This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Evaluating the Use of ProKera Plus® in the Management of Bacterial Corneal Ulcers (NCT04850313), a randomized na study. The primary outcome is Visual Acuity - Visit 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04850313 |
| Phase | NA |
| Condition | Bacterial Corneal Ulcer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Arkansas |
| Results posted | Yes |
2. Clinical Question
Population
People with vision-threatening bacterial corneal ulcers presenting to an Ophthalmology clinic or Emergency Department at the University of Arkansas Medical Sciences were the intended population. The registry reports enrollment of 3 participants. The primary endpoint population was all randomized subjects regardless of actual treatment, with data at the 5-day follow-up evaluation.
Intervention
The experimental arm received ProKera Plus® placed in the eye with the corneal ulcer. The intervention is identified as a device. The registry does not report further procedural detail for placement or describe the treatment schedule beyond that statement.
Comparator
The comparator was conventional treatment. The description includes corneal ulcer scraping for microbial culture, hospital admission, fortified vancomycin and tobramycin, preservative-free artificial tears, and doxycycline. It also includes the phrase “After 48 hours,” but the remainder of that description is not reported in the registry record.
Primary question
The study set out to compare visual acuity at the first visit, measured at a 5-day follow-up with a window of plus or minus 3 days. The registry reports the arm-level means but no estimable two-arm comparison. The posted numbers therefore describe the recorded participants rather than establish a comparative treatment effect.
The intended design was prospective, randomized, and controlled, with parallel arms. The study description says it was to compare ProKera Plus® with conventional treatment in patients with bacterial corneal ulcers. The registry does not provide a detailed statement of the primary hypothesis or a prespecified threshold for a meaningful visual-acuity change. It also does not report a sample-size justification. Those details cannot be inferred from the small number enrolled or from the outcome data.
3. Trial Design
This was a randomized, controlled, parallel-group interventional study with no masking. The registry lists the phase as NA. It identifies the University of Arkansas as sponsor and University of Arkansas Medical Sciences as the study location in the summary. Enrollment was 3. The study started on 2021-11-09, reached primary completion on 2022-09-30, and has a status of terminated. The reason for termination is not reported in the registry record.
The registry describes two arms: conventional treatment and ProKera Plus® treatment. In the ProKera Plus® arm, the device was to be placed in the eye with the ulcer. The conventional-treatment description includes corneal scraping for microbial culture and hospital admission for treatment with fortified antibiotics, artificial tears, and doxycycline. Its description ends with “After 48 hours” without specifying what followed, so the full treatment protocol cannot be reconstructed from the record.
The brief study description refers to conducting the study in two phases, but the phases and their procedures are not described in enough detail to characterize them. The record does not report how the randomization sequence was generated, how allocation was concealed, or whether any steps were taken to standardize care across participants. It identifies the study as unmasked, so participants and study personnel were not reported as blinded.
The planned primary endpoint was visual acuity at the first visit, with assessment at the 5-day follow-up, plus or minus 3 days. The registry gives means for the arms but does not report a usable inferential comparison. The actual number of participants with primary endpoint data in each arm is indicated by the outcome records: 1 in conventional treatment and 2 in ProKera Plus® treatment. The record does not explain why the study was terminated or give a fuller account of participant disposition.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 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.
Overall Study
| Stage | Conventional Treatment | ProKera Plus® Treatment |
|---|---|---|
| STARTED | 1 | 2 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Conventional Treatment | ProKera Plus® Treatment |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All randomized subjects regardless of actual treatment, with data at the 5-day Follow-up Evaluation.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Conventional Treatment | ProKera Plus® Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 2 | 3 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 2 | 3 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Vision Acuity at Baseline | LogMAR | 1.9 (SD NA) | 1.45 (SD .45) | 1.6 (SD .424) |
6. Primary Endpoint
The registry lists the primary outcome as Visual Acuity - Visit 1, measured over 5-day Follow-Up, plus or minus 3 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | LogMar |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was visual acuity at Visit 1, assessed at the 5-day follow-up, plus or minus 3 days. Visual acuity was assessed for the applicable study eye with a Snellen letter chart and converted from Snellen notation to logarithm minimum angle of resolution, or logMAR. The outcome is reported as a mean, with standard deviation as the stated measure of dispersion.
The registry explains the direction of the scale: a logMAR value of 0 equates to 20/20 Snellen visual acuity, and lower logMAR values indicate better visual acuity. This makes the endpoint a quantitative measure of visual acuity that can be summarized across participants. It is relevant to a study of corneal ulcers because visual acuity records an aspect of vision, while the listed secondary outcomes include measures of corneal re-epithelialization and opacity.
