Pilot Study To Investigate The Association Between Acid Control And Heartburn Symptoms After Proton Pump Inhibitor Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study To Investigate The Association Between Acid Control And Heartburn Symptoms After Proton Pump Inhibitor Treatment (NCT02708355), a randomized phase 4 study. The primary outcome is Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn.

2. Clinical Question

The distinction between an association question and a treatment-effect question matters. The stated purpose was to investigate the association between acid suppression and symptom relief, while the randomized design assigned participants to treatment schedules or placebo. The record does not provide the analysis linking individual pH measurements to symptom reports, nor does it report the primary endpoint counts needed to examine group differences. It therefore supports describing the trial question and its measurement approach, but not drawing a conclusion about the size or direction of an association.

3. Trial Design

This was a pilot Phase IV study described as multicenter, randomized, double blind, placebo-controlled and parallel. The registry records quadruple masking, random allocation and a parallel model. Enrollment is listed as 55. The study status is completed; its recorded start is 2016-01 and its primary completion is 2016-04. These registry entries describe the design and timing but do not establish how many participants contributed to each analysis.

Three groups are described: esomeprazole 20 mg twice daily, esomeprazole 20 mg once daily plus placebo, and placebo. The schedules were oral, with morning and evening dosing. The once-daily group received placebo in the evening, while the placebo group received placebo at both times. The record lists esomeprazole 20 mg and placebo as the interventions. It does not report further details about adherence, allocation concealment, or the randomization procedure.

The clinical focus was frequent heartburn, and the study purpose was to investigate the association between gastric acid suppression and relief of 24-hour heartburn following esomeprazole treatment. The stated primary outcome uses daily symptom diaries over Day 8 up to Day 14 and identifies participants with and without relief. The measure’s definition also refers to pH monitoring at Day -1 and Day 14, and the described per-protocol population requires valid data from both monitoring periods.

A pilot designation signals that the study was framed as an exploratory investigation; it does not itself establish the precision of the findings or determine what analyses were performed. The registry record does not report the protocol’s sample-size justification, an interim-analysis plan, or detailed statistical methods. The posted primary endpoint counts and group comparisons are not reported in the registry record, so the study’s observed clinical results cannot be characterized from these details alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol analysis set included all randomized participants who provided valid data for Day -1 PH monitoring, take at least one dose of randomized study medication, complete the 14 day treatment phase, undergo and provide valid data for Day 14 pH monitoring and complete at least 5 days of diary entries in each of Days -7 to -1 and Days 8 to 14.

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: Safety population included all participants who received at least 1 dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn, measured over Day 8 up to Day 14.

The primary endpoint counts participants with relief of 24-hour heartburn and participants without relief. It is assessed over Day 8 up to Day 14. The diary question asked about the severity of the most intense heartburn episode over the preceding 24 hours, including the previous day and night. Responses used a scale from 0 to 2, where 0 meant complete relief and 2 meant maximum severity; a higher score indicated worse symptoms. Relief required a daily response of 0 on at least 6 of the participant’s last 7 consecutive treatment days, allowing one day with a maximum severity of 2.

This endpoint converts repeated diary reports into a participant-level classification. In general, such a binary measure can make an outcome easier to interpret as the number of participants meeting a defined symptom criterion. It also compresses the diary information: participants with different patterns of symptom severity may fall into the same relief or no-relief category. The threshold and permitted exception are therefore important to interpreting what “relief” means in this trial.

The registry describes the endpoint and its timeframe but does not report the numbers in either category for any group. It also does not report a treatment contrast, uncertainty interval, or significance test for this outcome. The per-protocol population description links eligibility for the analysis to valid pH monitoring and diary data, but its final diary criterion is incomplete in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint count?

The registry’s primary measure is binary at the participant level: each participant is classified as having relief or not having relief according to a diary rule. The rule requires a response of 0 on at least 6 of the last 7 consecutive treatment days, with one day allowed to have a maximum severity of 2. The diary scale ranges from 0, complete relief, to 2, maximum severity, and higher values indicate worse symptoms. The outcome timeframe is Day 8 up to Day 14.

In general, a binary endpoint simplifies a repeated symptom record into categories that can be compared between groups. That simplicity comes with a trade-off: the classification does not preserve every detail of symptom timing or severity. The chosen definition determines how borderline diary patterns are categorized. For this trial, the registry states the rule, but does not report the resulting counts by group.

What can a randomized design tell readers?

Random allocation is intended, in general, to make assigned groups comparable with respect to factors that could affect outcomes, apart from chance differences. A parallel design assigns participants to a group that remains their assigned comparison group during the study. Masking is intended to reduce the influence of knowledge about assigned treatment on participant experience, care, or assessment. The registry describes this study as randomized, parallel and quadruple masked, but does not report the implementation details needed to assess those protections.

