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 Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation (NCT02521285), a randomized phase 2 study. The primary outcome is Difference in the Change of CDX2 mRNA Levels in Esophageal Mucosa Between Participants Taking Aspirin and Placebo at 12 Months (Location A).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02521285 |
| Phase | Phase 2 |
| Condition | Barrett Esophagus, Esophageal Adenocarcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with Barrett esophagus after successful elimination by radiofrequency ablation. The registry record reports enrollment of 21 participants and describes withdrawals and other losses in the primary outcome population.
Intervention
Aspirin taken by mouth once daily for 12 months.
Comparator
Placebo taken by mouth once daily for 12 months.
Primary question
At 12 months, does the change in CDX2 mRNA levels in esophageal mucosa at Location A differ between participants assigned aspirin and those assigned placebo?
The registry describes a randomized, double-masked, parallel phase II trial. Its focus is a tissue biomarker after radiofrequency ablation, rather than a reported comparison of clinical recurrence. The primary measure concerns the change in the percentage of CDX2 mRNA levels from baseline to 12 months at Location A, described as 1 cm above the gastroesophageal junction. The trial also includes outcomes related to adverse events and additional tissue biomarkers.
The clinical context in the registry is prevention of Barrett esophagus returning after it has been eliminated by ablation. The brief summary describes CDX2 as a specific protein linked to developing Barrett esophagus and says tissue samples are studied to help assess whether aspirin can prevent recurrence. The primary endpoint, however, is a biomarker measure. Whether that measure corresponds to a difference in clinical recurrence is not reported in the registry record.
3. Trial Design
The registry record identifies NCT02521285 as a randomized, double-masked, parallel phase II trial sponsored by the National Cancer Institute. It reports enrollment of 21 participants. The study began on 2016-01-15, and its primary completion date is listed as 2019-06-18. Its status is active, not recruiting. That status and the listed completion date do not, by themselves, establish that all analyses or follow-up are complete.
Participants were assigned to one of two arms. Arm A received aspirin by mouth once daily for 12 months, and Arm B received placebo by mouth once daily for 12 months. The aspirin dose is not reported in the registry record. Double masking means that the record describes the trial as masked, but which study roles were masked is not reported in the registry record. The method used to generate the random assignment and the allocation concealment procedures are not reported in the registry record.
The primary outcome uses tissue measurements at baseline and 12 months. Its specified location is Location A, described as 1 cm above the gastroesophageal junction. Other registered outcomes include CDX2 mRNA at additional locations and time points, NF-kB activation measures, thromboxane B2 at 12 months, and adverse events. The registry lists 31 outcome measures and 35 analyses. The primary outcome is not reduced to one comparison in the posted results because it has several categories or time points.
The full protocol, the planned statistical analysis, the original sample-size justification, and details of interim analyses are not reported in the registry record. No dosage amount, adherence results, or arm-specific account of treatment exposure is reported in the registry record.
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: 21 participants were randomized due to 12 were unevaluable.
Overall Study
| Stage | Arm A (Aspirin) | Arm B (Placebo) |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Arm A (Aspirin) | Arm B (Placebo) |
|---|---|---|
| Lost to Follow-up | 1 | 1 |
| Withdrawal by Subject | 1 | 1 |
| Adverse Event | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: 1 participant withdrew consent and decided to take a baby aspirin, per PCP recommendation in the Aspirin arm and 1 participant was lost to follow up, 1 participant withdrew consent, and 1 participant adverse event in the Placebo arm
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.
Population: All randomized participants.
