Eye Infections, BacterialPhase 4NCT04981860
Comparison of Conjunctival Antimicrobial Activity and Patient Comfort Between Topical Hypochlorous Acid (Avenova) and Betadine
A Phase 4 study testing Betadine and AvenovaTM in people with Eye Infections, Bacterial, run by University of Miami at 2 sites in United States.
Trial summary
The purpose of this research study is to find out how Avenova (0.01 % hypochlorous acid) works compared to Betadine (Povidone iodide) for reducing bacteria and patient discomfort in the eyes. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Eye Infections, Bacterial
- What is being tested?
- Betadine and AvenovaTM
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Aug 2021to 27 Jun 2022
- Phase
- Phase 4
- 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
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Treatment Naïve patients:
- Any patient who is able to give consent for the study and did not receive an intravitreal injection in the past 6 months
- Patients receiving injections:
- Patient currently undergoing treatment for which he/she receives a intravitreal injection in one eye.
Who cannot join
- Treatment Naïve patients:
- Intravitreal injections in the past 6 months
- Use of eye drops for treatment of glaucoma in the past 6 months
- Use of eye drops with antibiotics or steroids in the past 6 months
- Patients receiving injections:
- Patient receiving injections in both eyes
Show all 14Show fewer
- Use of eye drops for treatment of glaucoma in the past 6 months
- Use of eye drops with antibiotics or steroids in the past 6 months
- Have any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.
- For both groups:
- Adults unable to consent
- Individuals who are not yet adults (infants, children, teenagers)
- Pregnant women
- Prisoners
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Bascom Palmer Eye Institute
Palm Beach Gardens, Florida, 33418
Medical Center Ophthalmology Associates
San Antonio, Texas, 78240
About this study
The purpose of this research study is to find out how Avenova (0.01 % hypochlorous acid) works compared to Betadine (Povidone iodide) for reducing bacteria and patient discomfort in the eyes.
Read the detailed description
About two percent of the population have an iodine allergy 1. A percentage of this population will also have a reaction to iodine-containing agents, including povidone iodine (PI) (Betadine®), which is the current standard of care for anti-septic preparation for conjunctival procedures. Despite being known to have a toxic effect on the cornea 2 and causing allergic reactions in some individuals, povidone Iodine (PI) (Betadine®) is still the most commonly used antiseptic agent for surgical scrub. Currently, there are no equivalent alternative prep agents available, although chlorhexidine has occasionally served as an alternative to povidone iodine (PI) (Betadine®) with variable results 2. Some studies have reported significantly less pain in patients prepped with chlorhexidine compared to povidone iodine (PI) (Betadine®) 2, and other studies have demonstrated that chlorhexidine has equal efficacy to povidone iodine (PI)(Betadine®) in decreasing the colony forming units of microbes both in vitro and in vivo 3. Although there have been no known reported allergies to chlorhexidine, it is known to be toxic to the cornea (leading to severe keratitis) and has proven to be less effective against methicillin-resistant Staphylococcus aureus(MRSA) 4.
The use of 0.01% hypochlorous acid (HOCl) in saline solution as an antiseptic agent has been gaining popularity as a possible alternative to povidone iodine (PI) (Betadine®). Hypochlorous acid (HOCl) is produced in vivo by neutrophils and causes oxidation of microbial nucleotides and inactivation of microbial enzymes, leading to cell death. Hypochlorous acid (HOCl) has a faster optimal kill-time for flora common to the eye 4, and has proven to be non-cytotoxic and well tolerated for continuous use 4,5,6. In vitro studies of 0.01% hypochlorous acid (HOCl) were found to have equal or more efficacious antiseptic properties compared with povidone iodine (PI) (Betadine®) and other potential antiseptic agents including chlorohexidine and isopropyl alcohol 4.
Currently, two concentrations of HOCl are available for commercial use: AvenovaTM with Neutrox™ (0.01% HOCl) and an over the counter product (0.02% HOCl). Both concentrations are used to treat blepharitis. Debabov et al5 presented toxicity data concluding that 0.01% hypochlorous acid (HOCl) (Avenova™ with Neutrox™) proved to be non-cytotoxic in comparison to the 0.02% hypochlorous acid (HOCl) product which was cytotoxic thus supporting the potential benefit of HOCl.
