Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis (NCT02416102), a non-randomized phase 4 study. The primary outcome is Change in Nasal Potential Difference (NPD)..

2. Clinical Question

The study asked whether losartan was associated with a change in nasal potential difference (NPD) in groups differing in smoking history and COPD status. The registry describes healthy non-smokers, smokers without COPD, and ex-smokers with COPD. The primary outcome was planned for assessment at baseline and 8 weeks. The registry’s stated purpose also refers to cigarette smoke-induced lung injury in smokers and ex-smokers with and without COPD.

The distinction between the research question and the available result is important. The intervention schedule and planned measurement can be described, but they do not establish whether NPD changed. The registry reports that nasal sample data for all participants were unavailable for analysis because readings were uninterpretable. Without analyzable measurements, there is no posted estimate of change, uncertainty interval, or statistical test for this primary outcome. The record also does not report results for the listed secondary outcomes, change in IL-8 concentrations and percent change in TGF-ß mRNA expression. The study therefore documents a planned biological question and a measurement problem, rather than an interpretable answer about the primary endpoint.

3. Trial Design

The registry identifies this as a phase 4, non-randomized, unmasked crossover study. It lists enrollment of 31 and describes three cohorts: healthy non-smokers, smokers without COPD, and ex-smokers with COPD. Each cohort description says 10 participants would receive losartan 50 mg for 4 consecutive weeks followed by losartan 100 mg for 4 consecutive weeks. These descriptions are plans, not evidence that every participant completed both periods. Completion by cohort is not reported in the registry record.

A crossover design generally means participants receive interventions in successive periods, allowing observations from the same participant to be related across periods. That feature can be useful when within-person change is of interest. Here, however, the registry describes the same dose order for each listed cohort and does not describe a placebo or untreated comparison period. The record does not report a washout period, the rationale for the sequence, or whether the analysis accounted for period or carryover effects. Those details are not reported in the registry record.

Non-randomized allocation also affects interpretation. The registry expressly notes that the arms are not a like-for-like control comparison. The groups are defined by smoking and COPD history, so differences between them cannot automatically be attributed to treatment or to a single group characteristic. Masking is listed as none. The record does not describe how participants entered the cohorts or how treatment adherence was assessed.

The study is marked terminated. Its recorded start date is 2016-03-31, and its primary completion date is 2017-04-03. These dates describe the registry timeline; they do not explain why the study was terminated. A reason for termination is not reported in the registry record. Most importantly for interpreting the design, the primary readings were not analyzed because they were uninterpretable. The intended crossover structure therefore does not yield a reported treatment estimate in the posted results.

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

Analysis population for the primary outcome, as defined in the registry: Nasal sample data for all participants were not available as the readings were uninterpretable and not further analyzed.

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: There was a difficulty in recruitment ex-smokers with COPD prior to study termination

6. Primary Endpoint

The registry lists the primary outcome as Change in Nasal Potential Difference (NPD)., measured over Baseline, 8 weeks.

The primary endpoint is titled “Change in Nasal Potential Difference (NPD).” The registry specifies measurement at baseline and 8 weeks and says NPD was assessed from nasal cells collected using sterile cytology brushes. The unit, statistical parameter, and measure of dispersion are not reported in the registry record. No numerical change is posted.

In general, a physiological measurement can serve as an intermediate endpoint when researchers want to examine a biological process rather than a symptom, functional outcome, or clinical event. NPD is a measurement of electrical potential at the nasal epithelium; in general, such measurements can be used to study epithelial ion transport. The study’s title and stated purpose connect this measurement to airway mucociliary dysfunction. That connection explains why a nasal physiological measure was selected, but it does not make NPD itself a direct measure of every aspect of airway function or of a participant’s clinical experience.

