Fungal KeratitisPhase 3NCT00516399
A Clinical Trial of the Treatment of Fungal Corneal Ulcers With Povidone-Iodine
A Phase 3 study testing povidone-iodine 1.25% ophthalmic solution and natamycin ophthalmic suspension, USP 5% in people with Fungal Keratitis, run by University of California, Los Angeles.
Trial summary
The purpose of this study is to determine the effectiveness of 1.25% povidone-iodine ophthalmic solution for the treatment of small to medium sized fungal corneal ulcers compared with an antifungal antibiotic. Read more about this study
- Who is it for?
- Ages 1 month and older
- Conditions the study is for
- Fungal Keratitis
- What is being tested?
- povidone-iodine 1.25% ophthalmic solution and natamycin ophthalmic suspension, USP 5%
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- No sites listed yet
- Study dates
- Mar 2008to Dec 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 1 month and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Be more than 1 month old.
- Have a history of culture positive fungal corneal ulcer, that began within 14 days of presentation to the study center characterized by either a stromal defect with infiltrate or exudate, or a positive fungal stain on smear. Other clinical criteria to suspect fungal ulcers include firm (sometimes dry) elevated slough, "hyphate" lines extending beyond the ulcer edge into normal cornea, endothelial plaque, history of organic material striking the eye, intense inflammation of the cornea and anterior chamber, immune ring, Descemet's folds, multifocal granular (or feathery) grey-white satellite stromal infiltrates. A hypopyon may be present. The diameter of the ulcer will be between 1 mm and 6 mm, as long as there is no scleral involvement.
- It is acceptable to enroll a subject who has received a graft, provided the graft meets the following requirements:
- The central ulcer is well within the donor cornea.
- There is no suture abscess.
- The graft has not previously failed.
- The subject should not have a foreign body present on or in the cornea or eye. A subject can be enrolled after the foreign body is totally removed and the other enrollment criteria are met.
Who cannot join
- The initial culture fails to show the presence of fungi.
- The patient has a history of allergy to povidone-iodine, iodine, or natamycin.
- The cornea or sclera has been perforated or perforation is impending.
- The unaffected eye is legally blind.
- Dacrocystitis is present.
- Neurotrophic keratitis, exposure keratitis or keratitis sicca is present.
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- Prescribed topical or systemic steroids or other immunosuppressants are being used, unless discontinued before randomization.
- The patient is known to be HIV positive.
- The infiltrate extends into the posterior one-third of the stroma.
- The initial culture shows significant growth of bacteria (>10 colonies).
- Any topical antifungal agent has been used within the past week.
- Both eyes are infected.
About this study
The purpose of this study is to determine the effectiveness of 1.25% povidone-iodine ophthalmic solution for the treatment of small to medium sized fungal corneal ulcers compared with an antifungal antibiotic.
Read the detailed description
The medication to be studied is 1.25% povidone-iodine solution and the control medication is 5% natamycin ophthalmic suspension. The povidone-iodine concentration of 1.25% was chosen based on a study using povidone-iodine ophthalmic solution for the first week after ocular surgery. Initially, some patients complained of a stinging sensation when using the 2.5% concentration. This might prevent full compliance from some subjects. When the solution was diluted to 1.25%, there were no more complaints of discomfort. Therefore, in the actual one-week postoperative clinical trial, the 1.25 % concentration was used without any patient complaints and it was found to be effective. In a pilot study conducted in the Philippines, investigating treatment of small to medium-sized fungal corneal ulcers, 1.25% povidone-iodine was shown to be effective against fungal corneal ulcers including those caused by Fusarium solani and Mycelia sterila when treated for 7-20 days.
The povidone-iodine 1.25% solution will be prepared by removing 1.875 ml. of solution from a 15 ml. bottle of Balanced Salt Solution (BSS), (Alcon Laboratories, Inc., Fort Worth) and inserting 1.875 ml. of a 10% povidone-iodine solution (Betadine solution, Purdue Frederick, Norwalk). Preparations will be made weekly for each subject using sterile technique and are to be stored in a cool dark place. The control anti-fungal will be natamycin ophthalmic suspension, USP 5% (Natamet, M.J. Pharmaceuticals Ltd., Mumbai, India), which represents the current standard of care. The subjects will be discharged home on the same randomized medication that they were assigned while hospitalized.