The endpoint population was defined as all randomized subjects regardless of actual treatment, provided they had data at the 5-day follow-up evaluation. That definition uses the randomized groups for attribution but requires an observed follow-up measurement. The record does not report how many randomized participants lacked a measurement or how missing measurements were handled. It also does not provide a threshold for interpreting a change in logMAR as clinically important. The endpoint values therefore describe measured visual acuity; they do not, by themselves, establish the clinical importance of an arm difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For visual acuity at Visit 1, the conventional-treatment arm had a mean logMAR value of 1.3 among 1 participant. The ProKera Plus® arm had a mean of 3.3 among 2 participants, with a standard deviation of 0.65. The registry defines lower logMAR values as better visual acuity. These are descriptive summaries from the participants with endpoint data; they should not be read as a reliable estimate of a treatment effect.
The evidence is especially limited because the conventional-treatment mean is based on one participant, and the registry reports no standard deviation for that arm. A single observation cannot characterize variation among participants in that group. Although a standard deviation is reported for the two participants in the ProKera Plus® arm, that estimate is also based on very few observations. The record reports no confidence interval, p-value, or other inferential result for the primary endpoint.
The registry indicates that values were missing or not estimable for a two-arm comparison of this continuous endpoint. Accordingly, it does not give a formal estimate of the between-arm difference or its uncertainty. The arm means can be read as recorded values, but the numerical separation between them should not be turned into a conclusion about comparative effectiveness. The study’s randomized design does not overcome the lack of an estimable comparison in the posted results.
The safety record lists serious adverse events for 2 of 2 participants at risk in the ProKera Plus® arm and 0 of 1 in the conventional-treatment arm. The leading serious adverse-event term is Corneal Melt, listed as 100.0%. There were no deaths reported, and no other adverse events were reported as affecting participants in either arm. These counts describe what was recorded in a trial with very few participants; they do not provide a precise estimate of event frequency or a robust comparison between treatments.
The registry reports 18 outcome measures and 13 posted secondary outcomes, but lists zero analyses. This distinction matters: outcome measures may be specified or collected without a corresponding analysis result being available. The record does not give enough information to assess how completely outcomes were measured, how secondary results were selected for posting, or whether all planned analyses were performed. The reason for termination is also not reported. Taken together, the posted data offer a small descriptive record, not a conclusive comparative assessment.
9. Statistical Methods Explained
What does a mean and standard deviation describe?
A mean is the arithmetic average of the recorded values in a group. For a continuous endpoint such as logMAR visual acuity, it provides a compact description of the group’s measured values. A standard deviation describes how spread out the observations are around their mean. It is a measure of variability among observed values, not a measure of uncertainty in the treatment comparison.
In this study, the conventional-treatment mean is 1.3 based on 1 participant, and no standard deviation is reported for that arm. The ProKera Plus® mean is 3.3 based on 2 participants, with a standard deviation of 0.65. With so few observations, these summaries are highly dependent on the measured values of the individual participants. The conventional group’s single observation cannot show how much participant-to-participant variability exists in that arm. The standard deviation reported for the ProKera Plus® group also has limited ability to characterize variability.
Why is the arm comparison not estimated?
A comparative analysis of a continuous outcome generally needs information about both groups, including a measure of variability, to quantify the difference and its uncertainty. The registry states that values were missing or not estimable for a two-arm comparison. It therefore does not report a comparative estimate, confidence interval, or p-value for the primary endpoint. The group means remain descriptive statistics; the record does not support treating their difference as a formal treatment-effect estimate.
A confidence interval, as a general statistical concept, expresses a range of values compatible with the data and the assumptions of the analysis. Its width reflects precision: wider intervals indicate less precise estimation. No confidence interval is reported for the primary endpoint in this record, so the precision of a between-arm effect cannot be read from an interval. The absence of an interval is not evidence that the groups are equivalent; it means the registry does not provide that inferential result.
How should the logMAR scale be read?
The outcome was converted from Snellen visual acuity to logMAR. The registry states that 0 corresponds to 20/20 Snellen visual acuity and that lower logMAR values indicate better visual acuity. Thus, the direction of the scale is important when reading arm means: a larger value does not indicate better acuity on this scale. This general interpretation does not resolve the limitations of the observed comparison, which has very few participants and no reported inferential analysis.
What does randomization contribute?
Random assignment is intended, in general, to make treatment groups comparable with respect to both measured and unmeasured characteristics at the point of allocation. It supports a causal comparison when the trial is implemented as planned and when outcome data and analysis are adequate. The registry identifies the study as randomized, but it does not report how the allocation sequence was generated or concealed. With enrollment of 3, randomization cannot ensure that this particular small set of participants was balanced in relevant characteristics. The record also identifies the study as unmasked, which means the design does not report masking of participants or study personnel.
