Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease (NCT02216357), a randomized phase 2 study. The primary outcome is Proportion of Patients Who Experience a ≥ 20% Decrease in Forced Expiratory Volume in One Second (FEV1) Compared to Baseline Following a Dose of Investigational Medicinal Product (IMP) (Study Day 1 or 2) Prior to Initiation of the Aspirin Challenge.

2. Clinical Question

The trial addressed a safety question about oral ifetroban compared with placebo in people with a history of AERD. The primary outcome focused on whether FEV1 fell by at least 20% from baseline after a dose of investigational medicinal product, before the aspirin challenge. The primary outcome record gives Study Day 2 as its timeframe, while its title describes the dose as occurring on Study Day 1 or 2.

This question is narrower than whether the medication changes respiratory symptoms or lung function in general. It concerns a threshold-defined event over a specified period and sequence of study procedures. The registry also lists secondary outcomes involving nasal airflow, nasal symptoms, adverse events, outcomes during the aspirin challenge, rescue medication, and asthmatic reactions during treatment.

The posted primary endpoint counts are 0.0 in the ifetroban group and 0.0 in the placebo group. The registry lists 12 participants for the ifetroban primary outcome and 4 for placebo. These results describe the recorded endpoint counts; they do not establish that the groups had identical underlying risk or that the medications have equivalent safety profiles.

3. Trial Design

The registry describes a completed, randomized, Phase 2, multicenter, double-blind, placebo-controlled trial with a parallel-group model and quadruple masking. The sponsor was Cumberland Pharmaceuticals. The listed condition was aspirin-exacerbated respiratory disease (AERD). The recorded study start was 2014-08, and the primary completion date was 2016-01.

The intervention was an oral ifetroban capsule. Its arm description specifies 200 mg per dose, given once per day on Study Days 1, 2, and 3. The comparator was a matching oral placebo capsule, also given once per day on those study days. The registry records enrollment of 19. For the primary endpoint, the posted arm counts are 12 for ifetroban and 4 for placebo. The registry record does not explain how the enrollment figure relates to these endpoint counts.

Randomization indicates that assignment to study groups was by chance, as described in the registry. The record identifies the study as quadruple-masked but does not specify which groups of people were masked or how masking was maintained. It also does not report the randomization procedure, allocation concealment details, or a protocol description beyond the listed design characteristics.

The primary outcome concerns a threshold decline in FEV1 following a study-medication dose before the aspirin challenge. The record lists Study Day 2 as the outcome timeframe. Other listed outcomes cover measurements after study medication and during the aspirin challenge, as well as adverse events and rescue medication. The registry reports a completed study, but its record does not provide a fuller account of conduct, deviations, or the timing and procedures for each assessment.

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.

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 Proportion of Patients Who Experience a ≥ 20% Decrease in Forced Expiratory Volume in One Second (FEV1) Compared to Baseline Following a Dose of Investigational Medicinal Product (IMP) (Study Day 1 or 2) Prior to Initiation of the Aspirin Challenge, measured over Study Day 2.

The primary endpoint is the number of participants experiencing at least a 20% decrease in forced expiratory volume in one second (FEV1) from baseline after a dose of study medication, before the aspirin challenge. The endpoint title refers to a dose on Study Day 1 or 2, and its recorded timeframe is Study Day 2.

FEV1 is a measure of how much air a person can forcefully exhale in the first second of an expiratory maneuver. In general, lung-function measures can provide an objective way to characterize respiratory changes. A threshold endpoint turns a continuous measurement into a yes-or-no event: the participant either meets the specified decline criterion or does not. That makes the outcome interpretable as an event count, but it also discards information about changes that do not cross the threshold.

The endpoint was chosen to address the study’s stated safety objective before the aspirin challenge. It records a decline following study medication during the specified assessment period, rather than every possible change in respiratory status or every adverse event. The primary outcome counts are 0.0 in the ifetroban arm and 0.0 in the placebo arm, with reported endpoint counts of 12 and 4, respectively. Those counts alone do not describe the precision of a treatment comparison; the registry record does not provide an estimable two-arm comparison for this binary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary: each participant is classified according to whether the specified FEV1 decline occurred. Binary outcomes are commonly summarized as event counts and the number of participants assessed. Here, the posted counts are 0.0 for ifetroban and 0.0 for placebo, with endpoint counts of 12 and 4. The record does not provide an estimable two-arm comparison for this endpoint.

What does a binary outcome capture?

A threshold-based outcome converts a measurement into an event indicator. This can make a clinically defined threshold easier to summarize than a set of continuous measurements, but it loses information about the size of changes that remain below the threshold. Two participants with different FEV1 changes can receive the same classification if neither crosses the event threshold. Conversely, a small shift around the cutoff can change the classification. These are general properties of dichotomizing a continuous measure, not additional findings from this trial.

