Topical Irrigation Therapy for CRS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Irrigation Therapy for CRS (NCT02630472), a randomized phase 1, phase 2 study. The primary outcome is Change in Microbiome Profile.

2. Clinical Question

The trial’s stated purpose was to evaluate the physiologic response to quinine-saline irrigation during an acute exacerbation after FESS. Its brief summary says investigators planned to measure clinical and quality-of-life outcomes at baseline and follow-up, then compare the randomized groups. The hypothesis recorded by investigators was that the quinine sulfate arm would perform better on all measures than the control arm. That statement describes the investigators’ expectation, not a result.

The secondary outcomes listed are change in Lund-Kennedy Endoscope Score, change in the 22-item Sinonasal Outcomes Test Score, and change in Sniffin' Stick-12 Score. The registry record does not report results for these measures. It also does not report a result for the primary microbiome endpoint. Therefore, the registry record cannot answer whether the groups differed on the planned measures.

3. Trial Design

The registry describes NCT02630472 as a randomized, double-masked, parallel-group Phase 1 and Phase 2 trial sponsored by the University of Pennsylvania. The stated enrollment is 10. The study began in 2015-10, had a primary completion date of 2017-05-04, and is listed as terminated. The record does not report why the trial was terminated.

Eligible participants were described as having previously undergone functional endoscopic sinus surgery and experiencing an acute exacerbation of uncomplicated chronic rhinosinusitis. The record lists rhinitis and sinusitis as conditions. It does not provide the full eligibility criteria, recruitment procedures, or details about how participants were randomized. It also does not report the allocation ratio or the number assigned to each arm in the design description.

The experimental intervention was quinine sulfate. Its arm description refers to 28 tubes containing 1mg/ml (6 mls total) and 28 3cc syringes with mucosal atomizing devices; the recorded application instructions are incomplete. The placebo description refers to sucrose octaacetate in tubes and syringes with mucosal atomizing devices, but its instructions are also incomplete. The brief summary describes the comparator as saline-placebo, so the registry record’s descriptions are not fully consistent. It does not report whether masking was assessed or maintained in practice.

The primary endpoint was change in microbiome profile, described as pre- and post-treatment endoscopically obtained sinonasal microbiologic cultures. The stated assessment times were baseline, Week 2, and Week 10. Secondary outcomes were changes in endoscopy, sinonasal quality-of-life, and smell-identification scores. The registry lists five outcome measures but reports no registered outcome analyses. The primary endpoint is explicitly marked as not evaluated. Results for the secondary outcomes 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This study was terminated. Partial data was collected and is misleading due to mis-dosing. This outcome measure was not evaluated.

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: No data collected, no analysis performed.

6. Primary Endpoint

The registry lists the primary outcome as Change in Microbiome Profile, measured over Baseline, Week 2, and Week 10.

The primary endpoint was change in microbiome profile, assessed through sinonasal microbiologic cultures obtained by endoscopy. The record describes cultures before and after treatment and lists baseline, Week 2, and Week 10 as the assessment times. It does not specify a particular microbiome summary, such as a named organism, diversity index, or prespecified score. It also does not report a unit or statistical parameter for the endpoint.

In general, microbiologic cultures can characterize organisms recovered from a sampled site. Repeated measurements can be used to describe change over time, while comparisons between randomized groups can address whether patterns of change differ between assigned interventions. Those are general purposes of such measurements, not findings from this trial.

The registry states that the primary outcome was not evaluated. It explains that the trial was terminated, partial data were collected, and those data were considered misleading due to mis-dosing. Consequently, the registry record contains no primary endpoint estimate, group comparison, confidence interval, or p-value. There is no reported treatment effect to interpret for this endpoint.

The endpoint’s role in the study is distinct from its observed status: it was designated as the primary measure, but designation does not mean that a valid analysis was completed. The registry record does not describe the intended microbiome processing or analysis in enough detail to identify how a change score would have been defined. It also does not report whether the stated assessment times were all completed for participants. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: The terms in this discussion describe common principles of trial design and analysis. They do not imply that a particular analysis was completed in this trial.

