Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Helicobacter Pylori Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Helicobacter Pylori Infection (NCT04167670), a randomized phase 3 study. The primary outcome is Percentage of Participants With Successful Helicobacter Pylori (H Pylori) Eradication in Participants Without a Clarithromycin- or Amoxicillin-resistant Strain of H Pylori at Baseline.

2. Clinical Question

3. Trial Design

The registry record describes a completed, randomized, parallel-group phase 3 study sponsored by Phathom Pharmaceuticals, Inc. Enrollment was 1046. The recorded study start was 2019-12-10 and primary completion was 2021-03-10. Helicobacter pylori infection was the condition under study.

Three regimens were compared: vonoprazan dual therapy, vonoprazan triple therapy, and lansoprazole triple therapy. Each regimen was specified for 14 days. The official title describes the dual-therapy regimen as open-label and the triple-therapy regimens as double-blind, while the registry’s masking designation is quadruple. The relationship between those descriptions is not explained in the registry record.

The primary endpoint was assessed from baseline to 4 weeks after the last dose of study drugs; the maximum treatment duration was 2 weeks. The primary efficacy population was a modified intent-to-treat population, limited to randomized participants with baseline infection documented by ¹³C-UBT and biopsy and without a clarithromycin- or amoxicillin-resistant strain. Thus, the primary result applies to that defined population rather than automatically to every participant enrolled.

The record lists three outcome measures and six analyses. It reports the primary outcome and two secondary outcomes: eradication among participants with clarithromycin-resistant infection at baseline, and eradication among all participants. The original sample-size justification, allocation ratio, and detailed protocol for analysis are not reported in the registry record.

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: A \^13C-urea breath test (\^13C-UBT) was performed within 34 days prior to treatment to establish Helicobacter pylori (H pylori) infection status. 6 gastric mucosal biopsy specimens were collected to determine resistance of bacteria to clarithromycin, amoxicillin, and metronidazole antibiotics and to document H pylori infection. 3385 participants were screened, 2339 of which were screen failures. 1046 participants were randomized and 1039 received at least 1 dose of the study drugs.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat Primary (MITTp) Analysis Set - All participants randomized into the study who had a H pylori infection documented by \^13C-UBT and biopsy (ie, culture or histology) at baseline and did not have a clarithromycin- or amoxicillin-resistant strain of H pylori at baseline.

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.

Population: Randomized Set - All participants randomly assigned to receive study drug regardless of whether or not they received a dose of study drug during the study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Successful Helicobacter Pylori (H Pylori) Eradication in Participants Without a Clarithromycin- or Amoxicillin-resistant Strain of H Pylori at Baseline, measured over Baseline to 4 weeks after the last dose of study drugs (maximum duration of treatment was 2 weeks).

The primary endpoint is the percentage of participants with successful H pylori eradication. Eradication was determined using the ¹³C-UBT test, with the assessment window extending from baseline to 4 weeks after the last dose of study drugs. The maximum duration of treatment was 2 weeks.

This endpoint captures whether infection was successfully eradicated by the specified follow-up assessment. Reporting it as a percentage makes the outcome interpretable as the proportion of participants in each regimen group who met the eradication definition. The posted primary results are 78.5% for vonoprazan dual therapy, 84.7% for vonoprazan triple therapy, and 78.8% for lansoprazole triple therapy.

The endpoint’s population definition is important to its interpretation. The primary analysis included randomized participants with H pylori infection documented by ¹³C-UBT and biopsy at baseline and excluded those with a clarithromycin- or amoxicillin-resistant strain at baseline. Results for clarithromycin-resistant infection and for all participants were reported separately as secondary outcomes. The primary endpoint therefore addresses eradication in a specifically selected baseline population, rather than providing a single result for all resistance profiles.

The registry record does not report further detail on how missing or unevaluable ¹³C-UBT results were handled. That limits assessment of how the measured percentage would be affected if some participants lacked an evaluable follow-up test.

7. Results Posted in the Registry

• Vonoprazan Triple Therapy: 84.7% (222/262) versus 78.5% (208/265) on control; risk difference 6.2 percentage points (95% CI -0.3 to 12.8), risk ratio 1.08 (1.00–1.17); unadjusted two-proportion z-test p = 0.064.
• Lansoprazole Triple Therapy: 78.8% (201/255) versus 78.5% (208/265) on control; risk difference 0.3 percentage points (95% CI -6.7 to 7.4), risk ratio 1.00 (0.92–1.10); unadjusted two-proportion z-test p = 0.926.

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.