| Characteristic | Unit | Arm A (Aspirin) | Arm B (Placebo) | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 11 | 21 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 | 3 | 8 |
| Age, Categorical: >=65 years | Participants | 5 | 8 | 13 |
| Age, Continuous | years | 64.5 (49 to 78) | 67 (49 to 84) | 67 (49 to 84) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 7 | 8 | 15 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 9 | 11 | 20 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Region of Enrollment: United States | participants | 10 | 11 | 21 |
| Baseline cdx2/normalized to GAPDH | percentage of biomarker levels | 0.34 (0.005 to 0.908) | 0.438 (0.064 to 4.537) | 0.384 (0.005 to 4.537) |
| Baseline p-p65/total p65 corrected for tubulin | percentage of biomarker levels | 0.484 (0.046 to 0.838) | 0.624 (0.108 to 1.916) | 0.484 (0.046 to 1.916) |
6. Primary Endpoint
The registry lists the primary outcome as Difference in the Change of CDX2 mRNA Levels in Esophageal Mucosa Between Participants Taking Aspirin and Placebo at 12 Months (Location A), measured over Baseline and 12 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | change of percentage of CDX2 mRNA levels |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the difference between the aspirin and placebo groups in change in CDX2 mRNA levels in esophageal mucosa at 12 months, at Location A. The registered unit is change in the percentage of CDX2 mRNA levels. Measurements are specified at baseline and 12 months, and the endpoint uses the median with the full range as its dispersion summary. Location A is described as 1 cm above the gastroesophageal junction.
The registry says the assay assessed absolute and relative percentage values for the biomarker in esophageal mucosa. Total RNA was isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantified by spectrophotometry. The measure is a molecular biomarker, not a direct count of Barrett esophagus recurrence or esophageal cancer cases.
In general, a biomarker endpoint can offer a biological measure that may help researchers study processes related to disease. The registry’s summary describes CDX2 as linked to developing Barrett esophagus. That rationale does not establish that a measured change predicts, prevents, or is equivalent to a clinical outcome. The primary endpoint results, including group medians and full ranges, are not reported in the registry record. It is therefore not possible to describe the direction, size, or precision of a between-group difference from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a biomarker comparison but does not report its numerical results. There are no posted aspirin or placebo medians, full ranges, estimated between-group difference, confidence interval, or p-value for the primary endpoint. The record therefore does not establish whether the observed CDX2 mRNA changes differed between groups, how large any difference was, or how precisely it was estimated. A direction or magnitude should not be inferred from the study question or the trial’s rationale.
The endpoint is a change in a tissue biomarker, measured from baseline to 12 months. It should not be described as a direct estimate of recurrence prevention. The registry’s brief summary frames the study as examining whether aspirin may prevent Barrett esophagus from returning, but the primary endpoint reported is CDX2 mRNA. Clinical recurrence results are not reported in the registry record. A biomarker change could be relevant to biological understanding without, on its own, demonstrating a change in a clinical outcome.
The total enrollment is 21, and the primary outcome population description records withdrawals and loss to follow-up in both arms. The small enrollment and the reported outcome-population issues are important context for interpreting any estimates if results become available. With limited participant information, an estimate can be imprecise; a confidence interval, when reported, would convey the range of values compatible with the data under the analysis assumptions. No such interval for the primary endpoint is reported in the registry record.
The posted safety figures report serious adverse events in 3 of 8 participants at risk in the aspirin arm and 2 of 8 in the placebo arm. Other adverse events are reported for 7 of 8 and 8 of 8 participants at risk, respectively, and no deaths are reported in either group. These are descriptive counts in small groups, not a complete comparative safety analysis. Event severity, timing, relatedness, and the statistical uncertainty around group differences are not reported in the registry record.
Any sample-size values presented as planning illustrations should be read as hypothetical calculations based on an observed effect and stated assumptions, not as observed power or as the trial’s original design justification. The registry record does not report the original sample-size justification or a complete analysis plan. In the absence of outcome estimates and analysis details, the posted record supports description of the design and registered measurements, but not a conclusion about efficacy or the size of a biomarker effect.
9. Statistical Methods Explained
The trial is registered as randomized, double-masked, and parallel. In general, randomization is intended to reduce systematic differences between assigned groups, while masking can reduce the influence of expectations on care, measurement, or reporting. The registry does not report the randomization procedure, which study roles were masked, or the procedures used to preserve masking. A parallel design means the listed arms are distinct groups assigned to aspirin or placebo; the registry does not describe a crossover between treatments.
What does the median and full range describe?
The primary endpoint specifies a median and full range for the change in CDX2 mRNA levels. In general, the median is the middle value when observations are ordered and can describe a typical observation without relying on the arithmetic mean. The full range reports the lowest and highest observed values, and therefore shows the total spread but can be sensitive to extreme observations. These summaries do not, by themselves, quantify the uncertainty in a difference between groups. The primary outcome values and an inferential comparison are not reported in the registry record.
