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 Sterile Amniotic Fluid Filtrate Epidural Injection. (NCT04537026), a randomized phase 1, phase 2 study. The primary outcome is The Percentage of Participants Reporting >50% Improvement in the Numeric Rating Scale Pain Score at 3 Months; Back and Leg Pain Separately..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04537026 |
| Phase | Phase 1, Phase 2 |
| Condition | Lumbar Spinal Stenosis |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 58 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
People with lumbosacral radicular pain due to lumbar spinal stenosis were the focus. The study rationale describes people whose symptoms have not responded to physical therapy or oral medication management, and who wish to avoid spinal surgery or are not candidates for it because of medical co-morbidity. The registry record does not report further eligibility criteria or the characteristics of participants enrolled.
Intervention
The intervention was transforaminal epidural amniotic fluid injection, described in the record as amniotic fluid allograft. The study rationale refers to human amniotic fluid, abbreviated hAF, and proposes it as a biologic treatment with anti-inflammatory, neuro-protective, and regenerative properties. Those proposed properties are part of the rationale, not findings established by the registry results.
Comparator
The comparator was transforaminal epidural dexamethasone injection. The record describes this as dexamethasone sodium phosphate and identifies corticosteroid injection as the typical treatment for the population discussed in the rationale. The registry record does not report comparative outcome estimates.
Primary question
The primary question was whether the proportion of participants reporting >50% improvement in Numeric Rating Scale pain score at 3 months differed between the injection approaches, with back and leg pain considered separately. The record describes categorical pain and function measures as the basis for the primary outcome analysis, citing recent recommendations by the National Institute of Health. No primary outcome analysis is reported in the registry record.
3. Trial Design
This was a Phase I/II randomized, triple-masked, prospective study with a crossover model. The registry record lists 58 participants as the enrollment and identifies University of Utah as the sponsor. Its status is completed; the recorded study start is 2021-06-16 and the primary completion date is 2025-07-01. These design and administrative details describe how the study was organized, but do not establish whether the interventions differed in outcome.
The comparison was between transforaminal epidural amniotic fluid injection and transforaminal epidural dexamethasone injection. Both arm descriptions begin with fluoroscopic guidance and describe an epidural injection, but the available descriptions are truncated. Further procedural details are not reported in the registry record. The crossover designation indicates that the study design involved participants receiving treatments in a sequence, but the sequence, timing, and any washout arrangements are not reported in the registry record.
Triple masking means that the registry classifies the study as masked at three levels, but the identities of the masked groups and how masking was maintained are not reported in the registry record. The record also does not report the randomization procedure, allocation concealment, or whether masking was assessed. These omissions prevent a detailed appraisal of how assignment and expectations may have been managed.
The primary endpoint was a categorical improvement measure at 3 months, with back and leg pain assessed separately. Listed secondary outcomes include mean change in back and leg Numeric Pain Rating Scale scores, Oswestry Disability Index measures, and Swiss Spinal Stenosis Questionnaire measures. The broader study rationale also names psychological function, oral analgesic use, and avoidance of surgery as outcomes of interest. The registry record does not report analysis results for these outcomes.
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.
Overall Study
| Stage | Transforaminal Epidural Amniotic Fluid Injection | Transforaminal Epidural Dexamethasone Injection |
|---|---|---|
| STARTED | 28 | 30 |
| COMPLETED | 27 | 29 |
| NOT COMPLETED | 1 | 1 |
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 | Transforaminal Epidural Amniotic Fluid Injection | Transforaminal Epidural Dexamethasone Injection | Total |
|---|---|---|---|---|
| Participants analysed | 28 | 30 | 58 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 18 | 18 | 36 |
| Age, Categorical: >=65 years | Participants | 10 | 12 | 22 |
| Age, Continuous | years | 56.6 (SD 15.9) | 56.7 (SD 14.9) | 56.65 (SD 15.4) |
| Sex: Female, Male: Female | Participants | 14 | 21 | 35 |
| Sex: Female, Male: Male | Participants | 14 | 9 | 23 |
| Race/Ethnicity, Customized: Hispanic | Participants | 3 | 1 | 4 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: White | Participants | 25 | 28 | 53 |
| Race/Ethnicity, Customized: Unknown | Participants | 2 | 0 | 2 |
| Region of Enrollment: United States | participants | 28 | 30 | 58 |
6. Primary Endpoint
The registry lists the primary outcome as The Percentage of Participants Reporting >50% Improvement in the Numeric Rating Scale Pain Score at 3 Months; Back and Leg Pain Separately., measured over 3 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants reporting >50% improvement in Numeric Rating Scale pain score at 3 months. Back pain and leg pain are specified separately, so the endpoint is not a single combined score. It is a categorical outcome: participants are classified according to whether they meet the improvement threshold, and the measure concerns the proportion in each category rather than the average change in pain score.