Prospective candidates for the study, and/or their parent or guardian, will review the appropriate Human Subjects Consent Form, approved by the Human Subjects Protection Committee of the Harbor-UCLA Medical Center. After written consents, Informed and HIPPA, are obtained, each subject will be randomized to receive either povidone-iodine or the control drug. All subjects will be hospitalized for a minimum duration of 7 days for careful monitoring and appropriate treatment. To assure compliance, all these inpatient subjects will have their medications administered by medical personnel. Upon admission, the intake clinical examination will be recorded.
Each infected eye will be randomly assigned by the research nurse to be treated with povidone-iodine 1.25% or the control, anti-fungal medication natamycin. Randomization will be achieved by using random number generated randomization schedules. To guarantee similar distribution will occur, and not be left to chance, each study site randomization schedule will be stratified on ulcer sizes < 3mm. and > 3mm.
The only eye medications permitted beside povidone-iodine 1.25% ophthalmic solution and the control drug natamycin, will be atropine ophthalmic solution to reduce intraocular inflammation and prevent synechiae, and anti-glaucoma medication as needed. The atropine will be administered to the affected eye(s) twice a day and strength will vary according to the subject's age. Subjects less than 1 year of age will be given atropine 0.25%, ages 1-3 will be given 0.5%, and subjects greater than 3 years of age will be given 1%.
The dosing schedule of povidone-iodine 1.25% or control medication is as follows:
- For the first three days, one drop of the medication will be applied every hour.
- Day 4 and thereafter, hourly while awake, when asleep, every three hours. Sleep is not to exceed 9 hours. Treat all cases with intense drop therapy for a minimum of 5 days unless criteria for change in therapy are met.
- At 5 days, decrease dosing frequency to every 2 hours while awake until "cured", only if no deterioration in any factor and improved in at least one factor, other than epithelial defect, is noted on 2 consecutive examinations.
- If at 10 days the status remains unchanged, the subject is to exit the study.
- After discharge, dosing frequency is to remain every 2 hours while awake until cured.
- Conditions
- Fungal Keratitis
- Being tested
- povidone-iodine 1.25% ophthalmic solution, natamycin ophthalmic suspension, USP 5%
- Keywords
- Fungal keratitis, povidone iodine, childhood blindness, povidone-iodine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
povidone-iodine 1.25% ophthalmic solutionDrug
Also called Betadine, Purdue Frederick, Norwalk
natamycin ophthalmic suspension, USP 5%Drug
Also called Natamet, M.J. Pharmaceuticals Ltd., Mumbai, India
| Study group | Role | What they receive |
|---|---|---|
| I: | Experimental | povidone-iodine 1.25% ophthalmic solution. The associated intervention descriptions contain sufficient information to describe the arm. Receives: Drug: povidone-iodine 1.25% ophthalmic solution |
| II | Active comparator | natamycin ophthalmic suspension, USP 5%. The associated intervention descriptions contain sufficient information to describe the arm. Receives: Drug: natamycin ophthalmic suspension, USP 5% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of days until disappearance of hypopyon and criteria for recovery and cure are met and subject is discharged home. Number of treatment failures. Ocular complications from the infection and ocular and systemic complications from the treatment.