Randomization and masking do not replace outcome reporting. To interpret a group comparison, readers need the observed outcomes, the population analyzed, and the statistical approach. The primary counts and inferential comparison are not reported in the registry record. The trial’s stated aim also concerns an association between acid suppression and symptom relief; the record does not specify the statistical model or procedure used to analyze that association.

How should uncertainty be interpreted?

In general, an effect estimate describes the direction and size of a comparison, while a confidence interval conveys uncertainty around that estimate under the chosen method. A p-value addresses compatibility with a specified null hypothesis; it does not measure the probability that a treatment works, nor does it describe clinical importance. These concepts can only be applied to this trial if its endpoint data and analysis are available. The registry record does not report a confidence interval or p-value for the primary outcome.

Because the outcome is a participant count in two categories, possible analyses could compare proportions or model the binary outcome. This is general statistical context, not a description of the method used in this study. The analysis method, adjustment variables, and treatment contrast are not reported in the registry record. It would therefore be inappropriate to attach a particular estimate or test to the endpoint based only on its description.

What do the planning illustrations represent?

The planning assumptions describe illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is stated as a fraction of the observed effect. Such illustrations are prospective planning calculations: they ask how many participants per arm would be needed under specified assumptions to detect a target effect with a selected power. They are not observed power, and they are not evidence that the study was designed using those assumptions.

In general, planning calculations depend on the assumed effect, variability or event frequency, allocation, significance level, and analysis method. If the assumed effect is uncertain, the resulting sample-size illustration is uncertain as well. The registry record does not report the trial’s own sample-size justification or establish that the illustrative assumptions were part of its protocol. No particular planning value should be interpreted as the trial’s actual enrollment or analysis size.

Why can over-dispersion matter?

General statistical note: over-dispersion occurs when observed variability exceeds what a model assumes. It can make standard errors too small if the model does not account for the extra variability, which can make uncertainty appear narrower than it is. Over-dispersion is especially relevant to certain count models, but the registry describes the primary outcome as participant counts in two categories and does not report a model or an over-dispersion assessment. It should not be inferred that such a problem occurred in this trial.

The relevant statistical reading is therefore limited. The registry supplies a defined endpoint and planning assumptions, but not the primary outcome estimates, their uncertainty, or a detailed analysis plan. General statistical principles explain what those quantities would mean; they cannot substitute for the trial’s unreported results.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome with two reported categories: participants with relief and participants without relief. It does not provide the category counts by group or identify a single treatment contrast for interpretation. The record therefore does not support an assessment of how the primary outcome was tested or whether multiple comparisons were addressed.

Multiplicity arises in general when analyses test multiple outcomes, contrasts, subgroups, or time points, increasing the chance of at least one apparently notable result under a null setting. Methods such as prespecifying a primary contrast or adjusting inference can address this issue, but the registry record does not report a multiplicity strategy. The number of outcome measures and analyses listed in the record does not establish the complete set of analyses conducted or how they were handled.

The primary population is described as a per-protocol set requiring randomization, valid Day -1 pH monitoring, at least one dose of randomized study medication, completion of the 14-day treatment phase, valid Day 14 pH monitoring, and diary completion. The final diary requirement is cut off after “complete at least 5 days of diary e,” so its full wording is not reported in the registry record. The primary outcome counts for this population are not reported.

In general, missing diary or pH data can affect who qualifies for an analysis and how representative that analysis is of everyone randomized. The record does not describe imputation, missing-data sensitivity analyses, or the handling of participants excluded from the per-protocol set. Enrollment is listed as 55, but that figure does not tell readers how many participants contributed to the primary endpoint. The analysis populations and their outcome denominators are not reported in the registry record.

11. 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 non-serious adverse event terms

The registry lists serious adverse events for each study group. The number at risk is 21 for esomeprazole 20 mg twice daily, 22 for esomeprazole 20 mg once daily plus placebo, and 12 for placebo. The recorded serious adverse event count is 0 in each group. These figures describe the listed safety observations; they do not establish that no other harms occurred or that the groups were equivalent in safety.

Other adverse events are listed for 3 participants in the twice-daily group, 1 participant in the once-daily plus placebo group, and 2 participants in the placebo group. These are counts, not rates, and no statistical comparison is reported in the registry record. The adverse-event terms are not reported in the registry record. Deaths are also not reported in the registry record.

In general, adverse-event counts depend on the population monitored, the observation period, definitions and reporting practices. A count of zero serious events in a group is a description of the recorded events, not proof that the risk is absent. These safety figures should also be kept separate from the primary heartburn endpoint: they do not provide evidence about symptom relief or the relationship between pH control and symptoms.

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

The registry record establishes that this completed pilot study was designed to examine acid suppression and heartburn symptoms after esomeprazole treatment. It describes randomized assignment to two esomeprazole schedules or placebo, the diary-based definition of relief, the measurement period, and the per-protocol analysis criteria. The record also lists serious and other adverse-event counts by group.