A threshold-based endpoint can make a result easier to interpret in terms of how many participants reached a specified degree of improvement. It also discards information about the size of changes within each category: participants just below and just above the threshold are treated differently even if their scores are close, while participants with different degrees of improvement beyond the threshold are grouped together. Those are general properties of categorizing a continuous measure, not findings about this trial.
The record says categorical measures of pain and function were chosen for the primary outcome analysis in light of recent recommendations by the National Institute of Health. The registry record does not report the actual number or percentage meeting the threshold, a comparative effect estimate, a confidence interval, or a statistical test. It also does not report how baseline pain was used in defining improvement, or how the two pain locations were handled in the analysis. Consequently, the endpoint’s definition can be described, but its comparative result cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study as completed and describes its planned primary outcome, but it does not report a primary outcome analysis. In particular, it provides no arm-specific proportions meeting the >50% improvement threshold, no estimated difference between treatment approaches, and no uncertainty interval or test result. There is therefore no registry-reported estimate from which to describe the direction, magnitude, or precision of a comparative effect.
The primary endpoint addresses categorical improvement in back pain and leg pain separately at 3 months. Even when such proportions are available, a comparison needs to be read with its uncertainty: a point estimate describes the observed contrast, while a confidence interval describes the range of values compatible with the data under the analysis assumptions. A wide interval generally indicates less precision than a narrow interval. These are general statistical principles; the registry record does not provide estimates or confidence intervals for this endpoint.
The record lists six outcome measures and names several types of pain and function measures. These include mean change in Numeric Pain Rating Scale scores, Oswestry Disability Index outcomes, and Swiss Spinal Stenosis Questionnaire outcomes. Multiple outcomes or multiple related comparisons raise questions about how the analysis distinguishes primary from secondary evidence and how it handles the chance of findings arising from repeated testing. The registry record does not report an analysis plan or results with which to assess those issues.
Adverse-event data are reported separately from efficacy results. The recorded safety figures include serious adverse events, other adverse events, and deaths for each injection group. Those counts describe reported events in the stated at-risk groups; they do not supply an estimate of pain improvement or establish a comparative treatment effect. Event counts also require context, including event definitions, timing, severity, and participant-level attribution, some of which is not reported in the registry record.
Enrollment, design, and completion status are not substitutes for outcome results. The 58-participant enrollment and crossover design give context for the trial, but do not indicate whether a result was statistically significant or clinically important. No claim that either treatment approach performed better can be drawn from the posted results described in the registry record. The appropriate interpretation is that the registry gives the study question and selected safety counts, while the comparative primary outcome result is not reported in the registry record.
9. Statistical Methods Explained
Statistical methods help connect a research question to a comparison that can be interpreted. For this study, the central outcome is categorical: whether participants reported >50% improvement in pain at 3 months. Back and leg pain are separate outcome components. The registry record specifies this endpoint and says categorical measures were selected for the primary analysis, but it does not report the detailed statistical plan or an analysis result. The explanations below describe general concepts rather than methods confirmed to have been used in this trial.
What does a categorical endpoint estimate?
A categorical endpoint places each participant into a defined outcome group, such as meeting or not meeting the stated improvement threshold. The proportion meeting the criterion can then be compared between treatment groups. A difference in proportions, if reported, would describe the observed contrast on that endpoint. It would not by itself explain how much pain changed for each participant or whether changes below the threshold were small or large. Because the registry record does not report the category counts or a comparison estimate, neither the direction nor size of such a contrast can be described.
