Evaluating the Use of ProKera Plus® in the Management of Bacterial Corneal Ulcers

Study Overview
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Brief Summary
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The study design is a prospective, randomized, controlled interventional study to compare the outcome of ProKera Plus® with conventional treatment in patients with vision-threatening bacterial corneal ulcers. The study will be conducted at the University of Arkansas Medical Sciences (UAMS) in two phases for patients who present to an Ophthalmology clinic or Emergency Department at UAMS.

Detailed Description
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Bacterial keratitis is a serious bacterial infection of the cornea, usually caused by a persistent epithelial defect or ulcer that can lead to permanent vision loss from corneal scarring, perforation or endophthalmitis. An infectious corneal ulcer requires immediate treatment with intensive topical fortified broad-spectrum antibiotics to try to eliminate the pathogen. Corneal tissue destruction can be caused directly by infectious agents, the associated inflammatory response, or by ocular toxicity from frequent dosing of fortified antibiotics.1 Sutured amniotic membrane transplantation (AMT) has been shown to reduce pain and promote healing in human bacterial keratitis.2 ProKera® is a sutureless form of CryoTek amniotic membrane that is clipped into a dual polycarbonate ring system with the epithelial side up when in contact with the ocular surface. ProKera Plus® contains a double layer of CryoTek amniotic membrane tissue to provide extra therapeutic benefit. ProKera Plus® has several advantages over sutured AMT including ease of administration in a clinic setting and reduced overall procedural cost. The role of ProKera® in the treatment algorithm of corneal ulcers has yet to be fully clarified. There are currently no prospective case studies comparing the use of ProKera® to standard of care conventional treatments in corneal ulcers. The utility of this device would provide valuable information in the treatment of bacterial corneal ulcers. The objectives are: To determine if ProKera Plus® can lead to better visual recovery when used with bacterial corneal ulcers compared to conventional treatment To determine if ProKera Plus® can actively modify corneal wound healing during the course of managing bacterial corneal ulcers and decrease the overall time to re-epithelialization To determine if ProKera Plus® can decrease pain associated with bacterial corneal ulcers compared to conventional treatment To determine if ProKera Plus® can decrease the amount of corneal opacity and corneal thinning associated with bacterial corneal ulcers compared to conventional treatment To determine if ProKera Plus® can decrease the need for further interventions or surgeries related to complications from bacterial corneal ulcers

Official Title
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A Prospective, Randomized, Controlled Clinical Study to Evaluate the Use of ProKera Plus® in the Management of Bacterial Corneal Ulcers

Conditions
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Bacterial Corneal Ulcer

Intervention / Treatment
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* Device: ProProKera Plus®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria Subjects 18 years of age or older, all sexes and races Willing to sign a written informed consent to participate Corneal ulcer criteria: at least 3mm in diameter, opacification located within 3mm of visual axis, infiltrate occupying at least 50% of the corneal thickness, moderate AC cell reaction, clinical picture consistent with bacterial infection later confirmed by culture and gram stain. Exclusion Criteria: History of Immunodeficiency History of connective tissue disorders or severe atopic disease History of chemical eye injuries History of known limbal stem cell deficiency History of neurotrophic keratopathy History of recent eye surgery, or glaucoma surgery with bleb or drainage tube Risk factors and clinical appearance consistent with fungal keratitis

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Phase 1: This phase will establish baseline characteristics for each patient that is randomized into the treatment arm for the phase 2 part of the study. Phase 2: This phase will test the intervention of using ProKera Plus® versus continuing conventional treatment for the corneal ulcer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional Treatment<br>Corneal ulcer scraping sent for microbial culture Admission to the hospital for initiation of fortified vancomycin 25mg/mL every 1 hour alternating with fortified tobramycin 15mg/mL every 1 hour, preservative free artificial tears every 2 hours, and doxycycline 100mg twice daily. After 48 hours of conventional treatment, consent will be obtained regarding the use of experimental treatment with ProKera Plus® versus continuing conventional method of treatment | |
| Experimental: ProKera Plus® Treatment<br>1. Experimental Treatment Arm , ProKera Plus® will be placed in the eye with the corneal ulcer | Device: ProProKera Plus®<br>* ProKera® is a sutureless form of CryoTek amniotic membrane that is clipped into a dual polycarbonate ring system with the epithelial side up when in contact with the ocular surface.<br>* Other names: ProKera Plus®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity - Visit 1 | Visual acuity (VA) was assessed for participants applicable study eye using a Snellen letter chart. VA was collected in Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with lower logMAR values indicating better visual acuity. | 5-day Follow-Up, plus or minus 3 days | 
| Visual Recovery - Visit 2 | Visual acuity (VA) was assessed for participants applicable study eye using a Snellen letter chart. VA was collected in Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with lower logMAR values indicating better visual acuity. | 16-day follow-up plus or minus 5 days | 
| Visual Recovery - Visit 3 | Visual acuity (VA) was assessed for participants applicable study eye using a Snellen letter chart. VA was collected in Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with lower logMAR values indicating better visual acuity. | 30-day follow-up plus or minus 7 days | 
| Visual Recovery - Visit 4 | Visual acuity (VA) was assessed for participants applicable study eye using a Snellen letter chart. VA was collected in Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with lower logMAR values indicating better visual acuity. | 90 day follow-up plus or minus 10 days | 
| Visual Recovery - Visit 5 | Visual acuity (VA) was assessed for participants applicable study eye using a Snellen letter chart. VA was collected in Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with lower logMAR values indicating better visual acuity. | 180-day follow-up plus or minus 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal Re-epithelialization - Visit 1 | number of participants who had slit lamp photography which measured fluorescein staining size. | 5-day follow-up plus or minus 3 days | 
| Corneal Re-epithelialization - Visit 2 | number of participants who had slit lamp photography which measured fluorescein staining size. | 16-day follow-up plus or minus 5 days | 
| Corneal Re-epithelialization - Visit 3 | number of participants who had slit lamp photography which measured fluorescein staining size. | 30-day follow-up plus or minus 7 days | 
| Corneal Re-epithelialization - Visit 4 | number of participants who had slit lamp photography which measured fluorescein staining size. | 90-day follow-up plus or minus 10 days | 
| Corneal Opacity Size - Visit 1 | number of participants who had anterior segment optical coherence tomography (ASOCT). | 5-day follow-up plus or minus 3 days | 
| Corneal Opacity Size - Visit 3 | number of participants who had anterior segment optical coherence tomography (ASOCT). | 30-day follow-up plus or minus 7 days | 
| Corneal Opacity Thinning-Visit 1 | number of participants who had anterior segment optical coherence tomography (ASOCT). | 5-day follow-up plus or minus 3 days | 
| Corneal Opacity Thinning-Visit 3 | number of participants who had anterior segment optical coherence tomography (ASOCT). | 30-day follow-up plus or minus 7 days | 
| Eye Pain- Visit 1 | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) | 5-day follow-up plus or minus 3 days | 
| Eye Pain- Visit 2 | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) | 16-day follow-up plus or minus 5 days | 
| Eye Pain- Visit 3 | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) | 30-day follow-up plus or minus 7 days | 
| Eye Pain- Visit 4 | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) | 90-day follow-up plus or minus 10 days | 
| Eye Pain- Visit 5 | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) | 180-day follow-up plus or minus 14 days |