Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett's Esophagus With Radiofrequency Ablation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett's Esophagus With Radiofrequency Ablation (NCT02162758), a randomized phase 2 study. The primary outcome is Percentage of Participants With Recurrence of Intestinal Metaplasia (IM).

2. Clinical Question

The study was designed to examine recurrence after participants had achieved complete eradication with radiofrequency ablation. The endpoint therefore concerns a post-ablation biopsy finding, not initial eradication or a broader measure of Barrett's esophagus. The registry lists 6 enrolled participants, while the primary-endpoint group sizes with available Month 12 biopsy assessments are 3 for once-daily dosing and 2 for twice-daily dosing. Those endpoint denominators matter when interpreting the percentages: the posted values describe the participants with an available assessment, not a fully observed comparison across everyone enrolled.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group study sponsored by Takeda. Its masking field says quadruple masking. The record's phase field lists PHASE2, while the official title calls the study Phase 4; that inconsistency is present in the registry record and is not resolved there. The record lists Barrett's esophagus as the condition and describes the target population as participants with high-grade dysplasia who achieved complete eradication following radiofrequency ablation.

The two listed regimens were dexlansoprazole 60 mg once daily and dexlansoprazole 60 mg twice daily. The once-daily arm also received a placebo-matching capsule once daily; both descriptions specify treatment for up to 12 months. The primary endpoint was assessed at Month 12. The registry lists a start of 2014-07 and primary completion of 2016-04, and gives the study status as terminated.

Enrollment was 6. For the primary endpoint, the reported group sizes were 3 in the once-daily arm and 2 in the twice-daily arm, reflecting the stated endpoint population with a Month 12 biopsy available. These figures should not be treated as an inferentially adequate comparison by themselves; the record provides no comparative analysis. It also does not report why the study was terminated, the intended enrollment target, or details of the randomization sequence or concealment procedures. Those elements are not reported in the registry record.

Randomization is generally used to reduce systematic differences between treatment groups at assignment, while masking is generally intended to limit bias in care, assessment, or reporting. These are general design principles, not evidence that the groups in this study were balanced or that masking was maintained. With the endpoint group sizes and absence of a posted analysis, the registry results describe observed outcomes rather than establishing a precise comparative effect.

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: Participants with a diagnosis of Barrett's esophagus (BE) who had achieved complete eradication of intestinal metaplasia (CEIM) with radiofrequency ablation (RFA) were enrolled in 1 of the 2 treatment groups: Dexlansoprazole 60 milligram (mg), once-daily (QD); Dexlansoprazole 60 mg, twice daily (BID).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent-to-treat (ITT) population where Month 12 esophageal biopsy assessment was available. The ITT population included all randomized participants who had documented CEIM at screening and took at least 1 dose of study drug during the treatment period.

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: The safety set included all participants who were randomized and received 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Recurrence of Intestinal Metaplasia (IM), measured over Month 12.

The primary endpoint is the percentage of participants with recurrence of intestinal metaplasia at Month 12. The registry defines recurrence as an esophageal biopsy result indicating Barrett's esophagus, with or without dysplasia. The endpoint is binary at the participant level: each assessed participant is classified according to whether recurrence was recorded, and the reported percentage represents the proportion with that finding in the relevant group.

A biopsy-defined endpoint provides a specified way to identify recurrence after radiofrequency ablation. It also distinguishes recurrence with dysplasia from recurrence without dysplasia in the definition, while counting either finding as recurrence for the primary endpoint. The registry separately lists recurrence of intestinal metaplasia with dysplasia as a secondary outcome. That secondary outcome is not interchangeable with the broader primary definition.

The primary endpoint applies to the intent-to-treat population with a Month 12 biopsy assessment available. The record defines that population as randomized participants with documented complete eradication at screening who took at least 1 dose of study drug. The reported group sizes are 3 for once-daily dosing and 2 for twice-daily dosing. The observed percentages are 0.0% and 50.0%, respectively. Because no comparative analysis is reported, these percentages alone do not quantify the uncertainty around the difference between dosing schedules or establish a causal conclusion.

