Comparative Efficacy & Safety Study of D961H Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With Low-dose Aspirin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparative Efficacy & Safety Study of D961H Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With Low-dose Aspirin (NCT01069939), a randomized phase 3 study. The primary outcome is Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis..

2. Clinical Question

3. Trial Design

This was a Phase III, multinational, multicenter, randomized, double-blind, parallel-group comparative efficacy and safety study. The registry describes the masking as quadruple. Participants were assigned to esomeprazole 20 mg once daily by mouth or placebo once daily by mouth. The record lists 427 participants enrolled and identifies AstraZeneca as the sponsor. The study status is completed.

The trial was designed around continuous low-dose aspirin use among people with a history of gastric and/or duodenal ulcers. The stated aim was to assess whether the study treatment affected time from randomization to occurrence of gastric and/or duodenal ulcers. The registry describes ulcer assessments every 12 weeks after randomization, with analyses at those intervals up to 48 weeks. It also describes the primary outcome as extending to the data cut-off date for an interim analysis, and gives a maximum follow-up period of 48 weeks at that analysis.

The 427 enrolled participants and the 364 included in the interim efficacy evaluation refer to different populations. The registry says participants not taking investigational drug were not included in the efficacy evaluation. It does not give a complete accounting of the difference between enrollment and the efficacy population, or explain how other analysis populations were defined.

Secondary outcomes included change in gastric mucosal lesion degree by the Modified Lanza Scale, reflux esophagitis evaluated using the LA Classification, and changes in symptoms including epigastric pain, heartburn, anorexia, nausea and/or vomiting, and stomach discomfort. These outcomes were assessed up to Week 48, although the wording for one abdominal symptom outcome does not specify an endpoint week. Their results are not reported in the registry record included for this trial. The available information therefore supports a description of the design and registered outcome definitions, but not a complete assessment of comparative efficacy.

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 914 enrolled participants, 430 participants were assigned , but 484 participants were not assigned. The major reasons of no assignment were 'Did not meet eligibility criteria' (462 participants) and 'Voluntary discontinuation by participant' (21 participants). After 366 participants were randomised, the interim analysis was done.

Randomised and Included in the Analyses

Reasons for not completing this period:

At Data Cut Off Date (26 Feb 2011)

Analysis population for the primary outcome, as defined in the registry: Participants not taking investigational drug were not included. In total 364 participants were included in the efficacy evaluation at the interim analysis. 24 of the 364 total participants had an occurrence of gastric and/or duodenal ulcers by the 48-week assessment.

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 Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis., measured over From randomisation to up to 48 weeks (Maximum follow-up period at the interim analysis).

The primary outcome is described as time from randomization to occurrence of gastric and/or duodenal ulcers, with a maximum follow-up period of 48 weeks at the interim analysis. Assessments for ulcer occurrence were performed every 12 weeks, and the registry says numbers of participants with recurrence were analyzed at those intervals up to 48 weeks. The endpoint therefore concerns both whether an ulcer occurrence was recorded and when it was first recorded during follow-up.

Time-to-event outcomes are useful when the timing of an event matters and participants may have different follow-up durations. In general, such analyses can use information about event timing while accounting for participants who have not experienced the event by the end of their observed follow-up. This is a general explanation, not a description of a statistical method confirmed for this trial.

The posted primary outcome information gives 24 participants with an occurrence by the 48-week assessment among 364 participants in the interim efficacy evaluation. It does not provide treatment-group counts, event-time distributions, a hazard ratio, a survival estimate, a confidence interval, or a test result. Consequently, the stated endpoint can be described, but the registry record does not allow a numerical comparison between the randomized groups or an assessment of the precision of such a comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Random assignment is intended to make treatment groups comparable at the start of a study, on average, including with respect to both measured and unmeasured participant characteristics. This supports an interpretation of between-group differences as treatment comparisons, provided the analysis and follow-up preserve the randomized comparison. The registry identifies the study as randomized but does not describe the sequence-generation procedure, allocation concealment, or the precise analysis population used for the primary outcome. Those details are not reported in the registry record.

What does masking mean?

The registry describes the trial as double-blind in its official title and identifies masking as quadruple. Masking is intended to reduce the chance that knowledge of assigned treatment influences care, outcome assessment, or reporting. The record does not identify which participant or study roles were included in the quadruple masking description, or describe how masking was maintained. It is therefore appropriate to report the stated masking without inferring the operational details.

How should the primary outcome be understood?

The outcome is framed as time from randomization to the occurrence of gastric and/or duodenal ulcers. In general, time-to-event analyses distinguish the timing of events from a simple total count. They may also account for participants whose event has not been observed by the end of follow-up, often called censoring. This is general statistical context; the registry record does not state which time-to-event estimator or model was used here, or whether censoring was handled in a particular way.