What can planning calculations tell readers?
Sample-size calculations are planning tools. In general, they describe how many participants might be needed under assumptions about the effect to detect, variability, significance level, allocation, and statistical model. They are not evidence that a trial had a particular probability of detecting an effect after the data have been collected. A sample-size illustration based on an observed effect is also not observed power and does not replace a confidence interval or an appropriate treatment-effect estimate.
The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning convention is total events; for other outcomes, it is participants per arm. These are assumptions for planning illustrations, not a report of the trial’s original design rationale. The trial’s sample-size justification is not reported in the registry record. In particular, the record does not establish that enrollment of 3 was the intended target or explain whether the study stopped before a planned enrollment was reached.
How do multiplicity and multiple outcomes matter?
When a study assesses multiple outcomes or performs multiple statistical tests, the chance of at least one apparently unusual result can increase. Statistical methods may address this issue by designating a primary endpoint, adjusting the interpretation of multiple tests, or clearly separating confirmatory from exploratory analyses. These are general considerations; the registry does not report a multiplicity adjustment or a detailed hierarchy for interpreting outcomes.
The record lists 18 outcome measures, 13 posted secondary outcomes, and zero analyses. The primary endpoint is identified as visual acuity at Visit 1, while the secondary outcomes include repeated assessments of corneal re-epithelialization and opacity. The registry does not explain the relationship between the listed outcomes, the posted secondary results, and the analyses performed. Without that information, readers cannot determine whether all intended analyses were completed or how the selection of reported secondary results was managed.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies visual acuity at Visit 1 as the primary endpoint and lists 18 outcome measures overall. It counts 13 secondary outcomes as posted, while listing zero analyses. The record does not explain which analyses correspond to the posted secondary outcomes or whether every planned outcome was analyzed. It also does not report a statistical method for controlling multiplicity or a hierarchy for interpreting the many outcome measures. When multiple endpoints are considered, this missing context makes it difficult to distinguish confirmatory findings from exploratory descriptions.
The primary endpoint population is described as all randomized subjects regardless of actual treatment, with data at the 5-day follow-up evaluation. This indicates that the reported endpoint summaries include participants with a measurement at that visit. The arm records contain data for 1 conventional-treatment participant and 2 ProKera Plus® participants. The registry does not report the number of randomized participants without endpoint data, reasons for missing measurements, or a method for handling missing data. It does not describe imputation, sensitivity analyses, or other procedures for assessing whether missingness could affect the interpretation.
The record also does not specify whether analyses followed an intention-to-treat principle beyond its description of the endpoint population, or whether any per-protocol or other analysis populations were used. The wording “regardless of actual treatment” describes the intended population definition, but does not by itself establish how every participant was handled in an analysis. Given the very small enrollment and the absence of a reported comparative analysis, these gaps prevent assessment of the consequences of missing data and of selective outcome reporting.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Conventional Treatment | 0 | 1 | 0.0% |
| ProKera Plus® Treatment | 2 | 2 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Conventional Treatment | 0 of 1 |
| ProKera Plus® Treatment | 0 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Conventional Treatment | 0 of 1 |
| ProKera Plus® Treatment | 0 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Conventional Treatment | ProKera Plus® Treatment |
|---|---|---|---|
| Corneal Melt | Eye disorders | 0 of 1 | 2 of 2 |
Serious events with the highest arm-level rate: corneal melt (100.0%).
The serious adverse-event counts are 0 of 1 participant at risk in the conventional-treatment arm and 2 of 2 participants at risk in the ProKera Plus® arm. The registry lists Corneal Melt as the leading serious adverse-event term, with 100.0%. It reports no deaths in either arm. For other adverse events, 0 of 1 conventional-treatment participants and 0 of 2 ProKera Plus® participants are listed as affected.
These are counts from a very small study. They document the events recorded in the enrolled groups, but they do not provide precise estimates of how frequently such events would occur in a broader population. The arms also differ in the number of participants at risk, so the raw counts should not be treated as a dependable comparative safety estimate. The record does not give additional detail about event timing, severity beyond the serious classification, relatedness to treatment, or the criteria used to attribute events. The serious-event figures therefore warrant cautious, descriptive reading and cannot establish a general safety profile.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry contains visual-acuity summaries at the 5-day follow-up for participants in both randomized arms. The conventional-treatment mean is 1.3 for 1 participant. The ProKera Plus® mean is 3.3 for 2 participants, with a standard deviation of 0.65. The registry explains that lower logMAR values indicate better visual acuity. It also states that the values were missing or not estimable for a two-arm comparison, so there is no reported estimate of the treatment contrast or its precision.