Measured: Inferior outcome is defined as cure time under povidone-iodine treatment, which is at least 4 days longer than cure time under natamycin, or time until criteria for improvement to hospital discharge is reached.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2007 (estimated)
- Study startMar 2008
- Primary completionSep 2010
- Study completionDec 2010
Why it stopped: The DSMC decided it appeared futile to attempt to demonstrate non-inferiority of povidone-iodine to Natamycin.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fungal KeratitisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Responsible party
- Principal investigator, Sherwin J. Isenberg, University of California, Los Angeles
- Investigators
- Sherwin J. Isenberg, M.D., Principal investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00516399
- Sponsor's protocol ID
- 012488-01-00
- Status last verified
- Dec 2014
- First submitted
- 14 Aug 2007
- Last updated
- 4 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial of the Treatment of Fungal Corneal Ulcers With Povidone-Iodine
- ClinicalTrials.gov ID
- NCT00516399
- Acronym / sponsor ID
- 012488-01-00
- Conditions
- Fungal Keratitis
- Keywords
- Fungal keratitis, povidone iodine, childhood blindness, povidone-iodine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The DSMC decided it appeared futile to attempt to demonstrate non-inferiority of povidone-iodine to Natamycin.
- Enrolment
- 78 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Study start
- Mar 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 15 Aug 2007 (estimated)
- Results
- Not posted in the source record
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 study is to determine the effectiveness of 1.25% povidone-iodine ophthalmic solution for the treatment of small to medium sized fungal corneal ulcers compared with an antifungal antibiotic.
Detailed description
The medication to be studied is 1.25% povidone-iodine solution and the control medication is 5% natamycin ophthalmic suspension. The povidone-iodine concentration of 1.25% was chosen based on a study using povidone-iodine ophthalmic solution for the first week after ocular surgery. Initially, some patients complained of a stinging sensation when using the 2.5% concentration. This might prevent full compliance from some subjects. When the solution was diluted to 1.25%, there were no more complaints of discomfort. Therefore, in the actual one-week postoperative clinical trial, the 1.25 % concentration was used without any patient complaints and it was found to be effective. In a pilot study conducted in the Philippines, investigating treatment of small to medium-sized fungal corneal ulcers, 1.25% povidone-iodine was shown to be effective against fungal corneal ulcers including those caused by Fusarium solani and Mycelia sterila when treated for 7-20 days.
The povidone-iodine 1.25% solution will be prepared by removing 1.875 ml. of solution from a 15 ml. bottle of Balanced Salt Solution (BSS), (Alcon Laboratories, Inc., Fort Worth) and inserting 1.875 ml. of a 10% povidone-iodine solution (Betadine solution, Purdue Frederick, Norwalk). Preparations will be made weekly for each subject using sterile technique and are to be stored in a cool dark place. The control anti-fungal will be natamycin ophthalmic suspension, USP 5% (Natamet, M.J. Pharmaceuticals Ltd., Mumbai, India), which represents the current standard of care. The subjects will be discharged home on the same randomized medication that they were assigned while hospitalized.
Prospective candidates for the study, and/or their parent or guardian, will review the appropriate Human Subjects Consent Form, approved by the Human Subjects Protection Committee of the Harbor-UCLA Medical Center. After written consents, Informed and HIPPA, are obtained, each subject will be randomized to receive either povidone-iodine or the control drug. All subjects will be hospitalized for a minimum duration of 7 days for careful monitoring and appropriate treatment. To assure compliance, all these inpatient subjects will have their medications administered by medical personnel. Upon admission, the intake clinical examination will be recorded.
Each infected eye will be randomly assigned by the research nurse to be treated with povidone-iodine 1.25% or the control, anti-fungal medication natamycin. Randomization will be achieved by using random number generated randomization schedules. To guarantee similar distribution will occur, and not be left to chance, each study site randomization schedule will be stratified on ulcer sizes < 3mm. and > 3mm.
The only eye medications permitted beside povidone-iodine 1.25% ophthalmic solution and the control drug natamycin, will be atropine ophthalmic solution to reduce intraocular inflammation and prevent synechiae, and anti-glaucoma medication as needed. The atropine will be administered to the affected eye(s) twice a day and strength will vary according to the subject's age. Subjects less than 1 year of age will be given atropine 0.25%, ages 1-3 will be given 0.5%, and subjects greater than 3 years of age will be given 1%.
The dosing schedule of povidone-iodine 1.25% or control medication is as follows:
- For the first three days, one drop of the medication will be applied every hour.