For a change endpoint, interpretation ordinarily depends on the measured value at the specified time points and a defined method for summarizing the change. The registry does not report an analyzed baseline-to-follow-up difference. It states that nasal sample data for all participants were unavailable because readings were uninterpretable and not further analyzed. Consequently, neither the size nor direction of change can be described from this record. The endpoint’s intended timing and collection approach are documented, but its observed result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a non-randomized, unmasked crossover design. In general, randomization helps balance measured and unmeasured participant characteristics across treatment groups, on average. Without random allocation, group membership may be associated with characteristics that also relate to an outcome. Here, the cohorts are defined by smoking and COPD history, and the registry specifically cautions that the arms are not like-for-like control comparisons. A difference between cohort summaries, if such summaries were available, would therefore need cautious interpretation and could not automatically be assigned to losartan.

What does a crossover design contribute?

In general, a crossover design observes participants through successive treatment periods. Comparing measurements within a participant can account for some characteristics that remain relatively stable over the study. But this advantage depends on the order of treatments, timing of measurement, and assumptions about effects carrying from an earlier period into a later period. The registry describes losartan 50 mg for 4 consecutive weeks followed by losartan 100 mg for 4 consecutive weeks. It does not describe an alternate sequence, a washout period, or an untreated comparison. The record also does not say whether period effects or carryover were assessed. Those design details matter because a difference between period measurements might reflect more than dose alone.

What can the primary analysis show?

For the planned primary endpoint, the key comparison would involve NPD at baseline and 8 weeks, summarized according to a prespecified statistical approach. In general, an analysis might report the estimated change, its uncertainty, and a test of a defined hypothesis. The registry does not state the statistical parameter or unit for this endpoint. More importantly, it says the readings were uninterpretable and not further analyzed. Therefore, no such estimate, uncertainty measure, or test is available in the posted results.

In general, an estimate describes the observed magnitude and direction of an effect, while a confidence interval describes its precision under the chosen model and assumptions. A narrow interval indicates greater precision than a wide interval, but an interval does not correct problems in measurement or design. Here, no interval can be interpreted because there is no reported primary estimate. It is not appropriate to treat missing or uninterpretable readings as a measured value or to infer that the true change was absent.

Why does over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. For outcomes such as counts, ignoring over-dispersion can make uncertainty look smaller than it is. This is a general statistical issue, not a reported feature of this study. The registry does not give a numerical primary outcome, a variance estimate, or an analysis model from which over-dispersion could be assessed. It would therefore be speculative to claim that this issue affected the trial’s results.

How should the planning illustration be read?

The registry describes its sample-size assumptions as a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event displays refer to participants per arm for 80% power; time-to-event displays refer to total events. These are assumptions for an illustration, not reported features of the trial’s own design or a justification for its enrollment.

A planning calculation asks how much information a future study might need to detect an effect under specified assumptions. It is not an estimate of the chance that this completed study found an effect, and it is not observed power. The primary readings were not analyzed, so the registry record does not furnish an analyzable observed primary effect to anchor a meaningful interpretation of such an illustration. The stated assumptions also refer to equal allocation between two arms, whereas this trial is described as three non-randomized cohorts receiving a sequence of doses. The illustration should not be mistaken for the trial’s actual design.

What is not documented?

The registry does not report a statistical analysis plan, a model for the crossover measurements, a sample-size justification, or interim analyses. It does not describe handling of period effects, carryover, or missing measurements beyond stating that the NPD readings were uninterpretable and not analyzed. These omissions do not prove that no such procedures existed outside the registry record. They mean that readers cannot assess them from the posted information. The most defensible statistical reading is therefore descriptive: the study had a stated endpoint and schedule, but no analyzable primary result is reported.

10. Multiplicity, Missing Data and Analysis Populations

The record lists the primary outcome as change in NPD and lists change in IL-8 concentrations and percent change in TGF-ß mRNA expression as secondary outcomes. Considering multiple outcomes can raise a multiplicity issue: in general, testing several hypotheses creates more opportunities for apparently notable findings unless the analysis plan specifies how results will be interpreted or adjusted. The registry does not report a multiplicity strategy, hierarchy among secondary outcomes, or a statistical analysis plan. No adjustment or unadjusted testing should be inferred.

