Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers in High Risk Subjects Compared to Arthrotec: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers in High Risk Subjects Compared to Arthrotec (NCT00594854), a randomized phase 3 study. The primary outcome is Number of Participants With Gastric Ulcer Confirmed by Endoscopy.

2. Clinical Question

The study was registered as a phase 3, randomized, double-blind, parallel-group, controlled, multicenter trial. Its brief summary describes efficacy, tolerability, and safety as aims, while the registered primary outcome is specifically the number of participants with an endoscopically confirmed gastric ulcer. Two secondary outcomes are listed: duodenal ulcers confirmed by endoscopy and upper gastrointestinal injury grade 4 measured by the Lanza (1991) score. Their names are registered, but secondary outcome results are not reported in the registry record.

3. Trial Design

The registry record describes a randomized, double-blind, parallel-group, controlled phase 3 study comparing PN400 (VIMOVO) with Arthrotec. Its official title identifies a 6-month study of gastric ulcer incidence in people at high risk for developing NSAID-associated ulcers. The brief summary describes the study as multicenter and says approximately 100 sites were expected to participate. The record does not report how randomization was generated, how allocation was concealed, or how masking was maintained.

The planned enrollment was 200 participants, with 100 per arm. The registry record reports actual enrollment of 20: 9 in the PN400 arm and 11 in the Arthrotec arm. It also states that at least 20% of participants enrolled were intended to be age 65 years and older, but the age distribution among those enrolled is not reported in the registry record. The planned site count and enrollment are design intentions; they should not be confused with the smaller recorded enrollment.

The study status is terminated. The record lists a start of 2007-09 and a primary completion of 2008-09. The reason for termination is not reported in the registry record. It also does not explain whether the 20 participants completed the intended follow-up or whether all participants contributed to the primary outcome assessment.

The primary outcome was the number of participants with a gastric ulcer confirmed by endoscopy over 6 months. The record lists two secondary outcomes, but does not report their results. Although the outcome counts are posted for both arms, the record contains no analysis for a two-arm binary comparison; it explicitly notes that values were missing or not estimable for such a comparison. Thus the available outcome information is descriptive rather than a reported comparative analysis.

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: Screening for eligibility and wash-out of restricted medications.

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 Number of Participants With Gastric Ulcer Confirmed by Endoscopy, measured over 6 months.

The primary endpoint counts participants with a gastric ulcer confirmed by endoscopy after administration of PN400 or Arthrotec over the 6-month timeframe. It is a binary participant-level outcome in the sense that each participant is classified according to whether an ulcer was confirmed, while the posted arm result is the count of participants meeting that definition. The registry record labels the unit as participants and describes the endpoint as a number, not as a continuous measurement or a time-to-event estimate.

Endoscopic confirmation gives the registered outcome a stated assessment method: the ulcer is identified by endoscopy rather than being defined only by symptoms. In general, a defined and consistently applied outcome assessment can help make comparisons interpretable. The registry record does not report the detailed endoscopy procedures, assessment schedule, reading process, or criteria used to confirm an ulcer, so those aspects cannot be evaluated from the record.

The outcome is used to address the study's stated question about gastric ulcers in a high-risk population receiving the compared regimens. The endpoint is distinct from the listed secondary outcomes, which concern duodenal ulcers and upper gastrointestinal injury grade 4. Results for those secondary measures are not reported in the registry record. The primary endpoint counts are 2 participants in the PN400 arm and 1 in the Arthrotec arm; without a reported comparative estimate and uncertainty measure, these counts describe the observed participants but do not quantify a precise difference between the regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary endpoint is a participant count for an event that can be present or absent: a gastric ulcer confirmed by endoscopy. The registry record gives counts and arm sizes, but does not report a comparative statistical analysis. The distinction matters. Descriptive counts tell the reader what was recorded among enrolled participants; an inferential comparison estimates how compatible the observed data are with a range of possible differences between groups, under stated assumptions.