Counts and denominators are essential for interpreting a binary result. An event count indicates how many participants met the criterion among those counted for the outcome. A comparative analysis can then estimate a contrast between groups, with uncertainty reflecting the amount and pattern of data. In this registry record, the comparison is marked as missing or not estimable. The zero counts therefore remain descriptive rather than a basis for a reported comparative estimate.

Why does zero events in both groups need cautious interpretation?

When neither group has an observed event, the data do not show a difference in observed event counts. However, that is not evidence that the underlying event risks are identical. General statistical methods for binary outcomes can behave differently when event counts are sparse or zero, and some standard estimates may not be defined without special handling. The record does not state which approach, if any, was considered for such a situation. No unreported estimate should be inferred from the counts.

A confidence interval, when reported, describes the range of values compatible with the data under a specified statistical model and procedure. It communicates uncertainty in addition to the point estimate. No confidence interval for the primary comparison is reported in the registry record, so the precision of a comparative effect cannot be assessed from that record.

What analysis details are available?

The registry identifies the endpoint as a participant count and records the trial as randomized, placebo-controlled, and parallel-group. It does not report the primary statistical test or model, the planned estimand, covariate adjustment, handling of repeated measurements, or a formal analysis plan. The record lists zero analyses. Those omissions mean that the statistical procedure intended for the primary comparison cannot be reconstructed from the registry record.

General principles for trial analysis distinguish the outcome definition from the analysis method. A complete analysis description would clarify which participants were included, how missing outcome measurements were handled, and how treatment assignment was used. These details are not reported in the registry record. The endpoint counts should therefore be read as posted summaries, not as a complete account of a prespecified analysis.

How should planning illustrations be read?

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The stated target effect is a fraction of the observed effect. Such illustrations are planning scenarios, not observed power and not evidence that the trial had a particular probability of detecting an effect. The assumptions do not establish the trial’s original design rationale; that rationale is not reported in the registry record.

For general interpretation, planning calculations depend on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis method. If an observed effect is based on sparse or zero-event data, a planning illustration tied to that effect can be unstable or difficult to interpret. The registry’s illustration should not be treated as an independent confirmation of the observed result. It does not replace an analysis of the trial data or provide a comparative estimate for the primary endpoint.

Overall, the available information supports a straightforward description of the posted event counts. It does not support reconstruction of an inferential analysis, an assessment of its assumptions, or a quantitative statement about the uncertainty in the treatment comparison.

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("Ifetroban, Oral Capsule", "Placebo, Oral Capsule")
n      <- c(12, 4)
events <- c(0, 0)
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  Ifetroban, Oral Capsule  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7
ARM  Placebo, Oral Capsule  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 9 posted secondary outcomes, in addition to the primary endpoint. The secondary outcomes cover nasal airflow and symptom thresholds after study medication and during the aspirin challenge, treatment-emergent adverse events, asthmatic reactions, rescue medication, and other challenge-related measures. Examining multiple outcomes can raise a general multiplicity issue: when many statistical hypotheses are tested, the chance of at least one apparently notable result can increase. Whether and how to address that issue depends on the planned analyses and the purpose of each outcome.

A multiplicity adjustment or hierarchy for outcomes is not reported in the registry record. The record also does not provide analysis results for the secondary outcomes in the information available for this account. The presence of multiple listed outcomes alone does not establish that each was tested or that any particular adjustment was used.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not specify whether the primary analysis was based on all randomized participants, participants who received study medication, or another defined group. It does not explain the difference between overall enrollment of 19 and primary outcome counts of 12 and 4, or state whether missing outcome observations, exclusions, or other factors account for that difference.

These omissions limit interpretation of both the endpoint summary and any comparison between arms. The posted count remains useful as a description of the registry result, but the record does not permit a full assessment of missingness, population definitions, or control of multiplicity.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s adverse-event summary reports no serious adverse events in either arm and no deaths in either arm. For other adverse events, the summary records 11 affected participants among 12 at risk in the ifetroban group and 4 among 4 at risk in the placebo group. These are counts from the posted safety summary and should not be read as a complete description of event types, timing, duration, or severity.

A serious adverse event is a safety classification, while the summary’s other adverse-event count is a separate category. The registry lists no serious-event terms. It does not provide the detailed event-level information needed to evaluate what the non-serious events were, whether participants had more than one event, or how events were judged in relation to study medication.

These figures are descriptive and do not establish that one treatment is safer than the other. The safety groups have different reported counts at risk, and the registry record does not provide a comparative statistical analysis or uncertainty estimates for these outcomes. Zero serious events and zero deaths in the posted summary do not establish that such events cannot occur. They describe only the recorded safety experience in this study record.