What does randomization contribute?

Randomization assigns participants to interventions using a chance-based process. In general, it helps prevent investigators’ or participants’ characteristics from determining assignment and supports a fair comparison of outcomes between groups. Its benefit depends on the assignment process being implemented as intended and the assigned interventions and outcomes being documented. The registry identifies this trial as randomized but does not report the sequence-generation method, concealment procedures, allocation ratio, or arm-specific assignment counts in its design description.

Randomization does not guarantee that groups will be identical, especially in a small trial, and it cannot correct errors in intervention delivery or outcome measurement. Here, the registry reports that partial data were considered misleading due to mis-dosing and that the primary endpoint was not evaluated. The record does not explain how the dosing issue arose or how it affected any participant or measurement, so its implications cannot be quantified from the registry.

What does double masking mean?

Masking is intended to reduce the possibility that knowledge of assigned intervention influences participant behavior, clinical management, outcome assessment, or reporting. Double masking indicates that the record classifies the study as masked at more than one role, but the registry does not identify precisely who was masked or describe how masking was maintained. Nor does it report whether participants or assessors could distinguish the interventions. The placebo description notes a bitter taste for sucrose octaacetate; the record does not say whether that feature affected masking.

How should a repeated-measures endpoint be understood?

The primary endpoint was described at baseline, Week 2, and Week 10. In general, repeated measurements can help characterize how an outcome changes over time. A statistical analysis might compare change from baseline, compare groups at a follow-up time, or model measurements across time. These approaches answer related but not identical questions. The registry does not report the planned statistical definition of microbiome change, a model, or a specific contrast. It therefore does not establish which estimand or analysis was intended.

For a repeated-measures analysis to be interpretable, the timing and methods of measurement should be sufficiently consistent, and the handling of observations that are absent or invalid should be described. The registry reports partial data collection and mis-dosing, but it does not identify the amount or pattern of missing observations, whether all scheduled collections occurred, or how questionable observations were treated. These details are not reported in the registry record.

What do estimates and confidence intervals usually communicate?

In general, an effect estimate describes the size and direction of a comparison on a defined scale. A confidence interval communicates the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates more precision than a wide interval, while an interval spanning values compatible with different conclusions may leave the result uncertain. A p-value, when used, describes how compatible the observed data are with a specified null model; it does not measure the probability that a treatment works.

None of these quantities is reported for the primary endpoint, which the registry says was not evaluated. The registry lists no outcome analyses. Therefore, there is no trial-specific estimate, interval, or p-value to explain, and no basis for judging statistical precision of an efficacy comparison from the posted results.

Why does the analysis population matter?

In general, trial analyses may define participants according to randomized assignment, intervention received, or availability of outcome measurements. These populations can answer different questions and can be affected differently by departures from the planned intervention. An analysis based on assignment is often intended to preserve the benefits of randomization, while analyses based on treatment received can be vulnerable to differences associated with adherence or dosing. The registry record does not report an analysis population for efficacy outcomes, and no primary outcome analysis is reported.

Because the study was terminated and its primary endpoint was not evaluated, the posted information does not show whether a complete-case analysis, an assignment-based analysis, or another approach was used. The record also does not report a missing-data method. General statistical methods cannot substitute for those trial-specific details.

What can be inferred from the adverse-event entries?

Safety summaries depend on both event counts and the participants observed for each outcome. A count of zero among a group with participants at risk has a different interpretation from a group with no participants recorded as at risk. The registry lists 10 at risk for serious adverse events in the quinine sulfate group and 0 affected; for the placebo group it lists 0 at risk and 0 affected. For other adverse events, it lists 10 at risk and 7 affected in the quinine sulfate group, and 0 at risk and 0 affected in the placebo group. No deaths are listed. The absent placebo risk denominator prevents a meaningful comparison of event frequency between the arms.