What does an effect estimate add to event counts?

In general, an effect estimate expresses the contrast between groups using a defined measure, such as a difference in event proportions or a relative measure. A confidence interval gives a range of values compatible with the data and the analysis assumptions, and communicates uncertainty as well as direction. A narrow interval indicates greater precision than a wide interval. Neither an estimate nor its interval establishes causation by itself; interpretation also depends on study conduct, endpoint definition, and the analysis plan. The registry record does not report an effect estimate or confidence interval for this endpoint.

The record specifically says that a two-arm comparison for the binary endpoint was missing or not estimable. It would therefore be inappropriate to attach a significance conclusion or a precision claim to the arm counts. Although a reader can see that the posted counts are 2 in one arm and 1 in the other, deriving a new contrast or uncertainty interval would require calculation and choices about methods that are not reported as the sponsor's analysis. No sponsor analysis is available in the registry record to take precedence over a recalculation.

Why can a small event count be difficult to interpret?

In general, when an outcome is uncommon in the observed data and the groups are small, a limited change in the recorded events can have a substantial influence on a comparative estimate. Estimates may be imprecise, and methods that rely on large-sample approximations may not perform well in sparse data. Alternative methods can be considered in statistical practice, but the registry record does not identify a method used for this endpoint, and no alternative result should be assumed. The key point is that the event counts do not by themselves reveal the uncertainty around a treatment contrast.

Likewise, the absence of a reported comparison is not evidence that the treatments are equivalent. Equivalence or non-inferiority requires a defined margin and a planned analysis that evaluates whether uncertainty excludes differences beyond that margin. Such a margin and analysis are not reported in the registry record. A lack of a reported statistically significant result would also not be interpretable here, because the record does not report a test result at all.

How should enrollment and planning assumptions be read?

The registry record states a planned enrollment of 200 participants, with 100 per arm, while reporting actual enrollment of 20. The planned figures describe the intended design, not the enrolled population analyzed in the posted results. A planned sample size can be selected to achieve a target level of precision or power under assumptions about the outcome and treatment effect. The registry record does not report its own sample-size justification, the assumptions used for that design, or a target power for the original trial.

Any separate sample-size planning illustration based on an observed effect is not the trial's original design justification and is not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the detectable effect defined as a stated fraction of the observed effect. General planning calculations estimate the sample size that would be needed under specified assumptions; they do not change the number enrolled, recover missing outcomes, or show that a study had a particular probability of detecting an effect after results are known. No particular planning result should be inferred from assumptions alone.

What does randomization contribute?

In general, random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics at assignment. This supports a causal interpretation when the trial is conducted and analyzed as planned. Randomization does not guarantee balance in a small sample, and it does not correct problems arising from missing outcomes, departures from assigned treatment, or selective analysis. The record identifies the study as randomized but does not report the sequence-generation method, allocation concealment, adherence, or crossovers.

Double masking is also listed. In general, masking can reduce the risk that expectations affect care, outcome assessment, or reporting, depending on who was masked and how the masking was maintained. The registry record does not specify which parties were masked or describe masking procedures. Endoscopic confirmation gives the endpoint a stated assessment modality, but the record does not explain whether endoscopy readers were masked to assignment.

Finally, the analysis should be understood as a record-level description rather than a complete statistical report. The registry record does not report an analysis population, a missing-data procedure, a model, an adjustment strategy, or interim analyses. Those omissions limit evaluation of the intended estimand and of how the observed counts were obtained. General statistical principles can explain what such methods would address, but they cannot fill in undocumented choices for this trial.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("PN400 (VIMOVO)", "Arthrotec")
n      <- c(9, 11)
events <- c(2, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  PN400 (VIMOVO)  9  2  22.2  2.8  60.0  6.3  54.7  6.7  55.6
ARM  Arthrotec  11  1  9.1  0.2  41.3  1.6  37.7  2.1  38.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and two secondary outcomes. The primary outcome is the count of participants with gastric ulcers confirmed by endoscopy. The secondary outcomes concern duodenal ulcers confirmed by endoscopy and upper gastrointestinal injury grade 4 measured by the Lanza (1991) score. Their results are not reported in the registry record.

