Parasitic Ulcer Treatment Trial Pilot

Study Overview
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Brief Summary
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This is a study of optimal treatments for acanthamoeba keratitis. In the first part of the study, participants will be randomized to chlorhexidine monotherapy or chlorhexidine plus povidone iodine. After four weeks of therapy, participants will be re-randomized to early corticosteroids, later corticosteroids, or placebo.

Detailed Description
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Acanthamoeba keratitis is a rare eye infection that is difficult to treat. The mainstay of therapy is a biguanide agent such as chlorhexidine, though recent studies have found povidone iodine to be effective for killing acanthamoeba organisms in vitro. Thus, we randomize participants to topical chlorhexidine 0.04% monotherapy (i.e., routine care) versus topical chlorhexidine 0.04% plus topical poviodine iodine 2.5%. The primary outcome is clearance of acanthamoeba from the ocular surface at 4 weeks. The role of topical corticosteroids in acanthamoeba keratitis is controversial. Topical corticosteroids can promote growth of acanthamoeba, but may also reduce inflammation and vision-threatening complications of infection. Here, we randomize participants who have completed a course of anti-amoebic therapy to one of three groups: early prednisolone sodium phosphate 1% (started at 4 weeks), late prednisolone sodium phosphate 1% (started at 6 weeks) or placebo (started at 4 weeks). The primary outcome will be visual acuity at 6 months.

Official Title
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Parasitic Ulcer Treatment Trial Pilot

Conditions
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Acanthamoeba Keratitis

Intervention / Treatment
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* Drug: Chlorhexidine
* Drug: Povidone-Iodine
* Drug: Prednisolone Sodium Phosphate
* Drug: Hydroxypropyl Methylcellulose
* Drug: Prednisolone Sodium Phosphate
* Drug: Hydroxypropyl Methylcellulose


Participation Criteria
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Eligibility Criteria
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Trial 1 Inclusion Criteria: Smear or culture positive for acanthamoeba Age 13 years or greater Trial 1 Exclusion Criteria: Interstitial or viral keratitis on history or examination Corneal perforation Therapeutic keratoplasty for acanthamoeba keratitis Unwillingness or inability to follow-up (e.g., living too far from hospital) Trial 2 Inclusion Criteria Smear or culture positive for acanthamoeba, with 4 weeks of anti-amoebic treatment Age 13 years or greater Willing to participate in study Trial 2 Exclusion Criteria Interstitial or viral keratitis on history or examination Fungus identified on culture and smear after 2 weeks of anti-amoebic treatment Corneal perforation Therapeutic keratoplasty for acanthamoeba keratitis Unwillingness or inability to follow-up (e.g., living too far from hospital)

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chlorhexidine monotherapy<br>Topical chlorhexidine 0.04% | Drug: Chlorhexidine<br>* 1 drop half-hourly for days 1-2, then hourly for days 3-6, then 8 times daily until the 4-week visit<br>|
| Experimental: Chlorhexidine plus povidone iodine<br>Topical chlorhexidine 0.04% plus povidone iodine 2.5% | Drug: Chlorhexidine<br>* 1 drop half-hourly for days 1-2, then hourly for days 3-6, then 8 times daily until the 4-week visit<br>Drug: Povidone-Iodine<br>* 1 drop half-hourly for days 1-2, then hourly for days 3-6, then 8 times daily until the 4-week visit<br>|
| Experimental: Early corticosteroids<br>Topical prednisolone sodium phosophate 1% for weeks 4-11 | Drug: Prednisolone Sodium Phosphate<br>* 1 drop 4 times daily for weeks 4-9, then 2 times daily for weeks 10-11<br>|
| Experimental: Late corticosteroids<br>Artificial tears for weeks 4-5, then topical prednisolone sodium phosophate 1% for weeks 6-11 | Drug: Prednisolone Sodium Phosphate<br>* 1 drop 4 times daily for weeks 6-9, then 2 times daily for weeks 10-11<br>Drug: Hydroxypropyl Methylcellulose<br>* 1 drop 4 times daily for weeks 4-5<br>|
| Placebo Comparator: Placebo<br>Artificial tears for weeks 4-11 | Drug: Hydroxypropyl Methylcellulose<br>* 1 drop 4 times daily for weeks 4-9, then 2 times daily for weeks 10-11<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial 1: Microbial clearance | Acanthamoeba culture | 4 weeks | 
| Trial 2: Best spectacle corrected visual acuity |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial 1: Best spectacle corrected visual acuity |  | 4 weeks | 
| Trial 1: Time to re-epithelialization |  | 4 weeks | 
| Trial 1: Clinical cure |  | 4 weeks | 
| Trial 2: Time to clinical cure |  | 6 months |