Percentage of Participants With Successful Helicobacter Pylori (H Pylori) Eradication in Participants With a Clarithromycin-resistant Strain of H Pylori at Baseline

• 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:
  • Vonoprazan Triple Therapy: 65.8% (48/73) versus 69.6% (39/56) on control; risk difference -3.9 percentage points (95% CI -20.1 to 12.3), risk ratio 0.94 (0.74–1.20); unadjusted two-proportion z-test p = 0.640.
  • Lansoprazole Triple Therapy: 31.9% (23/72) versus 69.6% (39/56) on control; risk difference -37.7 percentage points (95% CI -53.9 to -21.5), risk ratio 0.46 (0.31–0.67); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vonoprazan Triple Therapy and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Lansoprazole Triple Therapy than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of All Participants With Successful Helicobacter Pylori (H Pylori) Eradication

• 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:
  • Vonoprazan Triple Therapy: 80.8% (273/338) versus 77.2% (250/324) on control; risk difference 3.6 percentage points (95% CI -2.6 to 9.8), risk ratio 1.05 (0.97–1.13); unadjusted two-proportion z-test p = 0.254.
  • Lansoprazole Triple Therapy: 68.5% (226/330) versus 77.2% (250/324) on control; risk difference -8.7 percentage points (95% CI -15.5 to -1.9), risk ratio 0.89 (0.81–0.98); unadjusted two-proportion z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vonoprazan Triple Therapy and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Lansoprazole Triple Therapy than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the view beyond the primary population: one concerns participants with clarithromycin-resistant infection at baseline, and the other concerns all participants. The posted results show a different pattern across these populations than a simple extension of the primary result. That distinction matters because the secondary analyses do not have the same population definition as the primary analysis.

The resistant-infection outcome is particularly relevant as a subgroup result, but subgroup findings can be less stable and should not be treated as interchangeable with the primary analysis. The all-participant outcome gives a wider population view, though it combines participants with differing baseline resistance status. Neither outcome answers exactly the same question as the primary endpoint, which excluded participants with either clarithromycin- or amoxicillin-resistant infection.

General statistical explanation: an apparent difference between subgroup outcomes does not establish that a treatment effect varies by subgroup. That requires a formal assessment of interaction, and such an analysis is not reported in the registry record. Nor does a significant result in one population and a non-significant result in another, by itself, prove that the effects differ.

The registry record lists six analyses across the primary and secondary outcomes, but does not report a multiplicity adjustment for the secondary results. When multiple comparisons are considered, unadjusted p-values carry less weight because chance findings become more likely across a set of tests. Secondary results are best read as supporting context and as estimates that may inform further study, rather than as independent confirmation of the primary conclusion.

The varying analysis populations and the lack of reported multiplicity procedures, interaction testing, and detailed missing-data methods limit how strongly the secondary results can be interpreted. Their role is to complement, not displace, the prespecified primary endpoint and the sponsor’s reported primary analysis.

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

• Percentage of Participants With Successful Helicobacter Pylori (H Pylori) Eradication in Participants With a Clarithromycin-resistant Strain of H Pylori at Baseline
• Percentage of All Participants With Successful Helicobacter Pylori (H Pylori) Eradication

9. Statistical Interpretation

10. Statistical Methods Explained

Comparing percentages. The primary outcome is binary: each participant either met the eradication definition or did not. A group percentage expresses the frequency of successful eradication among the participants included in that group’s analysis. General statistical explanation: a risk difference subtracts one group’s event proportion from the other’s. Its sign depends on the comparison order; a positive value in these recalculations means the named comparison group had a higher observed eradication proportion than the vonoprazan dual therapy reference group.

The recalculated comparisons use posted group summaries and are unadjusted. For vonoprazan triple therapy versus vonoprazan dual therapy, the estimated risk difference is 0.062, with a 95% confidence interval from -0.004 to 0.128 and p = 0.064. For lansoprazole triple therapy versus vonoprazan dual therapy, the estimated difference is 0.003, with a 95% confidence interval from -0.067 to 0.074 and p = 0.926. These recalculations do not replace the sponsor’s analysis.

Non-inferiority analysis. General statistical explanation: a non-inferiority analysis asks whether a treatment’s outcome is not worse than a comparator by more than a prespecified margin. This differs from asking whether the groups have exactly the same outcomes, and it also differs from a conventional test of any difference. The margin is central to judging the result. The registry record reports Farrington and Manning tests and labels the primary comparisons non-inferiority, but the non-inferiority margin is not reported in the registry record. The sponsor’s reported analyses therefore take precedence over simple recalculations, while the absent margin limits independent interpretation of the non-inferiority claim.