What is meant by change from baseline?
The registered measure compares biomarker levels at baseline with levels at 12 months. In general, a change score is derived from observations at two time points for the same participant. A between-group comparison of change asks whether the distribution of those changes differs between assigned groups. The registry describes the endpoint as the difference in the change, but does not report the actual group summaries or the statistical procedure used to make that comparison. It is not reported whether the analysis used a particular transformation, covariate adjustment, or model.
What does the assay measure?
The endpoint concerns CDX2 mRNA in esophageal mucosa, not the amount of a circulating substance or a clinical diagnosis. The registry describes measurements of absolute and relative percentage values at baseline and 12 months. It says total RNA was isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantified by spectrophotometry. Location A is specified as 1 cm above the gastroesophageal junction. Details such as laboratory quality-control procedures, repeatability, handling of values outside assay limits, and whether laboratory personnel were masked are not reported in the registry record.
How should other statistical displays be understood?
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis; it does not represent the range of individual participant outcomes. A p-value measures how compatible the observed data are with a specified null model, rather than the probability that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record. No statistical model or testing procedure for the primary endpoint is reported.
Planning illustrations, if used, are not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event calculations, the stated output is total events using the Schoenfeld method; for other calculations, it is participants per arm for 80% power or another stated power level. These are planning calculations, not evidence that the trial had a particular probability of detecting an effect. The original design assumptions and sample-size justification are not reported in the registry record.
Why can variability matter?
In general, greater variability in measurements makes it harder to distinguish a group difference from random variation. Biomarker measurements may vary across participants and tissue locations. The registry lists outcomes at several locations for some biomarkers, but does not report the variability estimates, correlations among measurements, or a method for accounting for such structure. If data are over-dispersed relative to a model’s assumptions, conventional standard errors can be too small; methods that account for extra variability may be needed. This is a general statistical consideration, not a claim that over-dispersion occurred in this trial.
The record reports 31 outcome measures and 35 analyses. That breadth matters when many outcomes or comparisons are examined, but the statistical methods used to handle multiple testing are not reported in the registry record. The primary results themselves are also not reported, so there is no basis for reconstructing estimates or testing results from the registry description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 31 outcome measures and 35 analyses. The primary outcome is described as having several categories or time points and is not reduced to one comparison in the posted results. Additional registered outcomes include adverse events, CDX2 mRNA changes at 18 months for Locations A, B, and C, NF-kB activation measures at those locations and time point, and a change in thromboxane B2 at 12 months for Location A. The full list includes other registered measures, but the multiplicity strategy is not reported in the registry record.
In general, testing many outcomes or comparisons can increase the chance that at least one result appears unusual by chance. Statistical approaches can address this issue by defining a primary comparison in advance or adjusting inference across tests. Whether the trial prespecified a hierarchy, used an adjustment, or treated secondary outcomes as exploratory is not reported in the registry record. The registry record does not report a full statistical analysis plan, interim analyses, or rules for selecting analyses for presentation.
For the primary outcome population, the record describes one participant in the aspirin arm who withdrew consent and decided to take baby aspirin per a primary care provider’s recommendation. In the placebo arm, it describes one participant lost to follow-up, one withdrawal of consent, and one adverse event. The analysis population definitions, missing-data methods, and handling of these participants in each analysis are not reported in the registry record.
In general, missing observations can affect estimates if the likelihood of missingness is related to participants’ outcomes or treatment experience. Different methods can rely on different assumptions about missing data. The registry does not report whether analyses followed intention-to-treat principles, used available cases, imputed missing values, or applied another approach. It is therefore not possible to assess how missing outcome data may have influenced the primary comparison from the posted record.