The record does not report an inferential safety analysis, exposure-adjusted rates, event timing, or event-level descriptions. These would be needed to address questions that cannot be answered by the aggregate entries alone. The observed registry counts should be described as recorded, not used to claim that an intervention caused or prevented events.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the microbiome primary outcome and secondary changes in Lund-Kennedy Endoscope Score, the 22-item Sinonasal Outcomes Test Score, and Sniffin' Stick-12 Score. It does not report an approach to multiplicity, such as a hierarchy of confirmatory tests or adjustment for testing several outcomes. Without that information, the intended interpretation of multiple statistical comparisons is not reported in the registry record.

Multiplicity is a general concern when several outcomes or time points are examined. In general, conducting multiple tests can increase the chance of finding at least one apparently notable result by chance, so a prespecified strategy can help define how evidence should be assessed. This is a general statistical principle, not a description of an analysis performed in this trial. The registry reports no outcome analyses, so there are no reported efficacy p-values to evaluate for multiplicity.

The record says partial data were collected and were misleading due to mis-dosing; it does not report the amount or pattern of missing data, reasons for missingness, or how missing observations would have been handled. The endpoint was not evaluated, and the registry does not identify an analysis population or provide an account of participants included in any efficacy analysis. These items are not reported in the registry record.

The record also does not report a statistical analysis plan, interim analyses, or a sample-size justification. It is therefore not possible to establish from the registry how the investigators intended to address missing data, multiplicity, or deviations from assigned dosing. The stated enrollment alone does not reveal the planned precision or power of the comparison.

11. 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 non-serious adverse event terms

The registry’s serious adverse-event entries list the quinine sulfate group as having 10 participants at risk and 0 affected. The placebo group is listed with 0 participants at risk and 0 affected. No deaths are listed for either group. The zero count in the placebo row should not be interpreted as evidence that no serious events occurred among placebo recipients: the registry records no participants at risk for that row.

For other adverse events, the quinine sulfate group is listed with 10 at risk and 7 affected; the placebo group is again listed with 0 at risk and 0 affected. These entries describe what the registry records, but they do not establish a comparative event frequency because the placebo denominator is absent. The record does not explain why the placebo group has zero at risk in these safety entries or whether this reflects safety-data collection, exposure, or another issue.

In general, safety counts are most interpretable when the numbers observed for each group and the event definitions are clear. The registry does not report event-level descriptions, timing, severity details for non-serious events, or a statistical comparison. The listed counts therefore should not be used to conclude that either intervention caused, prevented, or differed in risk of adverse events.

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

This record documents a randomized, double-masked, parallel-group study intended to assess quinine-saline irrigation in people with an acute exacerbation of chronic rhinosinusitis following FESS. It identifies the planned microbiome endpoint, its stated collection times, and several secondary clinical outcomes. It also records that the study was terminated and that the primary endpoint was not evaluated because partial data were considered misleading due to mis-dosing.

What the record does not establish is an efficacy result. It reports no analyzed change in microbiome profile, no group comparison for the primary outcome, and no results for the listed secondary outcomes. The investigators’ stated hypothesis does not establish the observed outcome. With no reported outcome analyses or statistical estimates, there is no reported effect size or precision to interpret.

The registry also does not establish comparative safety. Although it records adverse-event counts for the quinine sulfate group, it records no participants at risk in the placebo group. The zero affected count in that group therefore cannot be treated as a comparison showing absence of events. The posted safety information is limited to the registry entries and does not describe event types or timing.

In general, a trial’s design can indicate how investigators intended to answer a clinical question, while completed and interpretable outcome analyses are needed to estimate what happened under the studied conditions. Here, the design and objectives are documented, but the planned primary result is unavailable. The status and data-quality explanation materially limit what can be learned from the record.

