Efficacy of Pantoprazole in Patients Older Than 12 Years With Reflux Associated Sleep Disorders (PULS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Pantoprazole in Patients Older Than 12 Years With Reflux Associated Sleep Disorders (PULS) (NCT00562094), a registered phase not stated study. The primary outcome is Assessment of the Severity of Sleep Disturbances.

2. Clinical Question

The study title identifies sleep disorders associated with reflux as its particular focus. Other listed outcomes concern heartburn, eructation or acid eructation, epigastric complaints or pain, fullness or abdominal distension, and final-visit assessments of efficacy and tolerability. The registry record lists eight outcome measures in total, but does not provide numerical results for the primary outcome or a comparative treatment effect. The clinical question is therefore descriptive in the posted record: it concerns physician-assessed symptom severity over the observed visits, rather than a documented randomized estimate of pantoprazole versus a control.

3. Trial Design

The registry record identifies the study as PULS, titled “Efficacy of Pantoprazole in Patients Older Than 12 Years With Reflux Associated Sleep Disorders.” It lists erosive gastroesophageal reflux disease and non-erosive reflux disease as the conditions. The study summary describes an evaluation of pantoprazole 20 mg/40 mg for 14 days, with special focus on reducing symptomatic sleep disorders.

The recorded intervention is pantoprazole. The record does not describe dose allocation, a control intervention, or a treatment allocation procedure. It explicitly notes that allocation was not stated and that the arms are not a like-for-like control comparison. Consequently, the record does not support treating the study as a randomized comparison or interpreting any outcome as a randomized contrast.

Enrollment is listed as 8616. The registry status is completed, with a start of 2007-10 and primary completion of 2009-04. These dates and the enrollment figure describe the registered study, but do not establish how many participants contributed to each outcome assessment. Outcome-specific denominators are not reported in the registry record.

The primary outcome is the physician’s assessment of sleep-disturbance severity, recorded at the first and last visits. The endpoint description gives a median of 18 days to the last visit. This assessment timing is distinct from the 14-day treatment duration stated in the study summary; the registry record does not explain the difference between those descriptions. It also does not report a detailed protocol, a sample-size justification, or further design features such as blinding or a prespecified control group.

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: All patients included and treated, intention to treat, missing values not imputed

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.

6. Primary Endpoint

The registry lists the primary outcome as Assessment of the Severity of Sleep Disturbances, measured over first and last visit (after a median of 18 days).

The primary endpoint is titled “Assessment of the Severity of Sleep Disturbances.” It is a physician assessment on a scale where 1 means none, 2 mild, 3 moderate, and 4 severe. The registry describes assessments at the first and last visits, with the last visit occurring after a median of 18 days. The stated unit is percentage of participants, while the parameter is listed as a number. Numerical endpoint values are not reported in the registry record, so the distribution across severity levels and any change between visits cannot be reconstructed from the posted results.

Sleep disturbance is used as the primary focus because the study summary specifically identifies symptomatic sleep disorders associated with reflux as the outcome of interest. A graded scale can convey severity rather than merely recording whether a symptom is present or absent. In general, ordinal severity categories preserve an ordering, but the distance between adjacent categories is not necessarily equal. For that reason, interpretation depends on how the categories are summarized and analyzed. The registry record does not report the analysis method or explain how the scale was converted into the stated percentage unit.

The recorded analysis population is all patients included and treated, labeled intention to treat, with missing values not imputed. That description indicates that missing outcome values were not filled in by an imputation procedure, but the numbers assessed at each visit are not reported in the registry record. Without those counts and the actual category results, endpoint precision and the extent of missingness cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the severity scale represent?

The primary assessment uses four ordered categories: none, mild, moderate, and severe, coded from 1 through 4. This is an ordinal scale. Ordinal means the categories have a meaningful order, while the gaps between neighboring categories are not necessarily equal. In general, a shift from severe to moderate should not automatically be treated as numerically equivalent to a shift from mild to none unless the analysis makes and supports that assumption.

The registry lists the outcome unit as percentage of participants and the parameter as a number. It does not explain how the physician ratings were summarized to produce that unit, whether percentages refer to any particular category or grouping, or which statistical method was used. The actual values are not reported in the registry record. It is therefore not possible to say which severity categories were most common or how the distribution changed over visits.

What would a confidence interval tell a reader?

In general, a confidence interval describes the range of values reasonably compatible with an estimate under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone establishes that a difference is clinically important. For this study, an outcome estimate and its confidence interval are not reported in the registry record. No claim about the precision of a change in sleep-disturbance severity can therefore be made.

