Bacterial Corneal Ulcer
Conditions
Brief summary
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
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: 1. To determine if ProKera Plus® can lead to better visual recovery when used with bacterial corneal ulcers compared to conventional treatment 2. 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 3. To determine if ProKera Plus® can decrease pain associated with bacterial corneal ulcers compared to conventional treatment 4. To determine if ProKera Plus® can decrease the amount of corneal opacity and corneal thinning associated with bacterial corneal ulcers compared to conventional treatment 5. To determine if ProKera Plus® can decrease the need for further interventions or surgeries related to complications from bacterial corneal ulcers
Interventions
DEVICEProProKera Plus®
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.
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity - Visit 1 | 5-day Follow-Up, plus or minus 3 days | 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. |
| Visual Recovery - Visit 2 | 16-day follow-up plus or minus 5 days | 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. |
| Visual Recovery - Visit 3 | 30-day follow-up plus or minus 7 days | 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. |
| Visual Recovery - Visit 4 | 90 day follow-up plus or minus 10 days | 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. |
| Visual Recovery - Visit 5 | 180-day follow-up plus or minus 14 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Corneal Opacity Size - Visit 3 | 30-day follow-up plus or minus 7 days | number of participants who had anterior segment optical coherence tomography (ASOCT). |
| Corneal Opacity Thinning-Visit 1 | 5-day follow-up plus or minus 3 days | number of participants who had anterior segment optical coherence tomography (ASOCT). |
| Corneal Opacity Thinning-Visit 3 | 30-day follow-up plus or minus 7 days | number of participants who had anterior segment optical coherence tomography (ASOCT). |
| Eye Pain- Visit 1 | 5-day follow-up plus or minus 3 days | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) |
| Corneal Re-epithelialization - Visit 2 | 16-day follow-up plus or minus 5 days | number of participants who had slit lamp photography which measured fluorescein staining size. |
| Eye Pain- Visit 3 | 30-day follow-up plus or minus 7 days | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) |
| Eye Pain- Visit 4 | 90-day follow-up plus or minus 10 days | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) |
| Eye Pain- Visit 5 | 180-day follow-up plus or minus 14 days | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) |
| Eye Pain- Visit 2 | 16-day follow-up plus or minus 5 days | Average pain rating across participants which was assessed subjectively using the Visual Analog Scale (VAS) ranging from 0 (none) to 10 (worst possible pain) |
| Corneal Re-epithelialization - Visit 1 | 5-day follow-up plus or minus 3 days | number of participants who had slit lamp photography which measured fluorescein staining size. |
| Corneal Re-epithelialization - Visit 3 | 30-day follow-up plus or minus 7 days | number of participants who had slit lamp photography which measured fluorescein staining size. |
| Corneal Re-epithelialization - Visit 4 | 90-day follow-up plus or minus 10 days | number of participants who had slit lamp photography which measured fluorescein staining size. |
| Corneal Opacity Size - Visit 1 | 5-day follow-up plus or minus 3 days | number of participants who had anterior segment optical coherence tomography (ASOCT). |
Countries
United States
Participant flow
Recruitment details
Total number of candidates screened and enrolled in study was 3. The goal of the study was to enroll 24 subjects, 12 subjects per group. Patients were recruited in the medical clinic (UAMS). recruitment started in November 2021 and ended in March 2022.
Pre-assignment details
After at least 48 hours of conventional treatment, consent will be obtained regarding the use of experimental treatment with Prokera Plus versus continuing conventional treatment. This will be randomized in a 1:1 ratio by a block-randomization schedule to assign subjects to each of the two treatment groups. All three subjects that were screened were consented and assigned a group.
Participants by arm
| Arm | Count |
|---|---|
| Conventional Treatment * 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 | 1 |
| ProKera Plus® Treatment 1\. Experimental Treatment Arm , ProKera Plus® will be placed in the eye with the corneal ulcer
ProProKera Plus®: 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. | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | ProKera Plus® Treatment | Total | Conventional Treatment |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
| Vision Acuity at Baseline | 1.45 LogMAR STANDARD_DEVIATION 0.45 | 1.6 LogMAR STANDARD_DEVIATION 0.424 | 1.9 LogMAR |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 2 / 2 |
Outcome results
Primary
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.
Time frame: 5-day Follow-Up, plus or minus 3 days
Population: All randomized subjects regardless of actual treatment, with data at the 5-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Treatment | Visual Acuity - Visit 1 | 1.3 LogMar | — |
| ProKera Plus® Treatment | Visual Acuity - Visit 1 | 3.3 LogMar | Standard Deviation 0.65 |
Primary
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.
Time frame: 16-day follow-up plus or minus 5 days
Population: All randomized subjects regardless of actual treatment, with data at the 16-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Treatment | Visual Recovery - Visit 2 | 1.3 LogMar | — |
| ProKera Plus® Treatment | Visual Recovery - Visit 2 | 2.1 LogMar | Standard Deviation 0.2 |
Primary
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.
Time frame: 30-day follow-up plus or minus 7 days
Population: All randomized subjects regardless of actual treatment, with data at the 30-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Treatment | Visual Recovery - Visit 3 | 0.6 LogMar | — |
| ProKera Plus® Treatment | Visual Recovery - Visit 3 | 2.1 LogMar | Standard Deviation 0.2 |
Primary
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.