The sponsor reported a percentage difference of -0.3 for vonoprazan dual therapy compared with lansoprazole triple therapy, with a 95% confidence interval from -7.39 to 6.76 and p = 0.004. For vonoprazan triple therapy compared with lansoprazole triple therapy, the reported difference was 5.9, with a 95% confidence interval from -0.75 to 12.62 and p < 0.001. These p-values belong to the reported non-inferiority analyses; they should not be read as ordinary tests showing that the groups differ or as measures of the size of an effect.

Confidence intervals and p-values. General statistical explanation: a confidence interval describes a range of values compatible with the data and the statistical procedure under its assumptions. It communicates uncertainty about the estimated effect, not the probability that a particular effect is true. For a risk difference, an interval spanning zero includes no difference among the values compatible with that interval. A p-value describes how unusual the data would be under a specified null hypothesis and model; it does not quantify clinical importance or the probability that the null hypothesis is true.

The recalculated intervals are not the same as the sponsor’s reported intervals. This discrepancy is explicitly recorded, so the recalculations should be treated as descriptive cross-checks rather than as an alternative primary analysis. Differences in analysis specifications can lead to different estimates or tests, but the registry record does not provide enough information to identify the reason for the discrepancy.

Analysis populations and subgroup outcomes. The primary result concerns a modified intent-to-treat population defined by baseline infection tests and absence of either specified resistance. The secondary clarithromycin-resistant analysis addresses a different population, and the all-participant analysis has another denominator. General statistical explanation: results from separate populations can differ because the populations and their baseline characteristics differ; comparing their percentages does not by itself establish that resistance caused a difference in treatment effect. The registry record does not report a formal interaction analysis.

Six analyses are listed across the primary and secondary outcomes. The registry record does not report how multiplicity across those analyses was addressed. In general, multiple tests can increase the chance of at least one apparently notable result when each is considered without adjustment. This is why secondary p-values, especially when described as unadjusted, warrant more caution than a prespecified primary analysis.

Further details of the statistical plan, including missing-data procedures, sensitivity analyses, and any interim analyses, are not reported in the registry record. These omissions constrain independent evaluation of how robust the reported estimates are to choices made in the analysis.

11. Confidence Intervals and Precision

The primary recalculated risk-difference intervals are broad enough to include both no difference and potentially meaningful differences in either direction. For vonoprazan triple therapy versus vonoprazan dual therapy, the estimate is 0.062 and the 95% confidence interval ranges from -0.004 to 0.128. For lansoprazole triple therapy versus vonoprazan dual therapy, the estimate is 0.003 and the interval ranges from -0.067 to 0.074. These intervals do not pin down a single precise difference.

General statistical explanation: a confidence interval represents uncertainty in an estimate under the statistical method used. It is not a guarantee that the true value lies inside the interval, and it does not assign probabilities to individual values. When an interval includes zero for a difference, the data are compatible with no difference as well as with values on either side of zero. The interval’s width is therefore important alongside its central estimate.

The sponsor’s reported intervals use a different analysis and are associated with non-inferiority tests. The registry record reports intervals from -7.39 to 6.76 for the dual-therapy comparison and from -0.75 to 12.62 for the triple-therapy comparison. Since the non-inferiority margin is not reported in the registry record, the ranges cannot by themselves establish whether the sponsor’s margin-based criterion is satisfied. The discrepancy flag means the sponsor’s analysis takes precedence over the recalculated comparison.

The secondary outcomes also have uncertainty, and the resistant subgroup is analyzed in a different population from the primary endpoint. Those estimates should not be treated as equally precise or directly interchangeable with the primary result. The posted group percentages are useful descriptions, but precision requires considering the corresponding interval and the analysis population. The registry record does not report confidence intervals for the group percentages themselves.

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 estimates are participants per arm, not total participants, because the stated illustration assumes equal allocation between two arms. The calculation uses a two-sided significance level of 0.05 and a normal approximation. It uses the observed effect as its starting point and considers planning for 100%, 75%, or 50% of that observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and those assumptions were correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are prospective planning quantities; they are not the probability that the completed trial found a true effect.

For example, the primary comparison of vonoprazan triple therapy with vonoprazan dual therapy lists 604 participants per arm for 80% power and 808 participants per arm for 90% power when planning for 100% of the observed effect. Planning for 75% of that effect lists 1,109 and 1,484 participants per arm, respectively; planning for 50% lists 2,573 and 3,443. The figures demonstrate the general pattern: smaller effects require more participants to detect, all else being equal.

