Rabeprazole Extended-Release, 50 mg, Versus Esomeprazole, 40 mg, for Healing and Symptomatic Relief of Moderate to Severe Erosive Gastroesophageal Reflux Disease (GERD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rabeprazole Extended-Release, 50 mg, Versus Esomeprazole, 40 mg, for Healing and Symptomatic Relief of Moderate to Severe Erosive Gastroesophageal Reflux Disease (GERD) (NCT00658775), a randomized phase 3 study. The primary outcome is Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks.

2. Clinical Question

The trial’s stated purpose was to investigate healing, symptom relief, and safety for the two treatments in moderate to severe erosive GERD. The primary endpoint focuses on endoscopic healing; a listed secondary outcome concerns diary-recorded sustained resolution of heartburn by week 4. These are distinct clinical measures: an endoscopic assessment evaluates the esophageal mucosa, whereas a diary-based outcome captures participants’ reported symptoms over time.

The registry record identifies the endpoint population but does not report the number of participants achieving healing in either group, the treatment contrast, or its uncertainty. It therefore does not establish from the posted results whether the groups differed, nor how precisely any difference was estimated. The clinical question can be stated from the trial’s design and endpoint, but its answer cannot be recovered from the numerical results available in the registry record.

3. Trial Design

NCT00658775 is recorded as a completed phase 3 study. It used randomized allocation, double masking, and a parallel-group model to compare rabeprazole extended-release 50 mg with esomeprazole 40 mg. The registry lists enrollment of 1069 participants. The study began in 2008-02, and primary completion was recorded as 2009-09.

A randomized design assigns participants to treatment groups by chance, which is intended to reduce systematic differences between groups at the time of assignment. In general, double masking means that treatment knowledge is withheld from participants and relevant study personnel, although the registry record does not specify exactly who was masked or how masking was maintained. A parallel design means participants are assigned to a treatment group and assessed under that group’s treatment rather than crossing between treatments.

The registry record lists rabeprazole sodium and esomeprazole as the interventions. The arm-description fields contain no additional descriptions. The stated study purpose includes efficacy, symptom relief, and safety, while the primary endpoint is the percentage of participants with endoscopically confirmed healing by week 8. The record also lists diary-recorded sustained heartburn resolution by week 4 as a secondary outcome.

The primary endpoint specifies baseline and week 8 as its timeframe and defines the population as randomized subjects who received at least one dose of study drug. The registry record does not report the allocation ratio, details of the randomization sequence, concealment procedures, masking procedures, treatment duration beyond the endpoint timeframe, or additional eligibility criteria. It also does not report the protocol’s sample-size justification or a detailed analysis plan. Those features should not be inferred from the randomized, double-blind, parallel description 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.

Before assignment: Out of 1069 participants who were randomized, 1065 participants received study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population - all randomized subjects who received at least 1 dose of study drug.

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 Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks, measured over Baseline and Week 8.

The primary endpoint is the percentage of participants with eGERD who achieved endoscopically confirmed healing by week 8. The registry describes healing in relation to improvement from baseline in Los Angeles (LA) classification grade C or D esophagitis. The LA classification uses the extent and pattern of mucosal breaks, or erosions, in the esophagus. Grade C involves breaks continuous between the tops of at least two mucosal folds but involving less than 75% of the esophageal circumference. Grade D involves breaks involving at least 75% of the circumference. The description also defines grades A and B and notes that mucosal breaks are absent when the condition is classified as not present.

Endoscopy provides an assessment of visible esophageal injury rather than relying solely on symptom reports. That makes healing a clinically relevant measure for a trial focused on erosive disease. It also differs from symptom relief: participants’ experience of heartburn and endoscopic appearances need not be treated as the same outcome. The listed secondary outcome, sustained diary-recorded resolution of heartburn by week 4, addresses symptoms from the participant’s perspective.