The primary outcome has a specific data problem rather than a reported numerical result: NPD readings were uninterpretable and not further analyzed. The record says nasal sample data for all participants were unavailable for analysis. It does not explain the technical cause of uninterpretable readings, identify which collection or reading steps failed, or state whether any alternative endpoint analysis was attempted. These details are not reported in the registry record.

In general, missing-data methods rely on assumptions about why observations are missing and how the observed data relate to the unobserved values. The registry does not report an imputation method, sensitivity analysis, or analysis population for NPD. Because the stated readings were not interpretable, treating them as ordinary numeric missing values would require details that are not available. The record also does not report participant flow by cohort, completion of both treatment periods, or the number contributing to secondary outcome analyses.

The registry enrollment is 31, while the cohort descriptions each state 10 participants. The record does not explain the relationship between those planned cohort descriptions and the final enrollment or give a participant disposition that would reconcile them. It is therefore not possible to determine from the posted information how many participants completed the schedule or contributed usable data to each outcome. The study’s analysis populations, if defined, are not reported in the registry record.

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 0% reporting threshold.

The registry reports serious and other adverse-event counts by group. For healthy non-smokers, 16 participants are listed at risk, with 0 serious events, 0 other events, and 0 deaths. For smokers without COPD, 15 are listed at risk, with 0 serious events, 0 other events, and 0 deaths. For ex-smokers with COPD, 0 participants are listed at risk, with 0 serious events, 0 other events, and 0 deaths. No serious adverse-event terms are listed.

These are registry counts, not a complete characterization of safety. In particular, the COPD cohort has no participants listed at risk in the adverse-event results. The zero event count for that group therefore does not describe observed safety experience among an exposed group. The record does not provide an adverse-event observation period, details of exposure by dose, event ascertainment procedures, or explanations for the listed at-risk counts. Those details are not reported in the registry record.

In general, a count of zero recorded events is not proof that an event cannot occur. Interpretation depends on how many participants were observed, for how long, and how events were collected and classified. The figures should be read as the posted adverse-event counts within the listed groups, not as a comparative safety analysis. No treatment advice or broader safety conclusion follows from these counts alone.

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

The record establishes that investigators planned to study a physiological endpoint in groups defined by smoking and COPD history while participants received losartan in a stated dose sequence. It also establishes that the study was non-randomized, unmasked, and terminated, and that the primary NPD readings were considered uninterpretable and not further analyzed. These registry entries describe the study and its reporting status.

The record does not establish the direction or size of a change in NPD. It does not show whether losartan altered NPD, whether the two dose periods differed, or whether outcomes differed among the cohorts. No analyzed primary estimate or result for the listed secondary outcomes is posted. The absence of those results should not be described as a positive finding, a negative finding, or proof of no effect.

In general, a treatment-effect claim needs a defined comparison and analyzable outcome data. This study’s non-randomized cohorts do not provide a like-for-like control comparison, as the registry itself notes. The listed schedule has no described placebo or untreated period. Even if a physiological difference had been available, interpreting it as a causal effect would require careful attention to the design, analysis, and possible alternative explanations. The necessary primary result is absent.

The posted safety figures are also limited. They describe zero recorded adverse events in the groups with participants listed at risk, while no participants are listed at risk in the ex-smokers-with-COPD group. These counts cannot establish an absence of risk or support a comparative safety conclusion. They must be interpreted alongside the missing information about observation and event collection.

