acanthamoeba KeratitisStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- 330 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Aravind Eye Care System, National Eye Institute (NEI), Stanford University, Federal University of São Paulo
- Responsible party
- Sponsor
- Investigators
- Tom Lietman, MD, Principal investigator, University of California, San FrnascoJennifer Rose-Nussbaumer, MD, Principal investigator, Stanford UniversityNicole Varnado, MPH, Study director, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05110001
- Sponsor's protocol ID
- 18-26045-R
- Other IDs
- UG1EY028518
- Acronym
- REAGIR
- Status last verified
- Aug 2026
- First submitted
- 26 Oct 2021
- Last updated
- 3 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 Aug 1;144(8):775-779. doi: 10.1001/jamaophthalmol.2026.2257.
PubMed 42348235Christy 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.
PubMed 41561665Prajna 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.
PubMed 39192339Prajna 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.
PubMed 39011096
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction
- ClinicalTrials.gov ID
- NCT05110001
- Acronym / sponsor ID
- REAGIR / 18-26045-R
- Conditions
- Acanthamoeba Keratitis, Fungal Keratitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Aravind Eye Care System, National Eye Institute (NEI), Stanford University, Federal University of São Paulo
- Study start
- 3 Aug 2022 (actual)
- Primary completion
- 14 Dec 2024 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 5 Nov 2021 (actual)
- Results
- Posted 30 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Therapy | Placebo comparator | Drug: Moxifloxacin Ophthalmic, Drug: Chlorhexidine Gluconate, Drug: Natamycin, Other: PlaceboPatients 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 | Drug: Moxifloxacin Ophthalmic, Drug: Chlorhexidine Gluconate, Drug: Natamycin, Drug: Rose BengalPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
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 a standard therapy for bacterial keratitis. | Drug | Cross-Linking with rose Bengal (RB-PDT), Standard Therapy |
| Chlorhexidine GluconateTopical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis. | Drug | Cross-Linking with rose Bengal (RB-PDT), Standard Therapy |
| NatamycinNatamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis. | Drug | Cross-Linking with rose Bengal (RB-PDT), Standard Therapy |
| Rose BengalAlso: Corneal Cross Linking with rose BengalStudy 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. | Drug | Cross-Linking with rose Bengal (RB-PDT) |
| PlaceboStudy 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. | Other | Standard Therapy |
Primary outcome
Best Spectacle-Corrected Visual Acuity
Time frame: 6 Months
Best Spectacle-Corrected Visual Acuity
2 secondary outcomes
Best Spectacle-Corrected Visual Acuity
Time frame: 3 Weeks, 3 Months, 12 Months
Scar Size
Time frame: 3 Weeks, 3 Months, 6 Months 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42348235Prajna 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 Aug 1;144(8):775-779. doi: 10.1001/jamaophthalmol.2026.2257.
- Derived from this study: PubMed 41561665Christy 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.
- Derived from this study: PubMed 39192339Prajna 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.
- Derived from this study: PubMed 39011096Prajna 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.
- 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 Frnasco
Jennifer Rose-Nussbaumer, MD principal investigator
Stanford University
Nicole Varnado, MPH study director
Stanford University
2 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, Chlorhexidine Gluconate and Natamycin in people with Acanthamoeba Keratitis and Fungal Keratitis, run by University of California, San Francisco at 2 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 9 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 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil, 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?
Yes. Results are posted in the registry (first posted 30 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 NCT05110001, which also lists 4 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 Sep 2026.