Multiplicity arises when several outcomes or multiple statistical tests are used to draw conclusions. In general, conducting many tests can increase the chance of at least one apparently notable result, so a prespecified approach may define which outcomes are confirmatory and whether adjustments are needed. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or an analysis plan. Because secondary results and analyses are not posted, their relationship to any primary inference cannot be assessed.

The record does not report how missing endpoint data were handled, whether every enrolled participant underwent endoscopy, or whether any participants were excluded from the outcome counts. It also does not define an intention-to-treat, per-protocol, or other analysis population. In general, missing outcomes can affect both the effective information in a study and the interpretation of group comparisons; the direction of any effect depends on why data are missing and how they are handled. No missing-data assumptions can be attributed to this trial from the available record.

The enrollment of 20 and the posted arm counts do not establish that all participants completed follow-up or were analyzed under a particular population definition. The status is terminated, but the record does not describe the analysis consequences of termination. These gaps make it difficult to determine whether the endpoint counts represent all randomized participants, participants with observed endoscopy, or another population.

12. 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 non-serious adverse event terms

The registry record reports 0 serious adverse events among 9 participants in the PN400 arm and 0 among 11 participants in the Arthrotec arm. It also reports other adverse events for 7 of 9 participants in the PN400 arm and 8 of 11 in the Arthrotec arm. These figures describe the participants recorded in each group; they are not adjusted comparative estimates.

A zero serious-event count means that no serious adverse events were recorded in the listed group during the registry's reporting, not that the possibility of such events has been ruled out. With a small number of participants, the counts provide limited information about less common events. In general, an uncertainty interval would help convey how imprecise an event-rate estimate may be, but the registry record does not report safety intervals or a formal between-group analysis.

The record does not provide the definitions, event-level descriptions, severity details, timing, or relatedness assessments for the serious adverse events. It lists no serious-event terms, and death values are not reported in the registry record. The “other” adverse-event counts should not be interpreted as a complete account of event types or severity without further detail. These data support only a cautious descriptive reading of what was recorded, not a comparative safety conclusion.

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

The posted primary outcome results show 2 participants with an endoscopically confirmed gastric ulcer in the PN400 arm and 1 in the Arthrotec arm. The recorded arm sizes were 9 and 11, respectively. These observations answer a narrow descriptive question about the participants included in the registry results. They do not provide an estimate of the treatment contrast with a measure of its precision.

The missing comparative analysis is important to interpretation. The registry record says that values were missing or not estimable for a two-arm comparison of the binary endpoint. There is no reported confidence interval, test result, or model-based estimate. The counts therefore cannot establish that one regimen had a higher or lower underlying ulcer risk, and they cannot establish equivalence. Nor does the absence of an estimable comparison show that no treatment difference exists.

The trial was intended to enroll 200 participants, but the record reports enrollment of 20 and a terminated status. This limits the extent to which the posted observations can represent the intended study. The reason for termination, completion of follow-up, and the analysis population are not reported in the registry record. Without those details, it is not possible to determine why the study ended or how completely the registered outcome was assessed.

The record also does not report results for the two secondary outcomes. Safety counts are available, but they are descriptive and do not include a comparative analysis or enough detail to assess event types and uncertainty. Thus the record is useful for identifying the study question, design, enrollment, and the small set of posted outcomes, while leaving major elements of the intended statistical interpretation unresolved.

In general, a treatment effect is best interpreted with its design context, analysis population, endpoint procedures, and uncertainty. Those elements help distinguish a noisy observed contrast from a precise, reproducible finding. Here, the registry record does not provide the comparative analysis needed for that assessment. The appropriate conclusion is limited to the counts and the limitations of the reported information; no medical recommendation or efficacy conclusion follows from these counts alone.