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 |
|---|---|---|---|
| Arm A (Aspirin) | 3 | 8 | 37.5% |
| Arm B (Placebo) | 2 | 8 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A (Aspirin) | 0 of 8 |
| Arm B (Placebo) | 0 of 8 |
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 |
|---|---|
| Arm A (Aspirin) | 7 of 8 |
| Arm B (Placebo) | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A (Aspirin) | Arm B (Placebo) |
|---|---|---|---|
| Subdural Hematoma | Vascular disorders | 0 of 8 | 1 of 8 |
| Drainage of Subdural Hematoma | Surgical and medical procedures | 0 of 8 | 1 of 8 |
| Parotidectomy | Surgical and medical procedures | 1 of 8 | 0 of 8 |
| Small Bowel Obstruction | Gastrointestinal disorders | 1 of 8 | 0 of 8 |
| Severe Stenosis | Musculoskeletal and connective tissue disorders | 0 of 8 | 1 of 8 |
| Hiatus Hernia Repair | Surgical and medical procedures | 1 of 8 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A (Aspirin) | Arm B (Placebo) |
|---|---|---|---|
| Cough/Cough due to Cold Symptoms | Respiratory, thoracic and mediastinal disorders | 2 of 8 | 1 of 8 |
| Headache | Nervous system disorders | 3 of 8 | 0 of 8 |
| Flu like symptoms(Sick/Cough due to cold symptoms/Nasal and chest congestion) | General disorders | 2 of 8 | 1 of 8 |
| Nausea/Nausea and Vomiting | Gastrointestinal disorders | 3 of 8 | 0 of 8 |
| Abdominal pain/Abdominal pain with Bloating | Gastrointestinal disorders | 2 of 8 | 0 of 8 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 8 | 2 of 8 |
| Constipation | Gastrointestinal disorders | 1 of 8 | 1 of 8 |
| Edema-Limbs | General disorders | 1 of 8 | 1 of 8 |
| Acid Reflux | Gastrointestinal disorders | 1 of 8 | 0 of 8 |
| Arthritis | Musculoskeletal and connective tissue disorders | 1 of 8 | 0 of 8 |
Serious events with the highest arm-level rate: subdural hematoma (12.5%), drainage of subdural hematoma (12.5%), parotidectomy (12.5%), small bowel obstruction (12.5%), severe stenosis (12.5%).
The registry reports serious adverse events for 3 of 8 participants at risk in Arm A (Aspirin) and 2 of 8 participants at risk in Arm B (Placebo). Other adverse events are reported for 7 of 8 participants at risk in the aspirin arm and 8 of 8 in the placebo arm. No deaths are reported in either group. These are counts of participants affected, as presented in the registry, and should be read as descriptive safety information rather than a formal estimate of comparative risk.
The listed serious-event terms are Subdural Hematoma, Drainage of Subdural Hematoma, Parotidectomy, Small Bowel Obstruction, Severe Stenosis, and Hiatus Hernia Repair. Each is listed as 12.5%. The registry record does not provide enough detail in this summary to infer whether terms occurred in the same participant, how events were distributed over time, or whether events were considered related to study treatment. The term percentages should not be added together or interpreted as a participant-level rate.
In general, safety comparisons require context about event definitions, duration of observation, severity, and attribution, as well as uncertainty around the estimates. Such details and a formal statistical comparison are not reported in the registry record. With 8 participants at risk in each arm, the counts are limited descriptive evidence and cannot establish a precise difference between groups.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of aspirin and placebo after successful radiofrequency ablation for Barrett esophagus. It specifies a primary biomarker endpoint: the difference between groups in change in CDX2 mRNA levels in esophageal mucosa at 12 months, measured at Location A. It also registers safety and other biomarker outcomes. These design details explain what the trial set out to examine.
The record does not report the primary outcome values, a between-group estimate, its uncertainty, or a p-value. It also does not report a clinical recurrence result. Consequently, the posted information does not establish whether aspirin and placebo groups differed in CDX2 mRNA change, whether any difference was large or small, or whether Barrett esophagus recurred at different rates. It would be inappropriate to treat the study question or its biological rationale as a result.
Even if a biomarker difference were reported, interpreting it would require attention to the measurement process, outcome population, missing observations, and multiplicity across the listed outcomes. In general, a biomarker is not automatically a validated substitute for a clinical outcome. The registry does not report evidence that CDX2 mRNA change predicts or reliably represents clinical recurrence in this trial.