The registry describes ulcer assessments every 12 weeks through 48 weeks and reports 24 participants with an occurrence by the 48-week assessment among 364 in the interim efficacy evaluation. This count does not by itself reconstruct the time-to-event analysis. The record does not provide group-specific event counts, event times, risk sets at each assessment, or a comparative time-to-event estimate. A reader should not infer these missing results from the overall count.

Why does uncertainty matter?

A confidence interval is a range of values compatible with the observed data under a specified statistical model and procedure. It communicates the precision of an estimate: a narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. A p-value, when reported, describes how incompatible the data are with a specified null hypothesis under the analysis assumptions; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.

What is over-dispersion, in general?

Over-dispersion occurs when count data vary more than would be expected under a model that assumes a particular mean-variance relationship. If it is present and ignored, standard errors and confidence intervals can be too small, and tests can be overly optimistic. This is general context for count outcomes. The registry does not report an over-dispersion assessment or identify a count model for this primary outcome. Moreover, the stated primary endpoint concerns time to ulcer occurrence, so a count-model explanation should not be mistaken for the method used in this trial.

How should planning illustrations be read?

Sample-size illustrations based on an observed effect are planning exercises, not results from the trial and not observed power. The stated assumptions for such an illustration are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the illustration concerns a total number of events; for other outcomes, it concerns participants per arm. These assumptions do not establish that the original trial was designed using them. The registry record does not report the trial’s own sample-size justification or planned power calculation.

What can be concluded from the posted analysis information?

The registry lists one analysis, but does not describe the analysis model, covariates, test procedure, handling of repeated assessments, interim-analysis boundaries, or adjustment for multiple comparisons. The primary outcome description explicitly refers to a data cut-off date for interim analysis, but the record does not state the interim-analysis plan or decision rules. A statistical method cannot be inferred from the design label or endpoint wording alone. The most defensible reading is therefore descriptive: the record reports an interim efficacy population and an overall ulcer occurrence count, but not the comparative estimate needed to evaluate the primary question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists ten outcome measures, including the primary ulcer outcome and secondary measures of gastric mucosal lesions, reflux esophagitis, and symptoms. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase if each is tested separately without adjustment. Statistical approaches to multiplicity can control that risk, but the appropriate approach depends on the protocol and the intended hierarchy of questions. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or which outcomes were treated as confirmatory.

The primary outcome description refers to analysis at a data cut-off for an interim analysis. Interim looks at accumulating data can require prespecified statistical safeguards to preserve the intended error rate. The record does not report the timing or number of planned interim analyses, stopping rules, or any adjustment associated with interim monitoring. No such plan should be inferred solely from the mention of an interim analysis.

The record states that participants not taking investigational drug were excluded from the interim efficacy evaluation, which included 364 participants. It does not describe an intention-to-treat analysis, a per-protocol analysis, the handling of participants who discontinued treatment, or methods for missing outcome data. The number and reasons for missing outcome observations are not reported in the registry record. These omissions matter because excluding participants or handling incomplete follow-up differently can affect the interpretation of a randomized comparison.

The registry gives a total number of ulcer occurrences by the 48-week assessment but not treatment-specific counts or a description of how missing assessments were treated. It also does not describe sensitivity analyses. Without those details, the robustness of the primary outcome comparison cannot be assessed from 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (0.9%), brain stem haemorrhage (0.9%), dehydration (0.5%), hip fracture (0.5%), infective exacerbation of chronic obstructive airways disease (0.5%).

The registry reports serious adverse events for each treatment group using an at-risk group size and a count of participants affected. In the esomeprazole group, 17 of 214 participants were affected; in the placebo group, 15 of 213 were affected. For other adverse events, the reported affected counts are 70 of 214 and 53 of 213, respectively. These figures describe counts in the posted safety record, not a formal test of a treatment-group difference.

The listed serious adverse event terms include Acute Myocardial Infarction and Brain Stem Haemorrhage, each reported as 0.9%, and Dehydration, Hip Fracture, Infective Exacerbation Of Chronic Obstructive Airways Disease, and Pneumonia, each reported as 0.5%. These percentages are reproduced as recorded; the registry excerpt does not explain their calculation or give term-specific group breakdowns. The terms should not be read as exhaustive lists of all serious events.

Serious adverse events and other adverse events are separate categories in the record, and the reported counts do not indicate whether participants experienced more than one event. Death counts are not reported in the registry record. No adjustment, uncertainty interval, or comparative safety test is reported, so these figures should be interpreted descriptively rather than as evidence of a treatment effect.