- Day 4 and thereafter, hourly while awake, when asleep, every three hours. Sleep is not to exceed 9 hours. Treat all cases with intense drop therapy for a minimum of 5 days unless criteria for change in therapy are met.
- At 5 days, decrease dosing frequency to every 2 hours while awake until "cured", only if no deterioration in any factor and improved in at least one factor, other than epithelial defect, is noted on 2 consecutive examinations.
- If at 10 days the status remains unchanged, the subject is to exit the study.
- After discharge, dosing frequency is to remain every 2 hours while awake until cured.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| I: | Experimental | Drug: povidone-iodine 1.25% ophthalmic solutionpovidone-iodine 1.25% ophthalmic solution. The associated intervention descriptions contain sufficient information to describe the arm. |
| II | Active comparator | Drug: natamycin ophthalmic suspension, USP 5%natamycin ophthalmic suspension, USP 5%. The associated intervention descriptions contain sufficient information to describe the arm. |
Who may qualify
- Ages
- 1 month and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Be more than 1 month old.
- Have a history of culture positive fungal corneal ulcer, that began within 14 days of presentation to the study center characterized by either a stromal defect with infiltrate or exudate, or a positive fungal stain on smear. Other clinical criteria to suspect fungal ulcers include firm (sometimes dry) elevated slough, "hyphate" lines extending beyond the ulcer edge into normal cornea, endothelial plaque, history of organic material striking the eye, intense inflammation of the cornea and anterior chamber, immune ring, Descemet's folds, multifocal granular (or feathery) grey-white satellite stromal infiltrates. A hypopyon may be present. The diameter of the ulcer will be between 1 mm and 6 mm, as long as there is no scleral involvement.
- It is acceptable to enroll a subject who has received a graft, provided the graft meets the following requirements:
- The subject should not have a foreign body present on or in the cornea or eye. A subject can be enrolled after the foreign body is totally removed and the other enrollment criteria are met.
Key exclusion criteria (12 listed)
- The initial culture fails to show the presence of fungi.
- The patient has a history of allergy to povidone-iodine, iodine, or natamycin.
- The cornea or sclera has been perforated or perforation is impending.
- The unaffected eye is legally blind.
- Dacrocystitis is present.
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 |
|---|---|---|
| povidone-iodine 1.25% ophthalmic solutionAlso: Betadine, Purdue Frederick, Norwalk | Drug | I: |
| natamycin ophthalmic suspension, USP 5%Also: Natamet, M.J. Pharmaceuticals Ltd., Mumbai, India | Drug | II |
Primary outcome
Number of days until disappearance of hypopyon and criteria for recovery and cure are met and subject is discharged home. Number of treatment failures. Ocular complications from the infection and ocular and systemic complications from the treatment.
Time frame: Inferior outcome is defined as cure time under povidone-iodine treatment, which is at least 4 days longer than cure time under natamycin, or time until criteria for improvement to hospital discharge is reached.
Results and safety
The study was stopped early (reason given: The DSMC decided it appeared futile to attempt to demonstrate non-inferiority of povidone-iodine to Natamycin.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2014.
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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.
Sherwin J. Isenberg, M.D. principal investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing povidone-iodine 1.25% ophthalmic solution and natamycin ophthalmic suspension, USP 5% in people with Fungal Keratitis, run by University of California, Los Angeles.
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 7 inclusion and 12 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 4 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
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 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?
The study was stopped early (reason given: The DSMC decided it appeared futile to attempt to demonstrate non-inferiority of povidone-iodine to Natamycin.). Results are not available in the source record.
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 days until disappearance of hypopyon and criteria for recovery and cure are met and subject is discharged home. Number of treatment failures. Ocular complications from the infection and ocular and systemic complications from the treatment. (time frame: Inferior outcome is defined as cure time under povidone-iodine treatment, which is at least 4 days longer than cure time under natamycin, or time until criteria for improvement to hospital discharge is reached.). 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 4 Dec 2014.