It does not report the primary endpoint counts, a comparison between groups, pH measurement results, or an analysis of the association between pH control and symptoms. As a result, the posted information does not establish how often relief occurred in any group, how groups differed, how precise a difference might be, or whether acid suppression and relief were associated. No treatment conclusion can be drawn from the endpoint description alone.

In general, statistical evidence requires both an estimate and a measure of uncertainty, interpreted in light of the analysis population and methods. A point estimate without uncertainty may be imprecise; a test result without its effect estimate may not convey magnitude. Here, neither kind of primary outcome result is reported in the registry record. The study’s enrollment figure cannot fill that gap, and safety counts cannot be substituted for symptom outcomes.

The pilot designation and stated purpose support treating the study as an investigation of a focused clinical and measurement question. They do not by themselves determine the strength or reliability of the evidence. The registry does not report a sample-size justification, detailed statistical plan, multiplicity handling, or missing-data strategy. Those omissions limit assessment of how the design was intended to support its questions.

Accordingly, the defensible interpretation is about what was planned and how the outcome was defined, rather than about whether a particular regimen produced relief. The registry record does not report enough primary results to judge the direction, magnitude, or precision of the finding.

13. Why This Trial Matters Statistically

This trial raises a useful statistical question about how a biological measure and a patient-reported symptom relate. Acid control is a physiologic concept, while heartburn relief is captured through participant diary responses. The record links these domains in its stated purpose and requires valid pH monitoring for the per-protocol population. That makes the distinction between measuring each outcome and analyzing their association important.

The symptom endpoint illustrates how repeated observations can be converted into a clinically interpretable classification. The diary rule defines relief using a participant’s responses across Day 8 up to Day 14, with an allowance for one day at maximum severity. Such a threshold can aid interpretation, but it also hides variation in symptoms that does not change the final category. Clear reporting of the rule is essential, and the registry provides that definition.

The study also illustrates why design descriptions alone are not outcome evidence. Randomization, masking and a placebo group describe safeguards and comparisons, but readers still need group-specific outcome counts, estimates and uncertainty. Those primary results are not reported in the registry record. Without them, the scientific question remains identifiable, but its answer cannot be assessed from the record.

Finally, the per-protocol definition emphasizes the role of analysis populations. Requiring valid monitoring and diary data can yield a focused analysis set, while potentially excluding some randomized participants. In general, knowing the exclusions and missing-data approach helps readers assess whether the analyzed population reflects the study population. The registry’s population description is incomplete at its final diary criterion, and the number analyzed is not reported.

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 statistical interpretation is the absence of primary outcome counts and group comparisons in the registry record. Although the endpoint definition is detailed, no group-level relief or no-relief results are reported. The pH measurements and the analysis of their relationship with symptoms are also not reported. This prevents assessment of effect direction, magnitude, and precision.

The analysis-population description is incomplete: its final phrase ends after “complete at least 5 days of diary e.” The full diary eligibility rule is therefore not reported in the registry record. The number of participants included in the primary analysis, the outcome denominators, and the reasons for any exclusions are also not reported.

The registry does not report a detailed statistical analysis plan, including the treatment contrast, covariate adjustment, missing-data handling, multiplicity approach, confidence intervals, or p-values. It also does not report the protocol’s sample-size justification or interim-analysis plan. The listed planning assumptions are illustrations and do not establish the trial’s own design rationale.

The safety figures are limited to the listed serious and other adverse-event counts. The other adverse-event terms and death counts are not reported in the registry record. These data do not address the primary symptom endpoint. Together, these reporting gaps mean that the design and endpoint can be described, but the clinical and statistical findings cannot be independently evaluated from the registry information recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pilot Study To Investigate The Association Between Acid Control And Heartburn Symptoms After Proton Pump Inhibitor Treatment — NCT02708355.
• Registry record last updated 2017-04-19; status last verified 2017-03.
• Results first posted 2017-04-19.
• 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.

18. Record Summary

NCT02708355 is a completed Phase IV, randomized, quadruple-masked, parallel pilot study described as multicenter and placebo-controlled. Enrollment is listed as 55. The recorded study start is 2016-01, and primary completion is 2016-04. The study concerned frequent heartburn and compared esomeprazole 20 mg twice daily, esomeprazole 20 mg once daily with evening placebo, and placebo.

The primary outcome counts participants with and without relief of 24-hour heartburn during Day 8 up to Day 14, using a specified diary rule. The primary outcome counts, pH results, group comparison, and analysis of the stated association are not reported in the registry record. The safety record lists 0 serious adverse events in each group and other adverse-event counts of 3, 1 and 2, respectively. The full per-protocol diary criterion and detailed statistical methods are not reported in the registry record.