Efficacy and Safety Study of Esomeprazole 20mg qd vs Ranitidine 150mg Bid in Patients With an NSAID-induced Gastric Ulcer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Esomeprazole 20mg qd vs Ranitidine 150mg Bid in Patients With an NSAID-induced Gastric Ulcer (NCT00401752), a randomized phase 3 study. The primary outcome is The Percentage of Subjects Whose Gastric Ulcer(s) (GUs) Was (Were) Healed at Week 4 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily Non-steroidal Anti-inflammatory Drug (NSAID)Therapy..

2. Clinical Question

3. Trial Design

The registry record describes a phase 3, randomized, double-blind, double-dummy, parallel-group comparative study. The official title identifies the study as multicenter and specifies an 8-week treatment period. Participants were assigned to esomeprazole 20 mg once daily or ranitidine 150 mg twice daily, while daily NSAID use continued. The registry lists an enrollment of 397 and a completed status.

The primary outcome was the percentage of participants whose gastric ulcer had healed at week 4. Healing meant that no gastric ulcer was present. Other registered outcomes included gastric-ulcer healing at week 8, heartburn resolution, duodenal-ulcer healing, combined gastric and duodenal ulcer healing, and adverse events. The registry record does not report outcome values for every registered secondary measure in the posted results.

The primary comparison uses endpoint-specific denominators of 106 for esomeprazole and 111 for ranitidine. These differ from the enrollment figure. The registry record does not explain the difference or state which analysis population produced those denominators. Randomization and masking describe important aspects of the design, but do not by themselves establish how missing observations, protocol deviations, or analysis populations were handled.

The registry record does not report the original sample-size justification, the planned statistical analysis, or whether interim analyses were conducted. It also does not report a formal test of whether the groups were equivalent or noninferior. The results should therefore be read as the posted between-group outcome estimates and their uncertainty, rather than as evidence of a prespecified equivalence conclusion.

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: Total 397 patients from 24 centers in China were enrolled. 178 patients were not randomised due to unwillingness to continue the study or development of any exclusion criteria, etc. Total 219 patients were randomised, 217 patients were included in ITT population.

Overall Study

Reasons for not completing this 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.

6. Primary Endpoint

The registry lists the primary outcome as The Percentage of Subjects Whose Gastric Ulcer(s) (GUs) Was (Were) Healed at Week 4 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily Non-steroidal Anti-inflammatory Drug (NSAID)Therapy., measured over 4 weeks.

The primary endpoint is the percentage of participants whose gastric ulcer was healed at week 4. In the registry definition, a healed ulcer means absence of gastric ulcers. This makes the endpoint a binary status at a fixed follow-up: each participant is classified according to whether the ulcer is absent at that assessment, and the reported group result is a proportion.

A proportion is useful for a clinical trial comparison because it expresses how often the specified outcome was observed in each treatment group. The between-group risk difference then describes the absolute contrast between those proportions. That contrast is distinct from a relative measure, which compares one group’s proportion with the other’s.

The fixed-time endpoint is relevant to the study question because the registry aimed to assess ulcer healing after treatment while daily NSAID therapy continued. It does not show when healing occurred during follow-up, whether healing persisted after treatment, or what happened beyond the registered assessments. The primary endpoint is gastric-ulcer healing; results for heartburn or duodenal ulcers address different outcomes and should not be treated as substitutes for it.

The registry record describes the outcome as a percentage of participants but does not report a detailed analysis-population definition or explain how missing week-4 assessments were handled. Those details matter when interpreting a proportion, because the estimate depends on which participants are included and how unavailable outcome information is treated.