The safety counts describe participants with serious and other adverse events and report no deaths. They do not, by themselves, show whether an event was caused by treatment or provide a precise comparative safety estimate. The record does not report the additional context needed to make those judgments. Overall, the available registry information supports understanding the design and measurement plan, but not a conclusion that aspirin is beneficial, ineffective, or associated with a particular level of risk.
13. Why This Trial Matters Statistically
This trial is statistically notable for asking a biological question after successful radiofrequency ablation while using a biomarker as its primary endpoint. The endpoint is a change in CDX2 mRNA in esophageal mucosa, measured at baseline and 12 months. That focus can help distinguish a mechanistic or biomarker question from the clinical question of whether Barrett esophagus returns. The registry’s summary links CDX2 to developing Barrett esophagus, but does not establish that its change is a substitute for recurrence outcomes.
The study is randomized, double-masked, and parallel, which provides a framework for comparing assigned groups. At the same time, the record reports enrollment of 21 participants and several outcome measures and analyses. Those features make precision, missing-data handling, and multiplicity particularly relevant when interpreting any results. The registry does not report the primary estimate or the analysis procedures needed to assess these issues.
Statistically, the distinction between a planned question and an observed estimate is central. A protocol rationale, a list of outcomes, and sample-size planning assumptions cannot answer whether the groups differed. Likewise, a biomarker result would need its magnitude and uncertainty, plus context about the analysis population and missing data. These components are not reported for the primary comparison in the registry record.
The record also illustrates why safety counts require careful interpretation. Counts of affected participants are useful descriptive information, but limited group sizes and absent details about event timing, relatedness, and analysis constrain comparative conclusions. The trial’s design and registered measurements are informative about what was studied; the unavailable outcome results prevent a statistical assessment of the central treatment 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.
The main limitation for interpreting the trial is that the primary endpoint results are not reported in the registry record. Group medians, full ranges, between-group estimates, confidence intervals, and p-values are not available. Without these, the direction, magnitude, and precision of the biomarker comparison cannot be described.
The endpoint is a tissue biomarker rather than a direct clinical recurrence outcome. The registry’s rationale connects CDX2 to Barrett esophagus, but does not report validation of CDX2 mRNA change as a surrogate for recurrence or other clinical outcomes. Clinical recurrence results are not reported in the registry record.
Enrollment was 21, and the primary outcome population description reports withdrawals and loss to follow-up. It does not state how these participants were handled in the primary analysis. The analysis populations and missing-data methods are not reported in the registry record. Those omissions make it difficult to evaluate the effect of missing observations or whether the analysis preserved the randomized comparison.
The record lists many outcomes and analyses, including measurements at several tissue locations and time points. The plan for multiplicity control, the prespecified analysis hierarchy, and any interim analyses are not reported in the registry record. Nor are the detailed statistical model, assumptions, or original sample-size justification reported. The described sample-size planning illustrations should not be confused with the trial’s design rationale or with observed power.
The safety information is also limited to summarized participant counts and listed serious-event terms. Event timing, treatment relatedness, and formal between-group uncertainty are not reported. Finally, the registry status is active, not recruiting; the record does not establish that all study reporting or follow-up is complete.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation — NCT02521285.
- Registry record last updated 2026-09-11; status last verified 2026-09.
- Results first posted 2023-05-01.
- 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
NCT02521285 is a National Cancer Institute-sponsored randomized, double-masked, parallel phase II trial in patients with Barrett esophagus after successful radiofrequency ablation. It reports enrollment of 21 and compares aspirin taken by mouth once daily for 12 months with placebo taken by mouth once daily for 12 months. The listed status is active, not recruiting.
The primary endpoint is the difference in change in CDX2 mRNA levels in esophageal mucosa from baseline to 12 months at Location A, specified as 1 cm above the gastroesophageal junction. The endpoint is summarized as a median and full range. The registry also lists adverse events and other biomarker outcomes.
The registry record does not report the primary endpoint results, a clinical recurrence comparison, or the detailed statistical analysis plan. It reports serious adverse events in 3 of 8 participants at risk in the aspirin arm and 2 of 8 in the placebo arm, other adverse events in 7 of 8 and 8 of 8, respectively, and no deaths in either arm.