Time frame: 90 day follow-up plus or minus 10 days
Population: All randomized subjects regardless of actual treatment, with data at the 90-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Conventional Treatment | Visual Recovery - Visit 4 | .47 LogMar |
| ProKera Plus® Treatment | Visual Recovery - Visit 4 | .70 LogMar |
Primary
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.
Time frame: 180-day follow-up plus or minus 14 days
Population: All randomized subjects regardless of actual treatment, with data at the 180-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Conventional Treatment | Visual Recovery - Visit 5 | .6 LogMar |
| ProKera Plus® Treatment | Visual Recovery - Visit 5 | 1 LogMar |
Secondary
Corneal Opacity Size - Visit 1
number of participants who had anterior segment optical coherence tomography (ASOCT).
Time frame: 5-day follow-up plus or minus 3 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Treatment | Corneal Opacity Size - Visit 1 | 1 Participants |
| ProKera Plus® Treatment | Corneal Opacity Size - Visit 1 | 1 Participants |
Secondary
Corneal Opacity Size - Visit 3
number of participants who had anterior segment optical coherence tomography (ASOCT).
Time frame: 30-day follow-up plus or minus 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Treatment | Corneal Opacity Size - Visit 3 | 0 Participants |
| ProKera Plus® Treatment | Corneal Opacity Size - Visit 3 | 2 Participants |
Secondary
Corneal Opacity Thinning-Visit 1
number of participants who had anterior segment optical coherence tomography (ASOCT).
Time frame: 5-day follow-up plus or minus 3 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Treatment | Corneal Opacity Thinning-Visit 1 | 1 Participants |
| ProKera Plus® Treatment | Corneal Opacity Thinning-Visit 1 | 1 Participants |
Secondary
Corneal Opacity Thinning-Visit 3
number of participants who had anterior segment optical coherence tomography (ASOCT).
Time frame: 30-day follow-up plus or minus 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Treatment | Corneal Opacity Thinning-Visit 3 | 0 Participants |
| ProKera Plus® Treatment | Corneal Opacity Thinning-Visit 3 | 1 Participants |
Secondary
Corneal Re-epithelialization - Visit 1
number of participants who had slit lamp photography which measured fluorescein staining size.
Time frame: 5-day follow-up plus or minus 3 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Treatment | Corneal Re-epithelialization - Visit 1 | 0 participants |
| ProKera Plus® Treatment | Corneal Re-epithelialization - Visit 1 | 1 participants |
Secondary
Corneal Re-epithelialization - Visit 2
number of participants who had slit lamp photography which measured fluorescein staining size.
Time frame: 16-day follow-up plus or minus 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Treatment | Corneal Re-epithelialization - Visit 2 | 1 participants |
| ProKera Plus® Treatment | Corneal Re-epithelialization - Visit 2 | 2 participants |
Secondary
Corneal Re-epithelialization - Visit 3
number of participants who had slit lamp photography which measured fluorescein staining size.
Time frame: 30-day follow-up plus or minus 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Treatment | Corneal Re-epithelialization - Visit 3 | 1 Participants |
| ProKera Plus® Treatment | Corneal Re-epithelialization - Visit 3 | 2 Participants |
Secondary
Corneal Re-epithelialization - Visit 4
number of participants who had slit lamp photography which measured fluorescein staining size.
Time frame: 90-day follow-up plus or minus 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Treatment | Corneal Re-epithelialization - Visit 4 | 0 Participants |
| ProKera Plus® Treatment | Corneal Re-epithelialization - Visit 4 | 1 Participants |
Secondary
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)
Time frame: 5-day follow-up plus or minus 3 days
Population: All randomized subjects regardless of actual treatment, with data at the 5-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Treatment | Eye Pain- Visit 1 | 10 score on a scale | — |
| ProKera Plus® Treatment | Eye Pain- Visit 1 | 2.5 score on a scale | Standard Deviation 1.5 |
Secondary
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)
Time frame: 16-day follow-up plus or minus 5 days
Population: All randomized subjects regardless of actual treatment, with data at the 16-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Treatment | Eye Pain- Visit 2 | 1 units on a scale | — |
| ProKera Plus® Treatment | Eye Pain- Visit 2 | 1.7 units on a scale | Standard Deviation 1.7 |
Secondary
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)
Time frame: 30-day follow-up plus or minus 7 days
Population: All randomized subjects regardless of actual treatment, with data at the 30-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Treatment | Eye Pain- Visit 3 | 0 units on a scale | — |
| ProKera Plus® Treatment | Eye Pain- Visit 3 | 2 units on a scale | Standard Deviation 2 |
Secondary
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)
Time frame: 90-day follow-up plus or minus 10 days
Population: All randomized subjects regardless of actual treatment, with data at the 90-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Conventional Treatment | Eye Pain- Visit 4 | 2 units on a scale |
| ProKera Plus® Treatment | Eye Pain- Visit 4 | 0 units on a scale |
Secondary
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)
Time frame: 180-day follow-up plus or minus 14 days
Population: All randomized subjects regardless of actual treatment, with data at the 180-day Follow-up Evaluation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Conventional Treatment | Eye Pain- Visit 5 | 0 units on a scale |
| ProKera Plus® Treatment | Eye Pain- Visit 5 | 0 units on a scale |