In general, a prespecified clinical endpoint helps focus interpretation on an outcome relevant to the study question. Here, the operational definition is the biopsy finding, and the assessment time is Month 12. Whether participants without an available biopsy were handled through imputation or another missing-data procedure is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage measure?

For a binary outcome such as recurrence recorded or not recorded, a percentage expresses the share of assessed participants classified as having the event. The primary endpoint uses biopsy-defined recurrence at Month 12. The posted percentages are 0.0% for dexlansoprazole 60 mg once daily and 50.0% for dexlansoprazole 60 mg twice daily. Their group sizes are 3 and 2. These values describe the observed data in the endpoint population; they do not, by themselves, describe how much uncertainty surrounds the underlying event rates.

As a general statistical principle, percentages based on small groups can change markedly when an individual outcome changes. A percentage should therefore be read together with its denominator and with an uncertainty estimate when one is available. No confidence interval is reported for this primary endpoint in the registry record.

What would a comparative analysis add?

A comparative analysis would formally estimate or test the difference between the dosing groups, using a defined statistical method and assumptions. For a binary endpoint, possible approaches in general include methods based on proportions or models for binary outcomes. The registry does not identify a method used for a primary comparison, and it reports no analysis for this endpoint. The record explicitly notes that values are missing or not estimable for a two-arm comparison of this binary percentage outcome. Therefore, no test statistic, p-value, adjusted effect estimate, or interval estimate should be inferred from the descriptive percentages.

A confidence interval is, in general, a range calculated using a statistical procedure to express the uncertainty around an estimate. It is not a guarantee that the true value lies in the displayed range. With sparse binary data, an interval can be wide, and the method used to construct it matters. Since the registry reports no interval, the precision of the group percentages cannot be quantified from the posted primary results.

How do randomization and masking relate to interpretation?

Randomization is generally intended to make treatment assignment independent of measured and unmeasured participant characteristics, on average across repeated assignments. Masking is generally intended to reduce the influence of knowledge of treatment assignment on behavior, care, outcome assessment, or reporting. The registry describes the study as randomized, double-blind, and quadruple-masked. These labels identify the design as recorded, but the registry record does not provide procedural details or evidence about whether masking was maintained. Nor can randomization ensure balance in a study with very limited enrollment.

What do the planning assumptions describe?

The record characterizes its sample-size assumptions as a planning illustration computed from the observed effect, rather than the trial's own design. It describes a two-sided significance level of 0.05, equal allocation between the arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Those assumptions are planning conventions, not observed results and not evidence of observed power. The actual trial design rationale, sample-size justification, and any target effect used by the investigators are not reported in the registry record. Planning illustrations should not be confused with the number of participants enrolled or with a claim that the trial had a particular probability of detecting an effect.

In general, over-dispersion refers to variability greater than a model assumes. It can matter when the data structure or outcome-generating process creates more variability than a simple model allows. The registry does not report an over-dispersion assessment or a model for the primary endpoint, so there is no basis for claiming that such an adjustment was used or needed in this analysis. The main interpretive issue visible in the posted results is the sparse endpoint information and the absence of a comparative analysis.

What is and is not posted?

The primary outcome is a percentage of participants with an event, and its dispersion field is not populated. No primary analysis is listed; the registry reports 0 analyses. The record lists 4 outcome measures and 3 secondary outcomes, but a listing of outcomes does not mean results or analyses are available for each. No interim analyses, statistical analysis plan, or multiplicity procedure is reported in the registry record. These omissions do not establish what investigators did outside the record; they limit what can be concluded from the posted statistical information.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Dexlansoprazole 60 mg QD", "Dexlansoprazole 60 mg BID")
n      <- c(3, 2)
events <- c(0, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Dexlansoprazole 60 mg QD  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Dexlansoprazole 60 mg BID  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures: the primary recurrence endpoint and 3 secondary outcomes. Those secondary outcomes are recurrence of intestinal metaplasia with dysplasia, erosive esophagitis, and change from baseline in the Gastroesophageal Reflux Disease-Health Related Quality of Life total score. The record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or another procedure to control the chance of false-positive findings across multiple tests. It also reports 0 analyses, so no inferential outcome results are available to interpret across this set.