Statistical significance and precision are related but distinct ideas. A test result addresses compatibility with a specified null hypothesis under a model; an interval communicates uncertainty about the estimated quantity. Neither can replace a clear comparison design. Since allocation and a like-for-like control comparison are not documented, a hypothetical within-group test would not establish what would have happened to comparable patients without the intervention.

Why does the comparison design matter?

In general, random allocation can help make treatment groups comparable with respect to both measured and unmeasured characteristics. The registry record does not report randomization and explicitly warns against treating the arms as a like-for-like control comparison. It is not appropriate to assume that a control group existed or that allocation created comparable groups. A before-and-after description can document observed change, but by itself it cannot isolate the cause of that change.

The registry lists pantoprazole as the intervention and describes pantoprazole 20 mg/40 mg for 14 days in the study summary. It does not report how dose groups were formed, whether they were compared, or whether the analysis accounted for differences between them. Dose-specific effects and comparisons are not reported in the registry record.

How should missing observations be considered?

The registry labels the population as all patients included and treated, intention to treat, and says missing values were not imputed. In general, an analysis that does not impute missing outcomes uses observed information rather than filling in absent measurements with model-based values. This does not by itself explain why values are missing or whether participants with missing outcomes differ from those with observed outcomes. Such differences can affect interpretation.

The record does not give the number with a recorded first-visit or last-visit assessment, the extent or reasons for missingness, or an analysis of sensitivity to missing values. As a result, the reader cannot assess how representative the observed outcome assessments are of the enrolled population. The phrase intention to treat is the registry’s population label; further operational details about that analysis population are not reported in the registry record.

What is not documented about the statistical plan?

The registry lists 0 analyses and does not report a detailed statistical analysis plan, model, test, or adjustment procedure for the primary endpoint. It also does not report a sample-size justification or interim-analysis plan. General statistical considerations—such as whether a model accounts for repeated measurements or how ordinal categories are handled—cannot be attributed to this study without documentation.

The record lists eight outcome measures. When several outcomes are examined, multiplicity can arise because repeated testing increases the chance of finding an apparently notable result by chance. In general, prespecified prioritization or statistical adjustment can address aspects of this issue. The registry record does not describe a multiplicity procedure, and the numerical outcome results are not reported. No significance claims can be evaluated from the record.

A sample-size calculation is a planning tool based on assumptions about the target effect, variability, allocation, and statistical method. It is not an observed result and does not establish the precision of the actual outcome estimate. A sample-size justification for the trial is not reported in the registry record. The registry’s enrollment figure should therefore be understood as enrollment, not as evidence of a particular level of power or precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists eight outcome measures, including sleep-disturbance severity and several reflux-related symptoms, as well as final-visit efficacy and tolerability assessments. Examining multiple outcomes raises a general multiplicity issue: the more statistical tests conducted, the greater the opportunity for one result to appear notable by chance, even when no effect exists. This is a general statistical concern, not a claim about the analysis conducted in this study.

The record lists 0 analyses and does not report whether outcomes were prioritized in a statistical plan, whether tests were adjusted for multiplicity, or whether any results were prespecified. A multiplicity strategy is therefore not reported in the registry record. Since numerical results and analysis-level tests are also not reported, no significance findings can be independently interpreted from this record.

The primary analysis population is described as all patients included and treated, intention to treat, with missing values not imputed. The record does not describe the number of missing primary assessments, the reasons for missingness, or whether the first- and last-visit observations were available for the same participants. It also does not provide outcome-specific denominators or sensitivity analyses. These gaps limit assessment of whether the observed participants represent the enrolled population and how missing measurements may affect interpretation.

The population label and missing-data statement do not supply enough detail to reconstruct the analysis. The registry record does not report a protocol definition of the analysis set, rules for incomplete observations, or any imputation method. Readers should not assume that missing participants had no symptoms, that missingness was evenly distributed, or that the stated population label resolves these uncertainties.

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 0.01% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchial carcinoma (0.0%), renal failure acute (0.0%).

The safety figures list 8616 participants at risk for serious adverse events and 2 affected. For other adverse events, the record lists 8616 at risk and 11 affected. These are counts reported for the pantoprazole group, not comparative estimates. Allocation was not stated, and a like-for-like control comparison is not documented, so the figures alone cannot show whether event occurrence differed from what would have happened under another treatment or no treatment.

The serious adverse event terms shown include bronchial carcinoma and acute renal failure, each with a displayed percentage of 0.0%. Those are the percentages as recorded; the registry record does not provide event counts by term in this listing. A rounded percentage of 0.0% should not be read as proof that no event occurred.

Deaths are listed as null. This means a death count is not reported in the registry record; it should not be interpreted as zero deaths. The record also does not provide further details such as event timing, severity, relatedness assessments, or follow-up duration for the safety counts. These figures describe the posted safety entries, not a causal safety comparison.