7. Results Posted in the Registry

• Ranitidine: 59.5% (66/111) versus 59.4% (63/106) on control; risk difference 0.0 percentage points (95% CI -13.0 to 13.1), risk ratio 1.00 (0.80–1.25); unadjusted two-proportion z-test p = 0.997.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The Percentage of Subjects Whose Gastric Ulcer(s) Was (Were) Healed at Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ranitidine: 73.9% (82/111) versus 81.1% (86/106) on control; risk difference -7.3 percentage points (95% CI -18.3 to 3.8), risk ratio 0.91 (0.79–1.05); unadjusted two-proportion z-test p = 0.201.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ranitidine and the control. The interval gives the range of effects that remain compatible with the data.

The Resolution of Heartburn Symptoms at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ranitidine: 97.3% (108/111) versus 100.0% (106/106) on control; risk difference -2.7 percentage points (95% CI -5.7 to 0.3), risk ratio 0.97 (0.94–1.00); unadjusted two-proportion z-test p = 0.088.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ranitidine and the control. The interval gives the range of effects that remain compatible with the data.

The Percentage of Participants Whose Duodenal Ulcer(s) (DUs) Was (Were) Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ranitidine: 81.8% (18/22) versus 93.3% (14/15) on control; risk difference -11.5 percentage points (95% CI -32.0 to 9.0), risk ratio 0.88 (0.69–1.11); unadjusted two-proportion z-test p = 0.314.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ranitidine and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary question to a later gastric-ulcer assessment, symptom resolution, duodenal-ulcer healing, combined ulcer healing, and adverse events. The posted secondary results do not all address the same clinical or statistical quantity: some are fixed-time healing proportions, while others concern symptoms or safety. They should therefore be read as separate outcome descriptions rather than pooled into a single measure of treatment effect.

Across the posted healing and symptom outcomes, point estimates generally lean numerically toward esomeprazole, but the evidence is not uniform in precision. The primary week-4 gastric-ulcer comparison remains the central registered result and showed very similar observed proportions. Secondary findings may add context, but they do not overturn or independently validate that primary comparison.

Unadjusted secondary results carry less weight because several outcomes and assessments are considered. When many comparisons are examined, some may look notable by chance even when there is no underlying difference. General statistical principle: multiplicity procedures can control the overall false-positive risk, but the registry record does not report such a procedure. It also does not report a complete hierarchy or analysis plan for the secondary endpoints.

The record lists five secondary outcomes, but the posted results do not include values for every registered measure. It gives no reported analyses for the posted secondary comparisons. Accordingly, the secondary pattern is descriptive and should not be interpreted as a formal collection of confirmatory tests. In particular, the smaller duodenal-ulcer denominators make those estimates less informative than the primary endpoint and warrant caution about their precision. The record does not report enough detail to determine whether these secondary outcomes were prespecified for formal hypothesis testing or how missing assessments were handled.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• The Percentage of Subjects Whose Gastric Ulcer(s) Was (Were) Healed at Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.
• The Resolution of Heartburn Symptoms at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.
• Percentage of Participants With the Occurance of Any Adverse Event.
• The Percentage of Participants Whose Duodenal Ulcer(s) (DUs) Was (Were) Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.
• The Percentage of Participants Whose GU(s) and DU(s) in Combination Were Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: a participant either met the registry definition of healing at week 4 or did not. The group percentages summarize the proportion meeting that definition. The registry reports a risk difference for the comparison, which expresses the absolute contrast between the two proportions. Its estimate is close to zero, consistent with the nearly identical posted group percentages. The reported unadjusted p value is 0.997.

What does a confidence interval communicate?

In general, a confidence interval describes the range of effect estimates that are reasonably compatible with the observed data under the method used to construct it. It communicates uncertainty around an estimate; it is not a range containing a known true value with certainty. For the primary risk difference, the posted interval extends to both sides of zero. That means the data do not pin down the direction of the difference. The interval should be considered alongside the point estimate rather than replaced by a binary reading of the p value.

How should the p value be read?

In general, a p value describes how unusual data at least as incompatible with a stated null hypothesis would be if that hypothesis and the test assumptions were correct. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of a result. The registry reports an unadjusted p value for the primary comparison. The registry record does not report the full test specification, adjustment for covariates, or a prespecified decision threshold, so the value should not be presented as proof of equivalence or as a complete account of the planned analysis.