These limitations do not show that quinine sulfate is effective or ineffective, nor do they establish that it is safe or unsafe. They mean that this registry record does not provide an interpretable comparative efficacy result or a balanced safety comparison. Further claims about treatment effects would exceed what the posted results support.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a planned outcome and an analyzed result. The microbiome profile was designated as the primary endpoint, with cultures described at baseline, Week 2, and Week 10. Yet the registry explicitly states that the endpoint was not evaluated. Naming an endpoint and its measurement schedule does not supply an estimate of change or a comparison between randomized groups.

The record also highlights why intervention delivery and data quality are essential to interpreting a randomized study. Random assignment can support a fair comparison, but the registry states that partial data were considered misleading due to mis-dosing. Without details about the extent and consequences of that problem, the record cannot show whether the intended intervention contrast was preserved in the collected data.

Its safety entries demonstrate another practical issue: event counts require context about who was observed. The placebo arm’s zero at-risk entries mean its zero affected counts cannot serve as a conventional comparison against the quinine sulfate arm. Reading counts without their denominators can give a misleading impression of reassurance or contrast.

Finally, the record distinguishes a study hypothesis from evidence. The investigators expected the quinine sulfate group to perform better on all measures, but the registry reports no outcome analyses to test that expectation. The statistical lesson is not a conclusion about the intervention; it is that design labels, planned endpoints, and hypotheses should not be mistaken for completed evidence. The record supports transparent description of what was intended and what was not evaluated, while leaving the treatment question unresolved.

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 central limitation is explicit in the registry: the study was terminated, partial data were collected, the data were considered misleading due to mis-dosing, and the primary outcome was not evaluated. The record does not report the reason for termination, the nature of the dosing error, when it occurred, or how much of the collected information it affected. Without those details, the consequences for interpretation cannot be assessed further.

The intervention descriptions are incomplete. The quinine sulfate instructions stop before fully describing application, and the placebo instructions are also truncated. The brief summary calls the comparator saline-placebo, while the placebo-arm description specifies sucrose octaacetate. The registry does not explain this difference. This makes it difficult to reconstruct the full intended treatment contrast from the available descriptions.

The registry reports an enrollment of 10 but does not state arm-specific assignment counts in the design description. It does not report the allocation ratio, detailed eligibility criteria, randomization procedures, or masking procedures. The record lists no outcome analyses and does not report efficacy estimates, confidence intervals, or p-values. It also does not report how missing data, protocol deviations, or participants’ analysis populations were to be handled.

The safety data have a specific denominator limitation: the placebo group is listed as having 0 participants at risk for serious and other adverse events. The registry does not explain this entry, so the safety counts do not support a direct comparison between groups. It also provides no event-level descriptions or timing.

Finally, the record does not report a multiplicity strategy, sample-size justification, interim analyses, or a statistical analysis plan. These absences limit the ability to evaluate how analyses were intended to be conducted, but they do not establish that a particular method was or was not used outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Topical Irrigation Therapy for CRS — NCT02630472.
• Registry record last updated 2019-03-13; status last verified 2019-02.
• Results first posted 2019-03-13.
• 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

NCT02630472 was a randomized, double-masked, parallel-group Phase 1 and Phase 2 trial sponsored by the University of Pennsylvania. It enrolled 10 and is listed as terminated. The study concerned quinine-saline irrigation compared with a placebo intervention for acute exacerbation of chronic rhinosinusitis after FESS.

The primary outcome was change in microbiome profile based on endoscopically obtained sinonasal cultures, with assessments specified at baseline, Week 2, and Week 10. The registry states that this outcome was not evaluated because the study was terminated and partial data were considered misleading due to mis-dosing. The record lists secondary endoscopic, sinonasal quality-of-life, and smell-identification outcomes but reports no outcome analyses.

Safety entries list 10 at risk and 0 affected for serious adverse events in the quinine sulfate group, while the placebo group has 0 recorded at risk. For other adverse events, the quinine sulfate group has 10 at risk and 7 affected, and the placebo group again has 0 at risk. No deaths are listed. These entries do not provide a balanced safety comparison. The registry record does not report an interpretable efficacy result.