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

The record documents a completed evaluation of pantoprazole in patients with erosive or non-erosive reflux disease, with sleep-disturbance severity as the primary outcome. It gives the assessment scale, the first- and last-visit timing, an enrolled population of 8616, and the study summary’s description of pantoprazole 20 mg/40 mg for 14 days. These details establish the registered focus and measurement approach.

They do not establish the primary outcome result. Numerical values for the sleep-disturbance assessment are not reported in the registry record, and the record lists 0 analyses. The direction, size, and precision of any observed change therefore cannot be described. Outcome names and enrollment totals do not substitute for results.

The record also does not document a randomized control comparison. It says allocation was not stated and cautions that the arms are not a like-for-like control comparison. Consequently, even a reported change over time would not by itself establish that pantoprazole caused the change. In general, causal interpretation depends on a suitable comparison and a design and analysis that address other explanations for observed differences.

The listed safety counts are descriptive entries for the pantoprazole group. They do not quantify a relative risk against a control, and the missing death entry is not evidence of zero deaths. Further detail about the events and their assessment is not reported in the registry record.

The most defensible reading is that the registry describes the intended clinical focus and selected outcome definitions, but does not contain enough reported results to judge the observed sleep-severity pattern or estimate a treatment effect. No conclusion that pantoprazole did or did not improve symptoms follows from the information recorded.

13. Why This Trial Matters Statistically

This study is statistically notable as a registry record of a large enrollment focused on a symptom outcome that is measured on an ordered severity scale. The primary focus is sleep disturbance associated with reflux, rather than a laboratory measure or a single yes-or-no symptom. A graded physician assessment can retain information about severity, but its interpretation depends on how the categories are summarized and analyzed.

The record also illustrates why design information is essential alongside an outcome definition. It identifies pantoprazole as the intervention, but says allocation was not stated and that the arms are not a like-for-like control comparison. The existence of an outcome assessment at two visits does not create a randomized treatment contrast. Statistical analyses cannot, on their own, remove all the uncertainty created by an undocumented comparison design.

Another important issue is the gap between a clearly stated measurement plan and the absence of numerical endpoint results. The record identifies the rating categories, visit timing, and analysis population label, yet does not report the distribution of ratings, outcome denominators, or an estimate of change. Without those elements, readers cannot assess precision, missingness, or the magnitude of any observed pattern.

The registry lists multiple outcomes, which makes prespecification and multiplicity considerations relevant in general. However, it reports 0 analyses and no multiplicity strategy. The record therefore offers a useful example of how outcome definitions and enrollment figures can be present while core information for statistical interpretation remains unavailable.

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 primary outcome’s numerical results are not reported in the registry record. Without values at the first and last visits, there is no basis for describing the observed distribution of severity, a change over time, or its precision. The record also does not give the number assessed at each visit, so the outcome-specific denominator cannot be established from the endpoint description.

The allocation method is not stated, and the record cautions that the arms are not a like-for-like control comparison. A control treatment and a randomized contrast are not documented. This prevents interpretation as a randomized estimate of treatment effect and limits causal conclusions even if within-group outcome values were available.

The registry summary describes pantoprazole 20 mg/40 mg for 14 days, but dose assignment and dose-specific results are not reported. The endpoint is assessed at the first and last visits, with a median of 18 days to the last visit; the record does not explain how this timing relates to the stated treatment duration.

Further limitations include the absence of outcome-specific missing-data counts, reasons for missingness, and sensitivity analyses. Although the analysis population is labeled intention to treat and missing values are not imputed, the operational details are not reported. The statistical analysis plan, model, test, sample-size justification, and multiplicity approach are also not reported in the registry record. The listed safety entries do not provide a control comparison, and deaths are listed as null rather than as a numerical count.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy of Pantoprazole in Patients Older Than 12 Years With Reflux Associated Sleep Disorders (PULS) — NCT00562094.
• Registry record last updated 2012-05-08; status last verified 2012-05.
• Results first posted 2010-09-24.
• 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

PULS is registered as a completed study of pantoprazole in patients older than 12 years with reflux-associated sleep disorders. The record lists erosive gastroesophageal reflux disease and non-erosive reflux disease, enrollment of 8616, a start of 2007-10, and primary completion of 2009-04. The study summary describes pantoprazole 20 mg/40 mg for 14 days.

The primary outcome is physician-assessed sleep-disturbance severity, measured on a scale from none to severe at the first and last visits, with a median of 18 days to the last visit. Numerical primary-outcome results are not reported in the registry record. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. It lists 0 analyses and does not report a detailed statistical plan, outcome-specific missingness, or a sample-size justification.