What do the denominators mean?

The primary endpoint is reported for 106 participants in the esomeprazole group and 111 in the ranitidine group. These are the denominators attached to the posted primary outcome, not the registry enrollment figure. The registry record does not identify whether these denominators reflect all randomized participants, an evaluable subset, or another analysis population. It also does not state how missing outcome assessments were treated. Those omissions limit assessment of possible bias from exclusions or unavailable outcomes.

What can be inferred from randomization and masking?

Random allocation is intended to make treatment groups comparable with respect to measured and unmeasured characteristics on average, while masking is intended to reduce the influence of treatment knowledge on care, reporting, and assessment. These are design protections, not guarantees that all sources of bias are absent. The registry identifies the study as randomized, double-blind, double-dummy, and parallel-group, but does not report the sequence-generation procedure, allocation concealment details, success of masking, or analysis population. The registry record also does not report protocol deviations or a missing-data strategy.

Why do unadjusted analyses need care?

An unadjusted comparison describes the observed groups without accounting for additional variables in the statistical model. That can be a straightforward summary, but it may not match a planned adjusted analysis and does not resolve concerns about missing information or multiple outcomes. The primary comparison is reported as unadjusted. The registry record lists no reported analyses for the secondary outcomes. Therefore, the available results do not establish whether adjusted models were performed or whether the posted estimates represent all analyses that were planned.

How should the planning illustrations be understood?

The sample-size planning assumptions use a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The effect to be detected is framed as a stated fraction of the observed effect. General statistical principle: smaller effects are harder to distinguish from random variation and therefore require more participants under otherwise comparable assumptions. The planning figures are illustrations derived from the observed effect; they are not the original trial’s sample-size rationale. The registry record does not report that rationale, the assumptions used when designing the trial, or whether a formal interim analysis was planned.

General statistical principle: when a result is based on a binary endpoint, the precision of the estimated proportion and the between-group contrast depends on the amount of outcome information, not simply on the overall enrollment label. The endpoint-specific denominators and the width of the confidence interval are consequently important parts of interpretation. Neither a p value nor a planning calculation can substitute for a clear report of how participants and missing assessments were handled.

11. Confidence Intervals and Precision

The primary point estimates are 59.4 for esomeprazole and 59.5 for ranitidine. Their closeness conveys the observed contrast, while the confidence interval conveys how much uncertainty remains about the underlying between-group difference. The reported interval includes zero and extends to values on either side of it. Thus, the result does not establish which group has the higher underlying healing proportion, even though the observed percentages are close.

In general, a confidence interval is more informative than a point estimate alone because it shows both the estimated effect and its precision. A narrow interval would indicate that the data constrain the plausible effect more tightly; a wider interval would leave more uncertainty. The interval should not be reduced to the statement that there was “no effect.” It allows for a range of effects, including no difference, and the registry record does not report a prespecified equivalence margin against which to judge that range.

The primary endpoint denominators are 106 and 111. The record does not explain how these relate to enrollment or how unavailable outcomes were handled. Confidence-interval interpretation does not remove that limitation: the interval quantifies statistical uncertainty under the analysis used, but it cannot account for an unreported missing-data mechanism or an unclear analysis population.

The same caution applies to secondary estimates. Their interval widths and whether intervals cross zero indicate how uncertain each contrast is, but multiple outcomes raise additional interpretive concerns. The registry record does not report multiplicity adjustment. Taken together, the primary result is a precise description of the posted proportions, but it does not yield a sharply determined treatment difference or establish equivalence.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations are expressed as participants per arm for 80% power and participants per arm for 90% power. They are not total events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

In plain language, the 80% power column gives the illustrative number of participants in each arm under which the specified planning method would have an 80% chance of detecting the assumed effect if that effect were present and the assumptions held. The 90% column uses a higher target chance of detection and consequently gives a larger planning requirement under the same general setup. These are prospective planning quantities, not a measure of what the completed trial achieved.