The endpoint is expressed as a percentage of participants, so its interpretation depends on the number meeting the healing definition and the population used as the denominator. The registry identifies the intention-to-treat population as randomized participants who received at least one dose. Numerical healing results by group, the treatment comparison, and a confidence interval are not reported in the registry record. Without those results, the endpoint definition can be described, but the magnitude and precision of any treatment contrast cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. Its statistical purpose is to make treatment assignment independent of participants’ measured and unmeasured characteristics in expectation. This can reduce confounding in a comparison, but it does not guarantee identical groups in a particular trial. The registry records randomized allocation, but it does not report the sequence-generation method, allocation concealment, or checks of baseline balance. Those procedures should not be inferred.

What do double masking and a parallel model mean?

In general, masking is intended to limit the influence of treatment knowledge on participant reports, clinical care, outcome assessment, or analysis. The registry labels the study double-masked but does not say which roles were masked or describe how masking was implemented. In a parallel-group design, participants remain assigned to their treatment group for the comparison rather than receiving both study treatments in sequence. The study is recorded as a randomized, double-blind, parallel phase 3 trial.

How should a percentage endpoint be understood?

The primary endpoint is a percentage of participants who meet the healing definition by week 8. In general, such an endpoint is calculated from the number meeting the criterion and the relevant analysis denominator. The estimate is interpretable only alongside the denominator, the outcome definition, and a measure of uncertainty. The registry describes the primary population as randomized subjects who received at least one dose, but it does not report group-specific endpoint counts or denominators. The healing percentages and treatment contrast are not reported in the registry record.

The endpoint is based on endoscopic improvement from baseline in LA grade C or D esophagitis. In general, use of an explicitly defined clinical threshold helps make outcome classification more reproducible. Here, the record describes the grades by mucosal breaks and their extent. It does not report the detailed assessment procedures, assessor training, adjudication process, or rules for ambiguous examinations. The existence of an endpoint definition does not by itself establish how consistently assessments were performed.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate and can show whether the data are compatible with a range of treatment effects. A narrow interval indicates greater precision than a wide interval under the model used; neither interval width nor the estimate alone determines clinical importance. For a percentage outcome, uncertainty depends on the observed counts and the analysis approach. No confidence interval for healing is reported in the registry record, so precision cannot be evaluated.

What can a p-value say?

In general, a p-value measures how unusual the observed data, or data more extreme, would be if a specified null hypothesis and statistical model were correct. It is not a measure of effect size, clinical importance, or the probability that the null hypothesis is true. A p-value also does not replace the estimate and its confidence interval. No p-value for the primary comparison is reported in the registry record. The record lists 0 analyses, so there is no reported test result to interpret.

Why can over-dispersion matter?

In general, over-dispersion occurs when the variability in data is greater than a chosen statistical model expects. If a model assumes less variability than is present, standard errors may be too small and confidence intervals may be too narrow. Methods that account for extra variability can improve uncertainty estimates when their assumptions fit the data. This trial’s primary endpoint is a percentage outcome, and no outcome model or over-dispersion assessment is reported in the registry record. It would therefore be inappropriate to claim that over-dispersion was present, absent, or addressed.

What does the planning illustration represent?

In general, sample-size planning estimates how many participants may be needed to detect a specified effect under chosen assumptions about significance level, allocation, and statistical method. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; it also describes effects as fractions of an observed effect. These are planning assumptions, not evidence that the trial used them to justify its enrollment. The protocol’s sample-size justification is not reported in the registry record, and no planning sample-size values are reported in the information available.

Planning estimates based on an observed effect are illustrations of what a future design might require under stated assumptions. They are not observed power and do not demonstrate that the completed trial had a particular probability of detecting an effect. Since numerical efficacy findings are not reported, there is no observed treatment effect in the posted results to interpret as the trial’s demonstrated effect.

How should analysis populations be considered?