Stroman et al6 2017 concludes that hypochlorous acid (HOCl)in saline solution reduced bacterial colony load significantly without altering the variation of remaining bacterial species. Additionally, hypochlorous acid (HOCl) has been shown to reduce the population of bacterial and fungal species common to the lids and lashes by ≥ 99.9% 7. Despite the use of hypochlorous acid (HOCl) as a topical antiseptic on the eyelid, there have been no reports of its use as an antiseptic agent for conjunctival procedures. Many studies have confirmed that flora of the eyelid and eyelash only differ in their concentrations 8. Since hypochlorous acid (HOCl) has been found to be effective in reducing colony forming units and since the flora species of the conjunctiva, eyelid and eyelashes are equivalent, we propose that hypochlorous acid (HOCl) may serve as an alternative to povidone iodine (PI) (Betadine®) as a conjunctival procedure prep agent. Considering there were no reported negative side effects of hypochlorous acid (HOCl) contact with the eye, hypochlorous acid (HOCl) may prove to be a non-inferior alternative to povidone iodine (PI) (Betadine®). This may result in lower irritation and toxicity compared to povidone iodine (PI) (Betadine®)
- Conditions
- Eye Infections, Bacterial
- Being tested
- Betadine, AvenovaTM
- Medical subject headings
- Eye Infections, Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BetadineDrug
Also called Povidone Iodine
One drop of 5% povidone-iodine (Betadine) administered to the inferior conjunctiva of one eye. In the intravitreal injection groups, Betadine was given to the eye receiving the injection, as standard of care.
AvenovaTMDevice
Also called Hypochlorous Acid
One drop of 0.01% hypochlorous acid (Avenova) administered to the inferior conjunctiva of one eye. In the intravitreal injection groups, Avenova was given to the fellow (non-injected) eye. In the treatment-naive groups, the eye was assigned by randomization (Group L or Group R).
| Study group | Role | What they receive |
|---|---|---|
| Treatment naïve participants First Group L | Experimental | Treatment naïve participants randomized to receive Betadine on the left eye and Avenova on the right Eye Receives: Drug: Betadine; Device: AvenovaTM |
| Treatment naïve participants Second Group R | Experimental | Treatment naïve participants randomized to receive Avenova on the left eye and Betadine on the right Eye Receives: Drug: Betadine; Device: AvenovaTM |
| Participants undergoing intravitreal injection First Group L | Experimental | Participants undergoing intravitreal injection will receive betadine in the eye that is receiving injections and Avenova in the other eye. Group L are patients that are having intravitreal injections and will receive betadine in the left eye and Avenova in the right eye. Receives: Drug: Betadine; Device: AvenovaTM |
| Participants undergoing intravitreal injection Second Group R | Experimental | Participants undergoing intravitreal injection will receive betadine in the eye that is receiving injections and Avenova in the other eye. Group R are patients that are having intravitreal injections and will receive betadine in the right eye and Avenova in the left eye. Receives: Drug: Betadine; Device: AvenovaTM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Bacterial Colony Forming Units (CFU)
As assessed from sterile culture swab applied to the eye
Measured: Day 1
Secondary outcomes (1)
Post-Exposure Pain Score on Day 2 in the Avenova-Treated and Betadine-Treated Eyes
Pain in each eye was self-rated on the post-exposure questionnaire the morning after drug instillation (Day 2), on a numeric scale from 0 to 10, with higher scores indicating greater pain. The protocol described the scale as 1 to 10; scores of 0 were recorded and are reported as entered. No questionnaire was administered before instillation, so change from baseline could not be calculated; Day 2 scores are reported as absolute values. Scores are reported separately for the Avenova-treated eye and the Betadine-treated eye of each participant.
