A Clinical Trial of the Treatment of Fungal Corneal Ulcers With Povidone-Iodine
Information source: University of California, Los Angeles
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fungal Keratitis; Infected Corneal Ulcers
Intervention: povidone-iodine 1.25% ophthalmic solution (Drug); natamycin ophthalmic suspension, USP 5% (Drug)
Phase: Phase 3
Sponsored by: University of California, Los Angeles
Official(s) and/or principal investigator(s):
Sherwin J. Isenberg, M.D., Principal Investigator, Affiliation: Los Angeles Biomedical Research Institute
Sherwin J. Isenberg, M.D., Phone: (310) 222-2731, Email: firstname.lastname@example.org
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.
Official title: A Clinical Trial of the Treatment of Fungal Corneal Ulcers With Povidone-Iodine
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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.
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:
1. For the first three days, one drop of the medication will be applied every hour.
2. 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.
3. 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.
4. If at 10 days the status remains unchanged, the subject is to exit the study.
5. After discharge, dosing frequency is to remain every 2 hours while awake until cured.
Minimum age: 1 Month.
Maximum age: N/A.
1. Be more than 1 month old.
2. 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.
3. It is acceptable to enroll a subject who has received a graft, provided the graft
meets the following requirements:
1. The central ulcer is well within the donor cornea.
2. There is no suture abscess.
3. The graft has not previously failed.
4. 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.
1. The initial culture fails to show the presence of fungi.
2. The patient has a history of allergy to povidone-iodine, iodine, or natamycin.
3. The cornea or sclera has been perforated or perforation is impending.
4. The unaffected eye is legally blind.
5. Dacrocystitis is present.
6. Neurotrophic keratitis, exposure keratitis or keratitis sicca is present.
7. Prescribed topical or systemic steroids or other immunosuppressants are being used,
unless discontinued before randomization.
8. The patient is known to be HIV positive.
9. The infiltrate extends into the posterior one-third of the stroma.
10. The initial culture shows significant growth of bacteria (>10 colonies).
11. Any topical antifungal agent has been used within the past week.
12. Both eyes are infected.
Locations and Contacts
Sherwin J. Isenberg, M.D., Phone: (310) 222-2731, Email: email@example.com
Los Angeles Biomedical Research Institute, Torrance, California 90502, United States; Recruiting
Sherwin J Isenberg, M.D., Phone: 310-222-2731, Email: firstname.lastname@example.org
Sherwin J. Isenberg, M.D., Principal Investigator
Starting date: March 2008
Last updated: May 27, 2011