The illustrations include scenarios based on 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect where those calculations are posted. A smaller assumed effect requires more participants because it is harder to distinguish from random variation. That relationship is a general statistical principle, and the listed scenarios illustrate it under the stated planning assumptions.

These figures are not observed power. They are planning illustrations computed from observed effects, not a reconstruction of the study’s original design or a retrospective judgment that the trial was adequately powered. Because the effect used in the illustration comes from the observed results, the calculations should not be treated as independent evidence for or against the primary finding. The registry record does not report the original design calculation, its target effect, or its chosen power.

13. How the Sample Size Is Derived

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes, including multiple outcome types and follow-up assessments. It does not report whether a multiplicity strategy was planned or used. Without that information, the secondary comparisons should be treated as descriptive rather than as a set of independent confirmatory tests. In general, examining multiple outcomes increases the chance that at least one comparison will appear unusual by chance; adjustment or a prespecified testing hierarchy can address that concern, but neither is reported in the registry record.

The posted primary comparison includes an unadjusted p value. The registry record does not report the full statistical analysis plan, including any planned covariate adjustment, a hierarchy for testing, sensitivity analyses, or rules for interpreting the results. It also reports no analyses for the secondary outcomes. It is therefore not possible to establish from the record whether the posted analyses match all planned analyses or whether unreported analyses were conducted.

Missing-data handling and analysis populations are also not reported. The primary outcome denominators are 106 and 111, whereas enrollment is listed as 397. The record does not explain the relationship between those figures, identify the randomized or evaluable populations used for each outcome, or describe any exclusions. It does not state whether missing assessments were imputed, treated as failures, or omitted from the calculation. No such handling should be assumed.

These reporting gaps do not by themselves show that the results are biased. They do limit independent assessment of how robust the estimates are to analysis choices and unavailable outcome data. A full interpretation would benefit from a clear account of the analysis populations, participant flow, missingness, prespecified statistical methods, and any multiplicity control. Those details are not reported in the registry record.

15. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastric cancer (1.9%), gu haemorrhage (0.9%), erythrodermic psoriasis (0.9%).

The registry reports serious adverse events affecting 2 participants in the esomeprazole group and 2 in the ranitidine group. The listed at-risk counts are 107 and 110, respectively. The record also names gastric cancer, GU haemorrhage, and erythrodermic psoriasis among the top serious-event terms, with the listed percentages of 1.9%, 0.9%, and 0.9%. The registry record does not clarify the full relationship between those terms, treatment groups, and the serious-event counts, so they should not be assigned to a group without further information.

Other adverse-event counts are listed as 13 for esomeprazole and 16 for ranitidine. These are distinct from the serious adverse-event counts and should not be combined with them. Death counts are not reported in the registry record. The safety information is a descriptive account; the record does not provide a statistical comparison, detailed event-level assessment, or enough information to infer that the treatments have equivalent safety profiles. Differences in observed counts alone do not establish a causal safety difference.

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

The posted primary result says that the observed proportion of participants classified as having a healed gastric ulcer at week 4 was 59.4 with esomeprazole and 59.5 with ranitidine. The comparison estimate is close to zero, and its confidence interval includes zero. This describes the observed outcomes in the groups represented by the endpoint denominators; it does not establish that the treatments are equivalent, that their effects are identical, or that either treatment is superior.

The study addressed a specific setting: participants with NSAID-associated gastric ulcers who continued daily NSAID therapy. The registry lists both gastric-ulcer and other outcomes, but the primary result speaks only to the registered definition of gastric-ulcer healing at the specified assessment. It does not establish the timing of healing, persistence after follow-up, or outcomes outside the registered assessments.

The secondary findings provide additional descriptions, but they should not be used to make a broad overall claim. Different endpoints measure different things, and the registry record does not report multiplicity control or the full planned analysis. The safety counts are also descriptive and do not establish comparative safety.