The primary endpoint’s threshold and assessment time are specified as >50% improvement and 3 months. The record does not explain the score calculation used to establish improvement, how missing pain assessments were treated, or whether the analysis adjusted for baseline measurements. Those details matter because outcome definitions and analysis choices determine what a reported estimate represents.
How should uncertainty be read?
A confidence interval is a general way to express uncertainty around an estimated effect. It gives a range of values that are reasonably compatible with the observed data and the model assumptions. A narrower interval indicates greater precision than a wider interval, though precision alone does not establish clinical importance. The registry record does not report a confidence interval for the primary endpoint, so the precision of any treatment comparison cannot be assessed from this record.
A p-value, when reported, evaluates how compatible the observed data are with a specified null hypothesis under the statistical model. It is not the probability that the null hypothesis is true, nor does it describe the size or practical importance of an effect. No primary-outcome p-value is reported in the registry record. Statistical significance, if it had been reported, would not on its own establish the magnitude, precision, or clinical meaning of the comparison.
Why does the crossover design matter?
In a crossover design, participants receive interventions in a sequence, allowing comparisons that may use information from the same participant under different treatment conditions. This can make within-person differences relevant to the analysis. However, interpretation depends on the sequence, timing, outcome collection, and assumptions about whether an earlier treatment can affect later observations. The record identifies a crossover model but does not report treatment sequences, washout arrangements, or a statistical model accounting for repeated observations. It is therefore not possible to determine how the crossover structure was handled analytically.
Randomization is intended to reduce systematic differences in treatment assignment, while masking can reduce the influence of expectations on care or outcome assessment. These are general purposes of those design features. The record labels the study randomized and triple-masked, but does not report the allocation procedure, the people masked, or implementation details. The labels alone do not show how effectively randomization or masking was carried out.
What do the planning illustrations mean?
The sample-size illustrations use the observed effect as a planning reference, with a stated fraction of that effect as the effect to detect. Their assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For time-to-event calculations, the illustrations give the total number of events using the Schoenfeld method; other calculations give participants per arm. These are planning illustrations, not observed power and not evidence that the study was designed with those assumptions. The registry record does not report the trial’s own sample-size justification, and no calculated illustration values are specified in the registry record.
In general, power planning asks how much information a proposed study would need to detect a chosen effect under stated assumptions. It is not a measure of whether an observed result is reliable, and a post hoc calculation based on an observed effect should not be treated as confirmation of that effect. The listed assumptions are useful for understanding the illustrations, but they do not establish the assumptions used by the investigators when planning this trial.
Why can over-dispersion matter?
For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means the observed variability is greater than that model assumes. If ignored, uncertainty estimates can be too small and statistical evidence can appear stronger than warranted. This is a general consideration for count data; the primary endpoint in this study is categorical, and the registry record does not report a count-outcome model or an assessment of over-dispersion.
Overall, the available record supports a description of the endpoint, design labels, and planning assumptions, but not a reconstruction of the trial’s analysis. The statistical model, handling of crossover observations, missing-data approach, and primary comparison are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, time points, or comparisons are tested. As the number of statistical tests grows, the chance of at least one apparently notable result can increase if no adjustment or hierarchy is used. A prespecified primary outcome can help distinguish the principal question from secondary and exploratory questions, but the record’s designation of a primary outcome does not reveal how the investigators handled the several listed outcomes or the separate back and leg pain measures.
The registry record identifies the primary endpoint and lists secondary pain and function outcomes, but it does not report multiplicity procedures, a testing hierarchy, or a complete statistical analysis plan. It also does not report results for those outcomes. It is therefore not possible to determine whether adjustments were planned or applied, or how any secondary findings were intended to be interpreted relative to the primary outcome.
Missing data can affect a trial when outcome measurements are unavailable for some participants. Statistical approaches may make different assumptions about why measurements are missing, and those assumptions can influence estimates. The registry record does not report missing outcome counts, reasons for missingness, or methods for handling missing data. The analysis population is also not reported: the record does not say which randomized participants were included in each outcome analysis or how crossover participation was handled.