In general, an analysis population determines which participants contribute to an estimate. An intention-to-treat approach typically retains participants according to randomized assignment, while other analysis sets can apply additional requirements. The registry gives a specific primary-population definition: all randomized subjects who received at least one dose of study drug. The record does not describe whether other populations were used, whether participants were excluded after randomization, or how departures from the intended treatment were handled. Such choices can affect the interpretation of a treatment comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures, including endoscopically confirmed healing by week 8 and diary-recorded sustained resolution of heartburn by week 4. Considering multiple outcomes or time points can raise a multiplicity issue: in general, the more hypotheses tested, the greater the chance of at least one apparently notable result if no adjustment or prespecified testing strategy is used. Whether and how multiplicity was addressed depends on the protocol and statistical analysis plan. Those details are not reported in the registry record.

The record lists 0 analyses and notes that the primary outcome has several categories or time points and was not reduced to a single comparison. It does not report a hierarchy of endpoints, a testing sequence, an adjustment method, or which comparisons were designated confirmatory. No primary-outcome p-value or confidence interval is reported. It is therefore not possible to determine how the registry’s outcome structure relates to any prespecified inferential procedure.

Missing-data handling is also not reported in the registry record. The endpoint timeframe includes baseline and week 8, but the record does not give the number of participants with unavailable endoscopic assessments, reasons for missingness, or assumptions used to analyze missing outcomes. In general, missingness can affect a percentage endpoint if the participants with observed outcomes differ from those without them. Methods such as imputation or sensitivity analysis require explicit assumptions and cannot be attributed to this trial without documentation.

The primary population is defined as randomized subjects who received at least one dose. The record does not report the group-specific number analyzed for healing or clarify how participants lacking a week 8 assessment were treated. As a result, the relationship between the enrollment count, the stated population, and the endpoint denominators cannot be evaluated from the registry record. No particular multiplicity or missing-data method should be inferred.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (0.2%), pneumonia primary atypical (0.2%), head injury (0.2%), oesophageal stenosis (0.2%), cholecystitis (0.2%).

The serious adverse event fields list 3 affected participants among 532 at risk in the esomeprazole 40 mg group and 3 among 526 at risk in the rabeprazole extended-release 50 mg group. Other serious adverse events are listed as 0 among 532 and 0 among 526, respectively. These are the raw counts and denominators recorded for the safety groups; they should be read as descriptive information rather than as a definitive comparison of safety between treatments.

In general, a safety count does not by itself describe the full clinical context, timing, duration, severity profile, or causal relationship of events to study treatment. A comparison also needs a clearly specified analysis and uncertainty assessment. The registry record does not report a statistical comparison of serious adverse events, event rates over time, or a judgment about whether events were related to treatment. Death counts are not reported in the registry record.

The record lists pneumonia, pneumonia primary atypical, head injury, oesophageal stenosis, cholecystitis, and transient ischaemic attack among the serious-event terms, each with a reported percentage of 0.2%. The available information does not identify the treatment group associated with each term or give event counts by term. These term-level percentages should therefore not be assigned to either group or used to infer a between-group difference.

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

The record establishes that a randomized, double-blind, parallel phase 3 study compared rabeprazole extended-release 50 mg with esomeprazole 40 mg for moderate to severe erosive GERD. It identifies endoscopically confirmed healing by week 8 as the primary endpoint and describes the population used for that endpoint. It also lists a symptom outcome and provides limited serious adverse event counts.

Those design details do not answer whether one treatment produced a higher healing percentage. The group-specific healing results, treatment contrast, and uncertainty are not reported in the registry record. The same limitation applies to numerical symptom findings. Without estimates and uncertainty, the posted information cannot establish the direction, size, or precision of an efficacy difference. It also cannot show whether a difference, if one existed, would be clinically important.

In general, a trial’s design and a trial’s results answer different questions. Randomization and masking describe intended safeguards in the comparison, while outcome estimates describe what was observed. A well-described endpoint is useful for understanding what investigators intended to measure, but it is not a substitute for the measured outcomes. Nor does the absence of numerical findings in the registry record establish that there was no effect; it means the effect cannot be assessed from the results reported there.

The serious adverse event counts give a limited account of events recorded in the two groups. They do not provide a complete safety profile, a statistical comparison, or evidence about causation. The listed terms and percentages also lack group attribution in the record information available. Accordingly, the safety fields can be described, but they should not be interpreted as demonstrating a treatment advantage or disadvantage.