In general, a failure to demonstrate a difference is not proof that no meaningful difference exists. Establishing equivalence or noninferiority requires an appropriate design, a prespecified margin, and a suitable analysis. Those elements are not reported in the registry record. The result should therefore be interpreted as an estimate with uncertainty, not as a definitive statement that the two treatments have the same effect.

The registry record also does not explain why the primary denominators are smaller than enrollment or how missing outcome data were handled. These omissions limit assessment of the completeness and representativeness of the posted endpoint results. The conclusions should remain bounded by the reported population, treatment regimens, outcome definition, and follow-up.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate, an uncertainty interval, and a design question should be considered together. The two posted primary percentages are almost identical, and the estimated risk difference is close to zero. The confidence interval nevertheless extends to both sides of zero, so the result does not identify a clear direction or tightly define the range of plausible differences.

It also demonstrates the distinction between a conventional difference test and an equivalence question. A large unadjusted p value does not establish that two treatments have the same effect. Equivalence requires a prespecified margin and an analysis designed to assess whether the uncertainty is contained within that margin. The registry record does not report such a margin or an equivalence analysis.

The planning illustrations offer another useful statistical lesson: required sample size depends on the effect the study is meant to detect and on the target power and other assumptions. Smaller effects require more participants under otherwise comparable conditions. But planning calculations based on observed effects are not evidence of observed power and are not the same as the trial’s original design justification.

Finally, the record highlights the value of transparent reporting. Endpoint denominators, analysis populations, missing-data handling, multiplicity procedures, and the planned statistical analysis all affect how confidently results can be interpreted. Several of these details are not reported in the registry record. The posted outcome figures remain interpretable as descriptive comparisons, but their broader inferential meaning is limited by those reporting gaps.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint denominators differ from the registry enrollment, and the record does not explain why. It does not specify the analysis population or how missing week-4 assessments were handled. This limits evaluation of whether the posted proportions represent all randomized participants and whether exclusions or unavailable outcomes could have influenced the estimates.

The registry record does not report the original sample-size justification, the detailed statistical analysis plan, or whether interim analyses were conducted. It also does not report an equivalence or noninferiority margin, multiplicity adjustment, or a complete testing hierarchy. These gaps matter because the primary result is a comparison without a clear stated framework for interpreting an absence of evidence of difference, while several secondary endpoints are also posted.

Some secondary outcomes have relatively small endpoint denominators, particularly the duodenal-ulcer outcome. Estimates based on limited outcome information can be imprecise, and the record does not report a separate analysis plan or missing-data approach for those outcomes. The registry also does not provide values for every registered secondary measure.

The posted information is limited to the described outcomes and assessments. It does not provide a detailed account of participant flow, protocol deviations, treatment adherence, or the relationship between the serious-event terms and treatment groups. These omissions do not establish that a problem occurred, but they restrict independent evaluation of the results and their generalizability beyond the study population and setting.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Esomeprazole 20mg qd vs Ranitidine 150mg Bid in Patients With an NSAID-induced Gastric Ulcer — NCT00401752.
• Registry record last updated 2010-07-08; status last verified 2010-06.
• Results first posted 2010-07-08.
• 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.

22. Record Summary

The registry describes a completed phase 3 randomized, double-blind, double-dummy, parallel-group comparison of esomeprazole 20 mg once daily and ranitidine 150 mg twice daily in participants with NSAID-associated gastric ulcers who continued daily NSAID therapy. The listed enrollment is 397, and the official title describes an 8-week study.

The primary outcome was gastric-ulcer healing at week 4, defined as absence of gastric ulcers. Posted healing percentages were 59.4 for esomeprazole and 59.5 for ranitidine; the reported unadjusted p value was 0.997, and the confidence interval for the risk difference includes zero. The finding describes similar observed proportions but does not establish equivalence.

Secondary outcomes and adverse-event information add context, but multiplicity procedures, missing-data handling, analysis populations, and the original sample-size rationale are not reported in the registry record.