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

The record establishes that a Phase III randomized study compared esomeprazole 20 mg once daily with placebo in people with a history of gastric and/or duodenal ulcers who were using continuous low-dose aspirin. It also describes follow-up for ulcer occurrence through a maximum of 48 weeks at the interim analysis, with assessments every 12 weeks. These design details clarify the clinical question and the period over which the primary outcome was assessed.

The posted interim efficacy information identifies 364 participants in the efficacy evaluation and reports 24 participants with ulcer occurrence by the 48-week assessment. That overall count does not identify how many occurrences were in either randomized group. It therefore cannot show whether one group had fewer or later events, quantify an effect, or establish the precision of a treatment comparison. No primary outcome confidence interval, p-value, or group-specific estimate is reported in the registry record.

The safety record reports affected-participant counts for serious and other adverse events in both groups. Those descriptive counts do not, on their own, establish that the groups differ, and they do not provide information about the severity or timing of every event beyond the categories and terms listed. The record does not report death counts.

These limitations concern what can be learned from the registry record, not what may be available in other sources. The absence of comparative primary outcome results in this record does not mean the trial found no difference, nor does it mean that a difference was found. It means that the posted information does not permit a sound estimate of the relative ulcer outcome between esomeprazole and placebo. No conclusion about an individual’s care follows from these registry figures.

13. Why This Trial Matters Statistically

This trial raises a statistical question in which event occurrence and event timing both matter. A simple overall event count can indicate how many participants experienced an outcome during a stated period, while a time-to-event comparison can also use information about when events arose and how long participants were observed. The distinction is important: the primary endpoint is described in time-to-event terms, but the posted interim outcome information gives only an aggregate count by the 48-week assessment.

The record also illustrates why the analysis population must be read alongside enrollment. The study enrolled 427 participants, while 364 were included in the interim efficacy evaluation, and participants not taking investigational drug were excluded from that evaluation. Those numbers describe different populations. Interpreting a result requires knowing who was included, why others were excluded, and how incomplete follow-up was handled; those details are not fully.

Randomization and masking are important design features, but they do not replace transparent reporting of group-specific results, uncertainty, and analysis methods. For this question, the critical missing information is the distribution of ulcer occurrences between the randomized arms and the comparative time-to-event estimate. Without it, the registry supports a description of the study design but not a quantitative evaluation of the primary treatment comparison.

Finally, safety counts need the same care. Counts can summarize how many participants were affected, but interpretation also depends on event definitions, overlap among participants, follow-up, and comparative uncertainty. The registry supplies selected counts and terms without a reported safety comparison. This record is therefore a useful example of why outcome definitions and design labels must be distinguished from complete statistical results.

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 is described as time to ulcer occurrence, but the registry reports only an overall count by the 48-week assessment. It does not report arm-specific event counts, the timing of events, a time-to-event estimate, or its uncertainty. As a result, the central comparative question cannot be evaluated from the posted primary outcome information.

The efficacy evaluation included 364 participants, while enrollment was 427. Participants not taking investigational drug were excluded, but the record does not give a complete participant flow or reasons for other exclusions. It does not state how treatment discontinuation, incomplete follow-up, or missing ulcer assessments were handled. This limits assessment of the consequences of excluding participants from the efficacy analysis.

The primary outcome description refers to an interim analysis, but the record does not report the analysis plan, interim monitoring procedures, or decision rules. It also does not state the statistical model, covariates, or multiplicity procedures. The registry lists secondary outcomes, but their comparative results are not reported in the available record. The death field contains no reported count, and the safety information does not include comparative uncertainty or a formal analysis.

The registry’s title identifies D961H, while the intervention and arm descriptions identify esomeprazole 20 mg once daily. The record does not explain this naming difference, so the descriptions can be reported as listed without inferring additional formulation or treatment details. Taken together, these gaps limit independent assessment of the primary efficacy result, analysis robustness, and comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparative Efficacy & Safety Study of D961H Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With Low-dose Aspirin — NCT01069939.
• Registry record last updated 2012-11-22; status last verified 2012-10.
• Results first posted 2012-11-22.
• 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

This completed Phase III randomized, quadruple-masked, parallel-group study compared esomeprazole 20 mg once daily by mouth with placebo once daily by mouth in participants with a history of gastric and/or duodenal ulcers receiving continuous low-dose aspirin. The registry reports 427 participants enrolled and 364 included in the interim efficacy evaluation, excluding participants not taking investigational drug.

The primary outcome was time from randomization to gastric and/or duodenal ulcer occurrence, assessed every 12 weeks up to 48 weeks. The record reports 24 occurrences among the 364 efficacy participants by the 48-week assessment, but gives no arm-specific primary outcome results or comparative estimate. Serious adverse events affected 17 participants in the esomeprazole group and 15 in the placebo group; other adverse events affected 70 and 53, respectively. Comparative statistical results, analysis details, and death counts are not reported in the registry record.