The primary endpoint population includes participants with a Month 12 biopsy assessment available, in addition to the stated randomization, screening, and treatment-dose criteria. The registry gives endpoint group sizes of 3 and 2. It does not state how many participants lacked a Month 12 biopsy, why any assessment was unavailable, or whether missing outcomes were imputed. No missing-data sensitivity analysis is reported. These details are not reported in the registry record.

In general, missing outcome data can affect both the estimated event proportion and the comparability of treatment groups if availability is related to participant characteristics or outcomes. The direction and size of any such effect cannot be determined from the information recorded. The registry's definition of the endpoint population makes clear that the posted percentages are based on available Month 12 biopsy assessments; they should not be assumed to represent outcomes for participants without an assessment.

The record also does not report an interim-analysis plan, stopping rules, or a statistical analysis plan. The study status is terminated, but the reason and its relation, if any, to the reported outcome data are not reported in the registry record. No explanation should be inferred from termination status alone.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypotension (33.3%), aspiration pneumonia (33.3%), worsening of back pain (33.3%).

The registry reports serious adverse event data for both dosing groups, with 3 participants at risk in each group. It lists 1 participant affected by a serious adverse event in the once-daily group and 2 in the twice-daily group. For other adverse events, it lists 3 participants at risk in each group, with 2 affected in each group. These are separate registry fields for serious and other adverse events; they should not be added together or treated as mutually exclusive participant counts.

The record lists Hypotension, Aspiration pneumonia, and Worsening of back pain among the top serious adverse event terms, each with a reported percentage of 33.3%. It does not identify the treatment group associated with each term in the listed information, so a group-specific interpretation is not supported. The deaths field is null for both groups; deaths are not reported in the registry record.

These figures are safety descriptions, not a formal comparison of risks. The registry does not provide a comparative analysis, uncertainty estimates, or enough contextual detail to establish whether the observed counts differ beyond chance. In general, adverse-event counts need interpretation alongside exposure, event definitions, timing, severity, and participant-level context. Those details are not reported in the registry record. The values therefore describe the posted event counts and terms only; they do not establish a treatment effect or provide a basis for medical advice.

13. What the Result Does, and Does Not, Mean

The record documents a randomized, masked comparison of dexlansoprazole 60 mg once daily and 60 mg twice daily in participants who had achieved complete eradication of Barrett's esophagus with high-grade dysplasia after radiofrequency ablation. Its primary endpoint was biopsy-defined recurrence of intestinal metaplasia at Month 12. The posted percentages were 0.0% for once-daily dosing and 50.0% for twice-daily dosing, based on endpoint group sizes of 3 and 2.

These observations show what was recorded among participants with an available Month 12 biopsy in the defined endpoint population. They do not establish that the regimens differ in their effects on recurrence. The registry provides no comparative estimate, confidence interval, p-value, or other primary-endpoint analysis, and indicates that values for a two-arm comparison were missing or not estimable. The observed percentages should therefore not be presented as a confirmed effect or as evidence that one regimen is better or worse.

The results also do not describe outcomes for every enrolled participant without qualification. The endpoint population required a Month 12 biopsy assessment, and the registry does not report the handling of missing assessments. Nor do the primary results answer the listed secondary questions about recurrence with dysplasia, erosive esophagitis, or quality of life.