These are planning illustrations computed from the observed effect, not the trial’s original design calculation. This is not observed power. A planning curve, if consulted, should be read as showing how the illustrative participant requirement changes with the effect assumption, not as a new result about the trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.785; treatment proportion p₁ = 0.847; average p̄ = 0.816.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5479 = 1.0738.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5461 = 0.4596.
4. n = (1.0738 + 0.4596)² / (0.0624)² = 603.4, rounded up to 604 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.784905660377359                          # control proportion
p1 <- 0.847328244274809                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4167670)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 604 (80% power), 808 (90% power)
 75% of observed effect: n per arm = 1,109 (80% power), 1,484 (90% power)
 50% of observed effect: n per arm = 2,573 (80% power), 3,443 (90% power)
power.prop.test: 603.4 
Simulated power at n = 604 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary analyses use Farrington and Manning tests and are labelled non-inferiority. The registry record reports a percentage difference of -0.3, with a 95% confidence interval from -7.39 to 6.76 and p = 0.004 for vonoprazan dual therapy compared with lansoprazole triple therapy. For vonoprazan triple therapy compared with lansoprazole triple therapy, it reports 5.9, with a 95% confidence interval from -0.75 to 12.62 and p < 0.001.

The recalculated primary comparisons are simple unadjusted calculations from posted summary statistics. They yield risk differences of 0.003 for lansoprazole triple therapy versus vonoprazan dual therapy and 0.062 for vonoprazan triple therapy versus vonoprazan dual therapy, with respective p-values of 0.926 and 0.064. The registry record flags a discrepancy between these recalculations and the sponsor analysis. The sponsor’s own analysis takes precedence.

The two sets of results should not be combined as if they came from one method. The sponsor’s analyses are framed around non-inferiority, while the recalculations are unadjusted comparisons of posted percentages. The non-inferiority margin and sufficient details to reconcile the methods are not reported in the registry record. Therefore, the sponsor analysis is the primary account of the registered inferential result, while the recalculation is a limited cross-check rather than a correction.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and two secondary outcomes, with six analyses listed overall. It reports sponsor analyses for the primary endpoint and secondary endpoints, including non-inferiority and superiority labels. However, a full statistical analysis plan is not reported in the registry record, so the ordering of hypotheses and the status of each test as prespecified or exploratory cannot be independently established from this record.

Multiplicity procedures are not reported in the registry record. General statistical explanation: when multiple hypotheses are tested, the chance of at least one low p-value arising by chance can increase. Adjustments or a prespecified testing hierarchy can address that issue, but no such procedure should be assumed. Consequently, unadjusted secondary results warrant particular caution and should not be interpreted as though each were the sole confirmatory test.

The primary population is described as a modified intent-to-treat analysis set: randomized participants with baseline H pylori infection documented by ¹³C-UBT and biopsy, without a clarithromycin- or amoxicillin-resistant strain at baseline. This definition is reported, but the registry record does not report how missing outcome tests, protocol deviations, or other exclusions were handled in that analysis.

The secondary outcome for clarithromycin-resistant infection has a separate subgroup population, while the all-participant outcome includes a broader group. Detailed analysis-population definitions for those secondary outcomes and the handling of missing data are not reported in the registry record. The group denominators differ across outcomes, so the percentages are based on outcome-specific analysis populations rather than one common denominator.

Interim analyses, stopping rules, imputation procedures, sensitivity analyses, and the original sample-size justification are not reported in the registry record. These omissions do not negate the posted results, but they limit independent assessment of potential missing-data effects, multiplicity, and the robustness of the inferential conclusions.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: pneumonia viral (0.3%), cholecystitis acute (0.3%), peripheral ischaemia (0.3%), cardiac arrest (0.3%), coronary artery occlusion (0.3%).

The registry record reports serious adverse events, other adverse events, and deaths separately for the three treatment groups. Serious adverse events were reported for 5 of 348 participants in the vonoprazan dual therapy group, 6 of 346 in the vonoprazan triple therapy group, and 3 of 345 in the lansoprazole triple therapy group. Other adverse events were reported for 20 of 348, 27 of 346, and 48 of 345, respectively. Deaths were reported as 0, 2, and 1, respectively.

These counts describe events in the recorded safety groups; they are not adjusted comparisons and do not establish that a treatment caused an event. The registry also lists serious adverse event terms with a reported frequency of 0.3%, including viral pneumonia, acute cholecystitis, peripheral ischaemia, cardiac arrest, coronary artery occlusion, and coronavirus infection. The record does not provide enough detail to assess timing, relatedness, or individual clinical circumstances. These figures should be interpreted as descriptive safety reporting, not as a complete comparative safety analysis.

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

The results describe observed H pylori eradication percentages under three regimens, assessed by ¹³C-UBT from baseline to 4 weeks after the last dose. The primary result is specifically about participants without clarithromycin- or amoxicillin-resistant infection at baseline. It does not directly answer the same question for participants with those resistance profiles; the registry reports separate secondary analyses for clarithromycin-resistant infection and for all participants.