These data do not establish that either treatment improves visual acuity, nor do they establish that the treatments are equivalent. A descriptive difference between group means is not the same as an estimated treatment effect with quantified uncertainty. The sample is too small to support a stable generalization, and the registry provides no inferential result for the primary comparison. The record does not report a threshold for a clinically important difference, which further limits interpretation of the observed values.
The safety counts document serious adverse events among the participants recorded in each arm, including the listed Corneal Melt term. Because there were only 3 participants enrolled, the figures cannot provide a precise estimate of safety risks or a reliable comparison. No deaths are recorded, and no other adverse events are listed as affecting participants. Those records describe what was posted, not what would necessarily occur in a larger group.
The study status is terminated, but the reason is not reported in the registry record. Without that explanation, the termination cannot be attributed to the observed outcomes, recruitment, logistics, or any other cause. Overall, the results should be read as a limited descriptive account from a very small randomized study. They do not provide a conclusive answer to the comparative clinical question.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical research: having a randomized design does not guarantee that the final data will support an informative treatment comparison. Randomization is a valuable design feature, but its potential benefits depend on having sufficient observations and outcome data to estimate the contrast with useful precision. Here, enrollment was 3, and the registry reports primary-endpoint data for 1 participant in the conventional-treatment arm and 2 in the ProKera Plus® arm.
The record also makes clear why descriptive summaries and inferential results should not be conflated. Means are reported, but the registry says a two-arm comparison of the continuous endpoint was not estimable. There is no reported confidence interval or p-value. A reader can describe the recorded values and the direction of the logMAR scale, but cannot use those summaries to establish a treatment effect or its precision.
The trial also highlights the importance of transparent reporting around termination, missing data, and analysis plans. The status is terminated, but the reason is not reported. The registry does not explain missing measurements, the handling of missing data, or how the planned outcome family was managed. Such information is important for understanding how far the posted results can answer the original question.
Finally, the serious adverse-event counts show why small safety datasets require careful interpretation. Counts can be important for documenting what occurred, while remaining too sparse for stable estimates of event frequency or comparative risk. The study is statistically instructive because it demonstrates how design labels, outcome summaries, inferential evidence, and precision are separate parts of evaluating clinical trial evidence.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The central limitation is the very small enrollment: 3 participants. The primary outcome summaries are based on 1 participant in the conventional-treatment arm and 2 in the ProKera Plus® arm. With so few observations, group averages and variability estimates are highly sensitive to individual measurements, and the data cannot support a precise general comparison.
The registry explicitly states that values were missing or not estimable for a two-arm comparison of the continuous primary endpoint. It provides no effect estimate, confidence interval, or p-value. The conventional-treatment arm has no reported standard deviation. These omissions prevent assessment of the size and uncertainty of a between-arm difference. The record also does not explain why the comparison was not estimable.
The study was unmasked, and the registry does not report allocation-sequence generation or concealment. It does not give details on participant flow, missing endpoint data, or missing-data methods. The study is marked terminated, but the reason is not reported. Its primary endpoint is measured at the 5-day follow-up, plus or minus 3 days; the record does not provide longer-term primary visual-acuity results.
Additional limitations concern protocol detail and reporting. The conventional-treatment description is incomplete after “After 48 hours,” and the statement that the study would be conducted in two phases is not accompanied by a description of those phases. The registry lists many outcome measures but no analyses, and does not report a multiplicity strategy, a sample-size justification, or a detailed statistical plan. These gaps make it difficult to assess how closely the posted results reflect the full intended study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluating the Use of ProKera Plus® in the Management of Bacterial Corneal Ulcers — NCT04850313.
- Registry record last updated 2023-07-07; status last verified 2023-03.
- Results first posted 2023-07-07.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT04850313 is a prospective, randomized, controlled, parallel-group study of ProKera Plus® versus conventional treatment for bacterial corneal ulcers. It was unmasked, sponsored by the University of Arkansas, and listed as terminated. Enrollment was 3. The study began on 2021-11-09, with primary completion on 2022-09-30.
The primary outcome was visual acuity at Visit 1, assessed at the 5-day follow-up, plus or minus 3 days, and reported in logMAR. The registry reports a mean of 1.3 for 1 conventional-treatment participant and a mean of 3.3 with standard deviation 0.65 for 2 ProKera Plus® participants. It reports no estimable two-arm comparison. Serious adverse events affected 0 of 1 conventional-treatment participants and 2 of 2 ProKera Plus® participants; no deaths were reported. The reason for termination and the trial’s sample-size justification are not reported in the registry record.