In general, a clinical trial's observed data, statistical uncertainty, and causal interpretation are related but distinct. Randomization and masking are features of the design; they do not replace a reported analysis or resolve uncertainty created by limited outcome information. The status of terminated, the registry's phase discrepancy, and the absence of statistical details further constrain interpretation. The reason for termination and the study's original statistical plan are not reported in the registry record.

The defensible conclusion is descriptive: the record contains the stated biopsy percentages and adverse-event counts for this small terminated study, but it does not supply a comparative statistical result sufficient to establish the effect of dosing frequency on recurrence.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a visible difference in observed percentages and a supported estimate of a treatment contrast. The primary endpoint values are 0.0% and 50.0%, but the group sizes with an available biopsy are 3 and 2, and the registry reports no comparative analysis. A striking-looking percentage contrast can coexist with substantial uncertainty when the underlying groups are sparse. Without an inferential estimate or interval, readers cannot judge the precision of the contrast from the registry results.

The record also illustrates why the analysis population matters. The primary endpoint applies to participants meeting the stated eligibility and treatment criteria who had a Month 12 biopsy available. That is a narrower description than simply referring to enrollment. The registry does not explain missing assessments or their treatment, so the observed data cannot be assumed to represent every enrolled participant.

Another statistical issue is the difference between a trial's original design and retrospective planning calculations. The registry describes sample-size assumptions as an illustration based on the observed effect, not as the trial's own design. Such calculations are not observed power and cannot repair the absence of a reported comparative analysis. The record does not report the original sample-size justification or statistical plan.

Finally, the record's phase designation differs between its phase field and official title, and the status is terminated without an explanation. These registry entries do not themselves determine the validity of the outcome data, but they are important context when assessing completeness and reproducibility. The case demonstrates why design labels, endpoint definitions, analysis populations, missing-data handling, and uncertainty estimates all matter alongside point percentages.

15. 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 primary endpoint rests on a limited amount of available information: the registry reports group sizes of 3 and 2 for Month 12 biopsy assessment. It provides percentages but no confidence intervals or comparative test, and it states that values are missing or not estimable for a two-arm comparison. The precision of the observed rates is therefore not quantified in the record.

The endpoint population excludes anyone who did not meet the stated criteria, including the requirement for an available Month 12 biopsy. The registry does not report the number or characteristics of participants without an assessment, the reasons assessments were missing, or how missing outcomes were handled. It is not possible to assess potential bias from missing data using the posted information.

The record lists secondary outcomes but does not provide their results or analyses. It does not report a multiplicity strategy, a statistical analysis plan, interim analyses, the randomization procedure, or the reason for termination. The phase field says PHASE2, whereas the official title describes a Phase 4 study. The registry record does not reconcile these details.

The adverse-event information gives counts and selected serious-event terms but does not provide a comparative safety analysis, uncertainty estimates, or group attribution for the listed top terms. Deaths are not reported in the registry record. These limitations restrict interpretation to the descriptive details recorded; they do not establish what additional information may exist outside the registry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett's Esophagus With Radiofrequency Ablation — NCT02162758.
• Registry record last updated 2017-05-11; status last verified 2017-03.
• Results first posted 2017-05-11.
• 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.

19. Record Summary

The registry record describes a randomized, double-blind, quadruple-masked, parallel-group study of dexlansoprazole 60 mg once daily versus 60 mg twice daily after complete eradication of Barrett's esophagus with high-grade dysplasia by radiofrequency ablation. The once-daily group also received matching placebo capsules. The record lists 6 enrolled participants, a study start of 2014-07, primary completion of 2016-04, and status terminated.

The primary endpoint was biopsy-defined recurrence of intestinal metaplasia at Month 12. The posted percentages were 0.0% for once-daily dosing and 50.0% for twice-daily dosing, with endpoint group sizes of 3 and 2. The registry reports no comparative analysis and no inferential estimate. It lists 3 secondary outcomes, but no results for them are included in the record details. The phase field and official title use different phase descriptions, and the reason for termination is not reported in the registry record.