A Clinical Trial of the Treatment of Fungal Corneal Ulcers With Povidone-Iodine

This study has been terminated.
(The DSMC decided that it appeared futile to attempt to demonstrate non-inferiority of povidone-iodine to Natamycin.)
Sponsor:
Collaborator:
Los Angeles Biomedical Research Institute
Information provided by (Responsible Party):
Sherwin J. Isenberg, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00516399
First received: August 14, 2007
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Fungal Keratitis
Infected Corneal Ulcers
Drug: povidone-iodine 1.25% ophthalmic solution
Drug: natamycin ophthalmic suspension, USP 5%
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Clinical Trial of the Treatment of Fungal Corneal Ulcers With Povidone-Iodine

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]

Enrollment: 78
Study Start Date: March 2008
Study Completion Date: December 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I:
povidone-iodine 1.25% ophthalmic solution. The associated intervention descriptions contain sufficient information to describe the arm.
Drug: povidone-iodine 1.25% ophthalmic solution
Other Name: Betadine, Purdue Frederick, Norwalk
Active Comparator: II
natamycin ophthalmic suspension, USP 5%. The associated intervention descriptions contain sufficient information to describe the arm.
Drug: natamycin ophthalmic suspension, USP 5%
Other Name: Natamet, M.J. Pharmaceuticals Ltd., Mumbai, India

  Hide Detailed Description

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:

  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.
  Eligibility

Ages Eligible for Study:   1 Month and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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.

Exclusion Criteria:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516399

Sponsors and Collaborators
University of California, Los Angeles
Los Angeles Biomedical Research Institute
Investigators
Principal Investigator: Sherwin J. Isenberg, M.D. Los Angeles Biomedical Research Institute
  More Information

No publications provided

Responsible Party: Sherwin J. Isenberg, Chief, Division of Ophthalmology, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00516399     History of Changes
Other Study ID Numbers: 012488-01-00
Study First Received: August 14, 2007
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
Fungal keratitis
infected corneal ulcers
povidone iodine
childhood blindness
povidone-iodine

Additional relevant MeSH terms:
Corneal Ulcer
Keratitis
Ulcer
Eye Infections
Infection
Corneal Diseases
Eye Diseases
Pathologic Processes
Povidone
Ophthalmic Solutions
Iodine
Cadexomer iodine
Natamycin
Povidone-Iodine
Pharmaceutical Solutions
Plasma Substitutes
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anti-Bacterial Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 26, 2014