In practical terms, this registry entry is informative about the planned question and the failure to obtain interpretable primary readings, but not about the primary outcome’s effect estimate. A planning illustration, if shown elsewhere on the page, is not a substitute for results: it describes requirements under assumptions and is not observed power or evidence of an effect. The distinction between an unreported or unanalyzed result and a measured result without a statistically significant finding is essential for accurate reading.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates how a clearly stated endpoint can remain unanswerable when measurements cannot be interpreted. The registry specifies a primary outcome, its timing, and a collection description, yet reports that the readings were uninterpretable and not analyzed. Without usable measurements, statistical methods cannot recover an observed effect estimate from the registry entry. This is a data-availability limitation before it is a question of which statistical test to use.

The design also makes the comparison structure important. A crossover schedule can support within-participant comparisons in general, but interpretation depends on period order, carryover, and the presence of an appropriate comparison. The registry describes a fixed losartan sequence and non-randomized cohorts, and it cautions that the groups are not like-for-like controls. The record does not provide the analysis details needed to evaluate the intended within-participant comparison or separate treatment effects from other influences.

The entry also demonstrates why a study’s aim, design, and result must be kept distinct. The stated purpose concerns cigarette smoke-induced lung injury, while the primary endpoint is a change in NPD. The biological rationale does not replace an analyzed endpoint, and a planned endpoint does not guarantee that a result will be available. Here, no numerical primary outcome or secondary outcome result is posted.

Finally, this record shows why adverse-event counts require denominators and context, and why zero counts should not be treated as proof of no risk. The group with ex-smokers with COPD has no participants listed at risk. The entry therefore has limited safety information for that cohort. For readers, the key statistical lesson is to identify what was measured, whether it was analyzable, what comparison was actually available, and what uncertainty can be quantified. In this case, the primary effect and its precision cannot be quantified from the registry record.

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 most consequential limitation is that all primary NPD sample data are described as unavailable because readings were uninterpretable and not further analyzed. No estimate, unit, dispersion measure, or group-specific result is posted. The reason the readings were uninterpretable and whether any remedial procedures were attempted are not reported in the registry record. This prevents assessment of the primary outcome and its precision.

The non-randomized allocation limits causal interpretation, and the registry explicitly says that the arms are not like-for-like control comparisons. The study is unmasked, and no placebo or untreated comparison is described. Cohort differences in smoking and COPD history may be relevant to outcome differences, but the registry does not report an analysis that separates those factors from treatment or time effects.

The crossover description gives the dose sequence and durations, but does not report a washout period, alternate sequence, assessment of carryover, or statistical handling of period effects. The record also does not report adherence, treatment completion, participant flow by cohort, or the analysis population for the outcomes. These omissions make it difficult to assess how closely the conducted study followed the described schedule or how many observations would have been available for analysis.

The listed secondary outcomes have no posted results, and the registry does not report a multiplicity plan or statistical analysis plan. The listed adverse-event counts have limited context, including no participants at risk in the ex-smokers-with-COPD group. The reason for termination and any explanation of the difference between enrollment of 31 and cohort descriptions of 10 participants each are not reported in the registry record. These limitations leave important questions unresolved without indicating what the missing information would have shown.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis — NCT02416102.
• Registry record last updated 2020-08-20; status last verified 2020-08.
• Results first posted 2020-08-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This is a phase 4, non-randomized, unmasked crossover study listed as terminated. The registry records enrollment of 31 and describes healthy non-smokers, smokers without COPD, and ex-smokers with COPD. Each cohort description specifies losartan 50 mg for 4 consecutive weeks followed by losartan 100 mg for 4 consecutive weeks.

The primary endpoint was change in NPD from baseline to 8 weeks. The registry says the nasal readings were uninterpretable and were not further analyzed, leaving no reported primary effect estimate. The listed secondary outcomes are change in IL-8 concentrations and percent change in TGF-ß mRNA expression; their results are not posted. Adverse-event counts are reported for the listed groups, but the ex-smokers-with-COPD group has 0 participants listed at risk. The record does not support a quantitative conclusion about the primary outcome or a comparative safety conclusion.