Interim analyses and stopping rules are not reported in the registry record. Their absence from the record cannot be taken to mean that they were or were not used. Without these details and the outcome analysis, it is not possible to assess whether the reported evidence accounts for multiplicity, missingness, or deviations from the planned analysis.
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 |
|---|---|---|---|
| Transforaminal Epidural Amniotic Fluid Injection | 1 | 28 | 3.6% |
| Transforaminal Epidural Dexamethasone Injection | 2 | 30 | 6.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Transforaminal Epidural Amniotic Fluid Injection | 0 of 28 |
| Transforaminal Epidural Dexamethasone Injection | 1 of 30 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Transforaminal Epidural Amniotic Fluid Injection | 16 of 28 |
| Transforaminal Epidural Dexamethasone Injection | 11 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Transforaminal Epidural Amniotic Fluid Injection | Transforaminal Epidural Dexamethasone Injection |
|---|---|---|---|
| Dehydration | Blood and lymphatic system disorders | 0 of 28 | 1 of 30 |
| Arthritis right knee reconstruction | Musculoskeletal and connective tissue disorders | 0 of 28 | 1 of 30 |
| Rupture of distal biceps tendon | Musculoskeletal and connective tissue disorders | 1 of 28 | 0 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Transforaminal Epidural Amniotic Fluid Injection | Transforaminal Epidural Dexamethasone Injection |
|---|---|---|---|
| Exacerbation of back pain | Musculoskeletal and connective tissue disorders | 7 of 28 | 9 of 30 |
| Leg weakness | Musculoskeletal and connective tissue disorders | 6 of 28 | 5 of 30 |
| Headache | Nervous system disorders | 6 of 28 | 4 of 30 |
| Exacerbation of typical leg pain | Musculoskeletal and connective tissue disorders | 0 of 28 | 10 of 30 |
| Insomnia | Nervous system disorders | 3 of 28 | 0 of 30 |
Serious events with the highest arm-level rate: rupture of distal biceps tendon (3.6%), dehydration (3.3%), arthritis right knee reconstruction (3.3%).
The registry record reports serious adverse events, other adverse events, and deaths by injection group. For transforaminal epidural amniotic fluid injection, 1 of 28 participants at risk had a serious adverse event and 16 of 28 had other adverse events; 0 deaths are listed. For transforaminal epidural dexamethasone injection, 2 of 30 participants at risk had serious adverse events and 11 of 30 had other adverse events; 1 death is listed. These are descriptive registry counts and should not be treated as a causal comparison.
The serious-event terms listed in the record are Rupture of distal biceps tendon (3.6%), Dehydration (3.3%), and Arthritis right knee reconstruction (3.3%). The record does not explain how these terms relate to the group totals, whether participants could contribute multiple events, or whether the events were judged related to an injection. The percentages should therefore be read as listed, without inferring an event rate or attribution beyond the registry’s presentation.
Safety counts do not establish that a treatment caused or prevented an event. Interpretation depends on event definitions, follow-up duration, ascertainment, and clinical context, which are not fully reported in the registry record. The listed denominators also describe the at-risk groups for these safety summaries, not necessarily the analysis populations for the primary outcome.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, triple-masked crossover study was conducted to compare epidural amniotic fluid allograft with dexamethasone for lumbosacral radicular pain due to spinal stenosis. It specifies a primary categorical pain outcome at 3 months, assessed separately for back and leg pain, and lists additional pain and function measures. It also provides selected adverse-event counts. These details make the clinical question and some aspects of the design clear.
They do not establish which treatment had better outcomes. The registry record does not report the primary outcome counts, comparative effect estimates, confidence intervals, or statistical tests. It also does not report analysis results for the listed secondary outcomes. Without those results, the magnitude and precision of any observed difference cannot be assessed, and no conclusion about comparative efficacy follows from the study design or its completed status.