The primary group percentages are close for vonoprazan dual therapy and lansoprazole triple therapy, and higher for vonoprazan triple therapy in the posted summaries. But the recalculated unadjusted confidence intervals include no difference, and the sponsor’s own primary analysis is the relevant reported inferential analysis because the registry record flags a discrepancy. That analysis is labelled non-inferiority. The non-inferiority margin is not reported in the registry record, so the strength and clinical interpretation of that claim cannot be independently assessed from the record alone.

These results do not prove that the regimens are identical, do not establish a result for every participant with H pylori infection, and do not show that an observed difference is caused by a particular component of a regimen. They also do not determine which regimen is appropriate for an individual. That would require clinical judgment beyond the statistical results.

The secondary outcomes add information about different analysis populations, but multiple analyses and unreported multiplicity procedures mean their unadjusted results should be interpreted cautiously. The safety figures are descriptive counts and do not establish comparative causation. Overall, the registry record provides outcome estimates and sponsor-reported tests, but incomplete information on margins, missing-data methods, and the detailed analysis plan limits how far the findings can be taken.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares distinct acid-suppression and antibiotic regimens using a binary eradication outcome, while distinguishing the primary population from resistance-defined and all-participant populations. That distinction makes clear that an efficacy estimate is tied to who was analyzed, not merely to the treatment label.

The record also illustrates why the estimand and test framework matter. A non-inferiority question is not the same as a conventional test for any difference. The sponsor reports Farrington and Manning non-inferiority analyses, whereas the posted-summary recalculations are unadjusted risk-difference comparisons. With a flagged discrepancy and an unreported non-inferiority margin, it is important to keep those analyses separate and avoid treating one as a direct validation of the other.

The secondary results highlight common interpretive challenges: subgroup outcomes may have different populations and precision, and multiple unadjusted tests can make isolated findings less persuasive. The record’s missing detail on multiplicity, missing data, and the full statistical plan also shows why registry results are most useful when considered alongside complete analysis documentation.

Finally, the sample-size illustrations demonstrate how planning requirements depend on the effect size chosen for detection. They are not evidence of the trial’s original design rationale or of observed power. Together, these features make the study a useful example of the need to read endpoint definitions, populations, confidence intervals, and sponsor analyses as a connected statistical account.

19. 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.

Several limitations are specific to the information reported for this trial. The primary analysis excludes participants with clarithromycin- or amoxicillin-resistant infection at baseline, so its result does not represent those excluded populations. The separate resistant-infection analysis concerns clarithromycin resistance, not a combined subgroup defined by both resistance types.

The sponsor’s primary analyses and the simple recalculations differ, and the registry record flags this discrepancy. The sponsor analysis takes precedence, but the registry record does not report the non-inferiority margin or enough details to reconcile the two approaches. This limits independent evaluation of the non-inferiority interpretation.

The record describes quadruple masking while the official title characterizes the dual therapy as open-label and the triple therapies as double-blind. It does not explain how those descriptions align. The original statistical analysis plan, allocation ratio, sample-size justification, missing-data procedures, sensitivity analyses, and interim analyses are not reported in the registry record.

There are multiple primary and secondary analyses, but multiplicity handling is not reported. The secondary populations differ, and formal interaction testing is not reported, limiting comparisons across population-specific results. The reported safety figures are descriptive; detailed event timing, relatedness, and comparative safety analyses are not posted in the registry record. These limitations affect interpretation of the posted record and do not, by themselves, establish that the trial was conducted improperly.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Helicobacter Pylori Infection — NCT04167670.
• Registry record last updated 2022-04-05; status last verified 2022-03.
• Results first posted 2022-04-05.
• 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.

23. Record Summary

NCT04167670 is a completed randomized phase 3 parallel-group study of vonoprazan dual therapy, vonoprazan triple therapy, and lansoprazole triple therapy for H pylori infection. The registry record lists enrollment of 1046 and reports primary eradication results for participants without clarithromycin- or amoxicillin-resistant infection at baseline. Eradication was determined by ¹³C-UBT at the specified follow-up.

The sponsor reported Farrington and Manning non-inferiority analyses against lansoprazole triple therapy. The registry record flags a discrepancy with unadjusted recalculations, so the sponsor’s own analysis takes precedence. The non-inferiority margin, multiplicity procedures, missing-data methods, and original sample-size rationale are not reported in the registry record. Secondary outcomes address clarithromycin-resistant infection and all participants; safety results are reported descriptively.