14. Why This Trial Matters Statistically

This trial illustrates why a registry entry's design intentions and posted results need to be distinguished. The planned enrollment was 200 participants, with 100 per arm, while the recorded enrollment was 20. The study is listed as terminated. Those details establish that the posted results come from a substantially smaller enrollment than the intended design, but do not explain why enrollment was limited or why the study ended.

It also illustrates the distinction between descriptive outcome counts and an inferential comparison. The primary outcome is clinically framed as an endoscopically confirmed gastric ulcer, and the registry provides counts in both groups. Yet it does not report an estimable two-arm analysis. Without a comparative estimate and uncertainty measure, the numerical contrast cannot be translated into a precise statement about the treatment difference.

The registry's specificity varies across design elements. It identifies randomization, double masking, a parallel-group model, and a 6-month timeframe, but does not report the sequence-generation process, masking procedures, detailed outcome assessment methods, analysis populations, missing-data handling, or the statistical analysis plan. This shows how a record can identify the broad trial structure while leaving important information for assessing bias and statistical validity unavailable.

The trial also names secondary outcomes and records adverse-event counts, but does not provide their inferential analyses or detailed event descriptions. Statistical interpretation is not limited to the primary result: endpoint hierarchy, multiplicity, missing data, and safety reporting can all affect what conclusions are supported. In this record, those considerations remain largely undocumented.

For clinical researchers and biostatisticians, the central lesson is one of calibrated inference. The observed counts are real features of the posted record, but sparse data and absent analysis details sharply constrain what can be concluded. A transparent account of the planned estimand, outcome ascertainment, participant flow, and analysis would be necessary to evaluate the intended comparison fully.

15. 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 specific to this trial record is the difference between intended and reported enrollment: the registry describes a planned total of 200 participants and reports actual enrollment of 20. The record lists the study as terminated, but the reason for termination is not reported in the registry record. It is therefore not possible to attribute the enrollment or status to any particular cause.

The primary outcome counts are sparse, and the record states that a two-arm binary comparison was missing or not estimable. No comparative effect estimate, confidence interval, or test result is reported. The counts alone do not provide a basis for judging the precision of the treatment contrast. The registry also does not state whether all randomized participants had endpoint assessment or define the population underlying the counts.

Important design and conduct details are not reported in the registry record. These include the randomization method, allocation concealment, who was masked, endoscopy procedures and review, adherence, treatment discontinuation, and any crossovers. The record does not describe participant flow or explain whether the planned age criterion was achieved; it only states the intended minimum proportion aged 65 years and older.

The analysis plan, missing-data approach, multiplicity strategy, and analysis populations are not reported. The two secondary outcomes are listed without results. The safety record gives aggregate counts but does not report event-level descriptions, death values, or comparative uncertainty. These omissions restrict assessment of both efficacy-related outcomes and safety, and they preclude conclusions beyond the limited descriptive information posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers in High Risk Subjects Compared to Arthrotec — NCT00594854.
• Registry record last updated 2010-09-22; status last verified 2010-08.
• Results first posted 2010-09-22.
• 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.

19. Record Summary

The registry record identifies NCT00594854 as a phase 3, randomized, double-blind, parallel-group study of PN400 (VIMOVO) versus Arthrotec in people at high risk for NSAID-associated gastric ulcers. The intended study duration was 6 months, with planned enrollment of 200 participants. The record reports enrollment of 20 and a terminated status, with a start of 2007-09 and primary completion of 2008-09.

The primary endpoint was the number of participants with gastric ulcers confirmed by endoscopy. The posted counts are 2 among 9 participants in the PN400 arm and 1 among 11 in the Arthrotec arm. A two-arm comparison was not estimable in the record, and no comparative estimate or uncertainty measure is reported. Two secondary outcomes are listed without results. Serious adverse-event counts are 0 in each arm; other adverse-event counts are 7 of 9 and 8 of 11. The reason for termination and key analysis details are not reported in the registry record.