The safety figures are not a substitute for an efficacy analysis. They describe reported events in the stated at-risk groups, but the record does not provide enough context to attribute those events to an intervention or to make a comprehensive safety comparison. Similarly, the study rationale’s statements about proposed biologic properties of hAF describe the motivation for investigation; they are not evidence that those properties produced a clinical benefit in this trial.
In general, a clinical trial result is interpreted by considering the endpoint definition, effect estimate, uncertainty, analysis population, and study limitations together. Here, several of those elements—including the primary comparative estimate, missing-data handling, and crossover analysis—are not reported in the registry record. The supported conclusion is limited: the record describes the question, design, outcomes, and selected safety data, while leaving the primary comparative result unreported.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it combines a categorical improvement endpoint with a crossover design. A threshold-based outcome asks how many participants reach a specified improvement criterion, rather than describing only an average score change. That may be a useful way to frame a clinical question, but it also makes the choice and application of the threshold important. Back and leg pain are treated separately, so readers need outcome-specific estimates to understand each comparison. Those estimates are not reported in the registry record.
The crossover design also makes the structure of the analysis important. General interpretation depends on how treatment sequences and repeated measurements are represented, and on whether effects from an earlier period can influence later observations. Although the registry record identifies a crossover model, it does not report the sequence, washout arrangements, or statistical handling of repeated observations. The design label alone cannot answer those analytical questions.
The record names pain and function outcomes beyond the primary endpoint, including measures of disability and spinal stenosis symptoms. Multiple endpoints create a need to distinguish confirmatory questions from other analyses and to interpret results with appropriate attention to multiplicity. The registry record does not report the analysis plan or results needed to evaluate that distinction.
Finally, planning assumptions and observed evidence serve different purposes. The described sample-size illustrations use specified assumptions and an observed-effect reference, but such illustrations are not observed power and do not replace a prespecified design justification. The registry record does not report the trial’s own sample-size justification. The combination of a clear clinical question and incomplete statistical reporting makes this record useful for identifying what should be assessed, while limiting what can be concluded about the comparison.
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.
Important design and analysis details are absent from the registry record. Although the study is labeled randomized, triple-masked, and crossover, the record does not describe the allocation process, who was masked, the treatment sequence, or washout arrangements. The intervention descriptions are truncated, limiting procedural comparison. These gaps make it difficult to assess implementation or reconstruct how the crossover design informed the analysis.
The primary outcome is stated as the percentage reporting >50% improvement at 3 months, with back and leg pain separate. The record does not report the outcome counts or estimates, the statistical test, confidence intervals, or analysis population. Nor does it explain the score calculation or handling of missing pain assessments. Without these details, neither the primary treatment contrast nor its precision can be evaluated.
The record lists secondary outcomes and selected adverse-event summaries, but does not report analyses for the secondary outcomes or details needed to interpret the serious-event terms. Event timing, adjudication, attribution, and participant-level overlap are not reported in the registry record. The record also does not report a complete statistical analysis plan, multiplicity procedures, interim analyses, or the trial’s sample-size justification.
These limitations concern what can be concluded from the registry record; they do not establish that a particular method was or was not used. The trial is marked completed, but completion does not fill the gaps in posted outcome reporting. The main limitation for interpreting efficacy is that the primary comparative result is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sterile Amniotic Fluid Filtrate Epidural Injection. — NCT04537026.
- Registry record last updated 2026-09-25; status last verified 2026-05.
- Results first posted 2026-09-25.
- 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
The registry record describes a completed Phase I/II randomized, triple-masked crossover study sponsored by University of Utah, with enrollment of 58. It compares transforaminal epidural amniotic fluid injection with transforaminal epidural dexamethasone injection for lumbosacral radicular pain due to spinal stenosis. The primary endpoint is the percentage reporting >50% improvement in Numeric Rating Scale pain score at 3 months, with back and leg pain assessed separately.
Listed secondary outcomes cover pain, disability, and Swiss Spinal Stenosis Questionnaire measures. The record includes safety counts for each injection group but does not report the primary outcome analysis, comparative estimates, confidence intervals, or statistical tests. Details of the crossover analysis, missing-data methods, multiplicity handling, and the trial’s sample-size justification are not reported in the registry record.