Measured: Day 2 (morning after instillation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2021
- Study start6 Aug 2021
- Primary completion27 Jun 2022
- Study completion27 Jun 2022
Why it stopped: The study was terminated early due to operational feasibility challenges, including multi-site coordination and administrative barriers. The study team determined continuation was not feasible, and all study activities were discontinued.
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.
- Other trials for Eye Infections, BacterialStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jorge Fortun, University of Miami
- Investigators
- Jorge Fortun, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04981860
- Sponsor's protocol ID
- 20200815
- Status last verified
- Jul 2025
- First submitted
- 27 Jul 2021
- Last updated
- 5 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Conjunctival Antimicrobial Activity and Patient Comfort Between Topical Hypochlorous Acid (Avenova) and Betadine
- ClinicalTrials.gov ID
- NCT04981860
- Acronym / sponsor ID
- 20200815
- Conditions
- Eye Infections, Bacterial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to operational feasibility challenges, including multi-site coordination and administrative barriers. The study team determined continuation was not feasible, and all study activities were discontinued.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- 6 Aug 2021 (actual)
- Primary completion
- 27 Jun 2022 (actual)
- Study completion
- 27 Jun 2022 (actual)
- First posted
- 29 Jul 2021 (actual)
- Results
- Posted 5 Nov 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to find out how Avenova (0.01 % hypochlorous acid) works compared to Betadine (Povidone iodide) for reducing bacteria and patient discomfort in the eyes.
Detailed description
About two percent of the population have an iodine allergy 1. A percentage of this population will also have a reaction to iodine-containing agents, including povidone iodine (PI) (Betadine®), which is the current standard of care for anti-septic preparation for conjunctival procedures. Despite being known to have a toxic effect on the cornea 2 and causing allergic reactions in some individuals, povidone Iodine (PI) (Betadine®) is still the most commonly used antiseptic agent for surgical scrub. Currently, there are no equivalent alternative prep agents available, although chlorhexidine has occasionally served as an alternative to povidone iodine (PI) (Betadine®) with variable results 2. Some studies have reported significantly less pain in patients prepped with chlorhexidine compared to povidone iodine (PI) (Betadine®) 2, and other studies have demonstrated that chlorhexidine has equal efficacy to povidone iodine (PI)(Betadine®) in decreasing the colony forming units of microbes both in vitro and in vivo 3. Although there have been no known reported allergies to chlorhexidine, it is known to be toxic to the cornea (leading to severe keratitis) and has proven to be less effective against methicillin-resistant Staphylococcus aureus(MRSA) 4.
The use of 0.01% hypochlorous acid (HOCl) in saline solution as an antiseptic agent has been gaining popularity as a possible alternative to povidone iodine (PI) (Betadine®). Hypochlorous acid (HOCl) is produced in vivo by neutrophils and causes oxidation of microbial nucleotides and inactivation of microbial enzymes, leading to cell death. Hypochlorous acid (HOCl) has a faster optimal kill-time for flora common to the eye 4, and has proven to be non-cytotoxic and well tolerated for continuous use 4,5,6. In vitro studies of 0.01% hypochlorous acid (HOCl) were found to have equal or more efficacious antiseptic properties compared with povidone iodine (PI) (Betadine®) and other potential antiseptic agents including chlorohexidine and isopropyl alcohol 4.
Currently, two concentrations of HOCl are available for commercial use: AvenovaTM with Neutrox™ (0.01% HOCl) and an over the counter product (0.02% HOCl). Both concentrations are used to treat blepharitis. Debabov et al5 presented toxicity data concluding that 0.01% hypochlorous acid (HOCl) (Avenova™ with Neutrox™) proved to be non-cytotoxic in comparison to the 0.02% hypochlorous acid (HOCl) product which was cytotoxic thus supporting the potential benefit of HOCl.