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

The primary result describes the number of participants meeting a prespecified FEV1-decline threshold after study medication and before the aspirin challenge. The posted count is 0.0 in each arm. This is a limited description of one endpoint at one specified stage of the study; it is not a broad assessment of every respiratory or safety outcome.

The result does not show that ifetroban and placebo have the same underlying risk. A finding of no observed events in either group is not an equivalence test, and the registry does not report an estimable comparative result, confidence interval, or other uncertainty measure for the primary endpoint. It also does not establish that no participant could experience the event outside the observed study data.

Nor does this endpoint answer the trial’s other listed questions. The registry includes outcomes related to nasal airflow, nasal symptom scores, treatment-emergent adverse events, responses during the aspirin challenge, rescue medication, and asthmatic reactions during treatment. The primary counts cannot be used as substitutes for results on those measures.

The study is recorded as completed and randomized, but the registry record does not include the analysis details needed to determine how missing outcomes or analysis populations were handled. Overall enrollment is 19, while the endpoint counts are 12 and 4; the record does not explain this difference. These details constrain how fully the result can be evaluated.

The appropriate reading is therefore descriptive: no participants in either reported primary-outcome group were recorded as meeting the event threshold. That statement should not be extended into a claim that the treatments are equivalent, that one is safer, or that the result settles the broader safety question.

14. Why This Trial Matters Statistically

This trial illustrates why event counts need context. A binary safety endpoint can be easy to state, but zero recorded events in both groups do not by themselves establish that the underlying risks are equal. Comparative inference depends on the number of participants assessed, the analysis method, and the uncertainty around the result. The registry gives endpoint counts but marks the two-arm comparison as missing or not estimable.

The record also highlights the difference between a study’s total enrollment and the counts attached to a particular outcome. Enrollment is listed as 19, while the primary endpoint counts are 12 and 4. Without an explanation of that relationship, readers cannot determine from the registry record which participants contributed to the endpoint or why the counts differ.

Multiple outcomes further shape interpretation. The registry lists a primary endpoint and 9 secondary outcomes addressing different measurements and periods. In general, results across several outcomes need to be understood in light of the analysis plan and any approach to multiplicity. Those details are not reported in the registry record.

Finally, the presence of a planning illustration does not repair gaps in the trial’s inferential reporting. A planning scenario is distinct from an observed treatment comparison and from observed power. Statistical interpretation is strongest when outcome definitions, analysis populations, missing-data handling, comparative estimates, and uncertainty are all clear. This record offers a focused example of how a plausible descriptive result can coexist with substantial limits on comparative interpretation.

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 principal trial-specific limitation is that the registry does not report an estimable two-arm comparison for the primary binary endpoint. Although the posted event counts are 0.0 in both groups, no comparative estimate or confidence interval is available in the registry record. The precision of any treatment contrast therefore cannot be assessed from the posted primary result.

The registry records overall enrollment of 19, but the primary endpoint counts are 12 for ifetroban and 4 for placebo. The record does not explain this difference. It does not state whether the endpoint counts reflect missing assessments, exclusions, a defined analysis population, or another reason. No assumptions about those possibilities can be confirmed from the record.

The primary endpoint description refers to assessment following a dose on Study Day 1 or 2, while the outcome timeframe is listed as Study Day 2. The registry does not clarify this wording. It also does not give detailed assessment procedures, a statistical analysis plan, the method for handling missing data, or the analysis populations.

Although secondary outcomes and safety summaries are listed, the record does not provide a full set of results or comparative analyses for them in the information. Adverse-event counts do not include detailed event descriptions or timing. The record also does not report a multiplicity strategy. These limitations narrow what can be concluded from the posted information to a description of recorded counts, rather than a comprehensive evaluation of comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease — NCT02216357.
• Registry record last updated 2017-05-15; status last verified 2017-04.
• Results first posted 2017-03-22.
• 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 describes a completed, randomized, Phase 2, multicenter, double-blind, placebo-controlled parallel-group trial of oral ifetroban in patients with a history of AERD. It records quadruple masking, sponsor Cumberland Pharmaceuticals, study start 2014-08, primary completion 2016-01, and enrollment of 19.

The primary endpoint was a threshold decrease in FEV1 after study medication and before the aspirin challenge. The posted event counts are 0.0 for ifetroban and 0.0 for placebo, with endpoint counts of 12 and 4. A two-arm comparison is marked missing or not estimable. The registry also lists 9 secondary outcomes and safety counts, including no serious adverse events and no deaths in either group.

The record does not explain the relationship between enrollment and endpoint counts, or report the analysis populations, missing-data methods, or a comparative estimate with uncertainty for the primary outcome. The posted result is therefore best read as a descriptive account of the recorded counts, not as evidence of equivalence or a definitive comparative safety conclusion.