A Comparison of Three Fluoroquinolone Topical Eyedrops in the Treatment of Infectious Corneal Ulcers.

This is a prospective, single masked, comparative, mono-therapeutic trial evaluating three fluoroquinolone agents that are approved and marketed for the treatment of conjunctivitis. Approximately 120 patients who have corneal ulcers greater than 2 mm but less than 6 mm in size who meet all other inclusion criteria will be enrolled into this study. Patients will be randomized in a 2:1:1 ratio to receive besifloxacin 0.6% ophthalmic suspension, gatifloxacin 0.5% ophthalmic solution, or moxifloxacin 0.5% ophthalmic solution.

• Besivance 0.6% Ophthalmic Suspension (Drug), also known as Besifloxacin 0.6% Ophthalmic Suspension: Drop to be applied in affected eye initially every hour for the first 48 hours then doses will be reduced at each subsequent visit by 50% if patient continues to show a reduction in size of 25% from the previous visit up to every 4 hours. If subject dose has been reduced to every 4 hours at visit 3 and shows an additional reduction size of 25% at visit 4, then they will be reduced to every 6 hours.
• Zymaxid 0.5% Ophthalmic Solution (Drug), also known as Gatifloxacin 0.5% Ophthalmic Solution: Drop to be applied in affected eye initially every hour for the first 48 hours then doses will be reduced at each subsequent visit by 50% if patient continues to show a reduction in size of 25% from the previous visit up to every 4 hours. If subject dose has been reduced to every 4 hours at visit 3 and shows an additional reduction size of 25% at visit 4, then they will be reduced to every 6 hours.
• Vigamox 0.5% Ophthalmic Solution (Drug), also known as Moxifloxacin Hydrochloride 0.5% Ophthalmic Solution: Drop to be applied in affected eye initially every hour for the first 48 hours then doses will be reduced at each subsequent visit by 50% if patient continues to show a reduction in size of 25% from the previous visit up to every 4 hours. If subject dose has been reduced to every 4 hours at visit 3 and shows an additional reduction size of 25% at visit 4, then they will be reduced to every 6 hours.

Primary outcomes

• Complete Healing [29 days]: The primary outcome will be complete healing of the corneal ulcer, defined as complete reepithelialization by Day 29.

Secondary outcomes

• Healing Rate [29 days]: Time to corneal ulcer reduction and/or total healing over a treatment course of 21 days.

Other outcomes

• Time to Treatment Failure. [8 days]: If there is no reduction in size of the corneal ulcer by day 8, the treatment will be deemed a failure and alternative medications will be given at the discretion of the investigator.
• Scarring [29 days]: Scarring will be evaluated and measured in millimeters at Day 29 and classified as either peripheral or central.
• Patient Satisfaction Scores [Average of 6 times in a 29 day period]: Patient satisfaction outcomes will be assessed using a series of survey questions ranging in both categorical and continuous outcomes. Treatment will be compared using either methods for differences in binomial proportions or the Wilcoxon Rank Sum test. Scale= 0- Very Comfortable, 1- Comfortable, 2- Uncomfortable, 3- Very Uncomfortable
• Patient Pain Scores [Average of 6 times in a 29 day period]: Patients will be asked to grade the overall pain of the affected eye at each visit on a Scale= 0--None, 1- Mild, 2- Moderate, 3- Severe
• Number of Participants With Treatment Failure [29 days]

Sex: All, ages: 18 Years to 90 Years

Inclusion Criteria:

1. Patients must be between the ages of 18-90 years of age.
2. Patients must be able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.
3. Patients must have a corneal ulcer greater than 2mm but less than 6mm in size.
4. Patients must have corneal ulcer present in only one eye.
5. Patients must agree not to wear contact lenses while on study.

Exclusion Criteria:

1. Patients with multifocal ulcers.
2. Signs of any other viral or fungal infection.
3. Treatment with antibiotics within 14 days of study entry.
4. Treatment with systemic or topical ocular antiviral agents or systemic or topical steroids or topical ocular nonsteroidal anti-inflammatory drugs (NSAIDS) during the prior 14-day period.
5. Known hypersensitivity or allergy to steroids (Loteprednol etabonate) or to any of the ingredients in the three study drugs (Besifloxacin 0.6% or Gatifloxacin 0.5% or Moxifloxacin 0.5%).
6. Contact lens only with no spectacles available.
7. Ocular surgery (including laser surgery) in either eye within 6 weeks prior to entry into this study.
8. Participation in any investigational study within the past 30 days.
9. Pregnant women, minors, or those not able to consent for themselves.

Participant flow

Outcome results

• Complete Healing (Primary), Number, participant: Besivance 0.6% Ophthalmic Suspension ; Zymaxid 0.5% Ophthalmic Solution 1; Vigamox 0.5% Ophthalmic Solution 1
• Healing Rate (Secondary), Number, Days: Besivance 0.6% Ophthalmic Suspension ; Zymaxid 0.5% Ophthalmic Solution 21; Vigamox 0.5% Ophthalmic Solution 21
• Time to Treatment Failure. (Other pre specified)
• Scarring (Other pre specified), Number, millimeters: Besivance 0.6% Ophthalmic Suspension ; Zymaxid 0.5% Ophthalmic Solution 0; Vigamox 0.5% Ophthalmic Solution 0
• Patient Satisfaction Scores (Other pre specified), Number, units on a scale: Besivance 0.6% Ophthalmic Suspension ; Zymaxid 0.5% Ophthalmic Solution 0; Vigamox 0.5% Ophthalmic Solution 2
• Patient Pain Scores (Other pre specified), Number, units on a scale: Besivance 0.6% Ophthalmic Suspension ; Zymaxid 0.5% Ophthalmic Solution 0; Vigamox 0.5% Ophthalmic Solution 2
• Number of Participants With Treatment Failure (Other pre specified), Number, participants: Besivance 0.6% Ophthalmic Suspension ; Zymaxid 0.5% Ophthalmic Solution 0; Vigamox 0.5% Ophthalmic Solution 0

Adverse events

Time frame: 29 days

Limitations and caveats: The study was terminated due to slow enrollment.

• Ira A. Shivitz, M.D., Principal investigator, Cornea Consultants Of Nashville