Stroman et al6 2017 concludes that hypochlorous acid (HOCl)in saline solution reduced bacterial colony load significantly without altering the variation of remaining bacterial species. Additionally, hypochlorous acid (HOCl) has been shown to reduce the population of bacterial and fungal species common to the lids and lashes by ≥ 99.9% 7. Despite the use of hypochlorous acid (HOCl) as a topical antiseptic on the eyelid, there have been no reports of its use as an antiseptic agent for conjunctival procedures. Many studies have confirmed that flora of the eyelid and eyelash only differ in their concentrations 8. Since hypochlorous acid (HOCl) has been found to be effective in reducing colony forming units and since the flora species of the conjunctiva, eyelid and eyelashes are equivalent, we propose that hypochlorous acid (HOCl) may serve as an alternative to povidone iodine (PI) (Betadine®) as a conjunctival procedure prep agent. Considering there were no reported negative side effects of hypochlorous acid (HOCl) contact with the eye, hypochlorous acid (HOCl) may prove to be a non-inferior alternative to povidone iodine (PI) (Betadine®). This may result in lower irritation and toxicity compared to povidone iodine (PI) (Betadine®)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment naïve participants First Group L | Experimental | Drug: Betadine, Device: AvenovaTMTreatment naïve participants randomized to receive Betadine on the left eye and Avenova on the right Eye |
| Treatment naïve participants Second Group R | Experimental | Drug: Betadine, Device: AvenovaTMTreatment naïve participants randomized to receive Avenova on the left eye and Betadine on the right Eye |
| Participants undergoing intravitreal injection First Group L | Experimental | Drug: Betadine, Device: AvenovaTMParticipants undergoing intravitreal injection will receive betadine in the eye that is receiving injections and Avenova in the other eye. Group L are patients that are having intravitreal injections and will receive betadine in the left eye and Avenova in the right eye. |
| Participants undergoing intravitreal injection Second Group R | Experimental | Drug: Betadine, Device: AvenovaTMParticipants undergoing intravitreal injection will receive betadine in the eye that is receiving injections and Avenova in the other eye. Group R are patients that are having intravitreal injections and will receive betadine in the right eye and Avenova in the left eye. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Any patient who is able to give consent for the study and did not receive an intravitreal injection in the past 6 months
- Patient currently undergoing treatment for which he/she receives a intravitreal injection in one eye.
Key exclusion criteria (14 listed)
- Intravitreal injections in the past 6 months
- Use of eye drops for treatment of glaucoma in the past 6 months
- Use of eye drops with antibiotics or steroids in the past 6 months
- Patient receiving injections in both eyes
- Use of eye drops for treatment of glaucoma in the past 6 months
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 |
|---|---|---|
| BetadineAlso: Povidone IodineOne drop of 5% povidone-iodine (Betadine) administered to the inferior conjunctiva of one eye. In the intravitreal injection groups, Betadine was given to the eye receiving the injection, as standard of care. | Drug | Participants undergoing intravitreal injection First Group L, Participants undergoing intravitreal injection Second Group R, Treatment naïve participants First Group L, Treatment naïve participants Second Group R |
| AvenovaTMAlso: Hypochlorous AcidOne drop of 0.01% hypochlorous acid (Avenova) administered to the inferior conjunctiva of one eye. In the intravitreal injection groups, Avenova was given to the fellow (non-injected) eye. In the treatment-naive groups, the eye was assigned by randomization (Group L or Group R). | Device | Participants undergoing intravitreal injection First Group L, Participants undergoing intravitreal injection Second Group R, Treatment naïve participants First Group L, Treatment naïve participants Second Group R |
Primary outcome
Number of Bacterial Colony Forming Units (CFU)
Time frame: Day 1
As assessed from sterile culture swab applied to the eye
1 secondary outcome
Post-Exposure Pain Score on Day 2 in the Avenova-Treated and Betadine-Treated Eyes
Time frame: Day 2 (morning after instillation)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Jorge Fortun, MD principal investigator
University of Miami
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Betadine and AvenovaTM in people with Eye Infections, Bacterial, run by University of Miami at 2 sites in United States.
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 4 inclusion and 14 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: stopped early, as of the sponsor's last update on 5 Nov 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 United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 5 Nov 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?
Number of Bacterial Colony Forming Units (CFU) (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2026.