The registry record therefore supports a careful account of the trial question, population definition, design, and selected safety counts. It does not support a conclusion about comparative efficacy or a comprehensive comparative safety judgment. Such conclusions require outcome and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why study design, endpoint definition, and result reporting need to be read together. Randomization, double masking, and a parallel-group model identify important features of the intended comparison. The endoscopic healing endpoint specifies a clinical measure and a timeframe, while the separate diary-based secondary outcome addresses reported heartburn symptoms. These details help define what the study set out to examine.

Statistically, however, a design description is not an effect estimate. Readers need the number meeting the endpoint in each group, the analyzed denominators, a treatment contrast, and an uncertainty measure to judge the comparative result. Those numerical efficacy details are not reported in the registry record. The record lists 0 analyses and does not reduce the primary outcome to a single comparison, leaving no reported inferential result to interpret.

The example also highlights the importance of distinguishing endpoint definitions from analysis choices. The registry defines the primary population as randomized participants who received at least one dose, but does not report missing-data handling, endpoint denominators, or the analysis plan. Those details affect how a percentage is estimated and how confidently a treatment contrast can be interpreted. A sample-size planning description, even when it names assumptions, is not the same as a protocol justification or an observed result.

Finally, the serious adverse event fields show why raw counts should be reported with their denominators and interpreted cautiously. The counts are available, but the registry does not provide a statistical comparison or full event-level context. This trial is therefore a useful example of how much can be learned from a registry description—and how the absence of numerical outcome analyses limits conclusions about treatment effects.

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 this trial from the registry record is the absence of numerical efficacy findings. The primary endpoint is defined, but group-specific healing percentages, denominators, a treatment contrast, and uncertainty intervals are not reported in the registry record. The listed secondary symptom outcome also has no numerical findings in the information available.

The record lists 0 analyses and indicates that the primary outcome has several categories or time points and was not reduced to a single comparison. It does not report which specific comparisons were planned, how multiple outcomes or time points were handled, or what inferential methods were used. The statistical analysis plan is not reported in the registry record.

Although the primary population is defined as randomized subjects who received at least one dose, the registry does not report the number analyzed for the endpoint, missing endoscopic assessments, or methods for handling missing data. It also does not report the randomization sequence, allocation concealment, details of masking, or the protocol’s sample-size justification. These omissions limit assessment of implementation and analysis without establishing that any particular procedure was inadequate.

The safety information is limited to serious adverse event counts and a list of event terms with percentages. Death counts are not reported in the registry record. The event-term information does not identify treatment groups, and no comparative safety analysis or causal assessment is reported. Enrollment of 1069 does not resolve these limitations because it does not give the outcome-specific analysis denominators or estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Rabeprazole Extended-Release, 50 mg, Versus Esomeprazole, 40 mg, for Healing and Symptomatic Relief of Moderate to Severe Erosive Gastroesophageal Reflux Disease (GERD) — NCT00658775.
• Registry record last updated 2015-12-21; status last verified 2015-11.
• Results first posted 2015-06-23.
• 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

NCT00658775 is a completed randomized, double-blind, parallel phase 3 study of rabeprazole extended-release 50 mg versus esomeprazole 40 mg for moderate to severe erosive GERD. Enrollment is listed as 1069; the recorded start was 2008-02 and primary completion was 2009-09.

The primary endpoint is the percentage achieving endoscopically confirmed healing by week 8, with the primary population defined as randomized participants who received at least one dose. A secondary outcome concerns diary-recorded sustained heartburn resolution by week 4. Numerical efficacy findings and analyses are not reported in the registry record.

Serious adverse events are listed for 3 of 532 participants receiving esomeprazole and 3 of 526 receiving rabeprazole extended-release; other serious events are listed as 0 in each group. Death counts are not reported in the registry record. The available record supports description of the design and endpoints, but not estimation of comparative efficacy or a complete safety comparison.