Effect of Hypertonic Saline on Mucus Clearance in Children Ages 5-12 With Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Hypertonic Saline on Mucus Clearance in Children Ages 5-12 With Cystic Fibrosis (NCT01031706), a randomized na study. The primary outcome is Change in Mucociliary Clearance Rate.

2. Clinical Question

This is a question about a sustained change in a physiological measure, not about a clinical event such as an exacerbation. The registry summary says previous work in adults had demonstrated effects on exacerbation frequency and lung function, while benefit in young patients was uncertain. Those statements explain the rationale; they are not findings from this children’s trial.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group study comparing hypertonic saline with placebo. It lists the phase as NA and the status as completed. The sponsor was University of North Carolina, Chapel Hill. The study started in 2009-09, and primary completion was 2012-07.

The registry lists 23 participants enrolled. The posted primary-outcome mean estimates include 12 participants in the hypertonic saline group and 8 in the placebo group. The primary outcome population is described as all subjects with available data analyzed. Thus, the outcome estimates are based on fewer participants than the overall enrollment. The registry record does not report why data were unavailable for some enrolled participants or how missing measurements were handled.

The active arm received 6% NaCl, 4 ml TID via eFlow; the placebo arm received 0.12% x 4ml via eFlow nebulizer. The planned treatment period was 4 weeks, and the primary measurement was taken 8-12 hours after the final dose. The design therefore aimed to assess persistence beyond the immediate dose rather than only an acute response.

The brief summary describes a relatively short, placebo controlled study and identifies lung function and mucociliary clearance as key outcome measures. The registry lists FEV1 (Spirometry) Change as a secondary outcome. It does not report the randomization procedure, details of how masking was maintained, the sample-size justification, or the full statistical analysis plan. Those details should not be inferred from the randomized and quadruple-masked labels.

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: All subjects with available data 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: Number of subjects passing screening

6. Primary Endpoint

The registry lists the primary outcome as Change in Mucociliary Clearance Rate, measured over Baseline versus after completion of 4 week treatment period.

The primary endpoint is change in mucociliary clearance rate, expressed as percent clearance. The registry defines MCC90 as average radio tracer clearance through 90 minutes and identifies it as the primary index of mucociliary clearance at each study. The endpoint is the absolute change between baseline and the end of the treatment period.

Mucociliary clearance is a physiological measure of how effectively mucus and material carried with it move through the airways. In cystic fibrosis, mucus clearance is of interest because airway mucus retention is part of the disease context. As a general statistical and clinical concept, a physiological measure can capture a biological response without necessarily demonstrating a change in symptoms, exacerbations, lung function, or other outcomes that matter directly to patients. Those outcomes require their own measurements and analyses.

The timing is part of the endpoint’s interpretation. The registry says MCC was measured 8-12 hours after the final dose, and describes the primary outcome as reflecting sustained impact. That timing distinguishes the intended measure from clearance observed immediately after a dose. It does not, by itself, establish how long any observed change persists beyond that assessment.

The posted mean change was 2.77 percent clearance in the hypertonic saline group and -2.35 percent clearance in the placebo group. The posted standard errors describe precision of those group means, not the spread of individual participants’ measurements. The registry record does not report a confidence interval or an estimable two-arm comparison for this continuous endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as continuous and reports its mean and standard error for each group. A continuous measure can take values across a scale rather than being limited to categories. Here, the scale is percent clearance, and the reported outcome is change from baseline to the end of the 4 week treatment period. A mean summarizes the average change among the participants included in that arm’s estimate.

The standard error is a measure of the statistical precision of an estimated mean. In general, smaller standard errors indicate less sampling uncertainty around the mean, while larger standard errors indicate more uncertainty. They do not describe the full distribution of individual outcomes. For that, measures such as a standard deviation or a plot of participant-level values may be useful; neither is included in the reported primary outcome summaries. The standard errors are 0.98 for hypertonic saline and 1.82 for placebo.

For a randomized two-arm study, the central treatment-effect question is usually expressed as a contrast between groups. The within-group mean changes answer how the analyzed participants in each arm changed on average. A between-group contrast addresses whether those changes differed between arms. The record marks a two-arm comparison as missing or not estimable for this continuous outcome. Accordingly, no sponsor-reported contrast, test statistic, p-value, or confidence interval is available. It would not be appropriate to infer the comparative uncertainty by treating the two group summaries as if they were themselves a test.

In general, a confidence interval gives a range of values compatible with the data and the assumptions of an analysis, and communicates uncertainty about an estimate. For a treatment contrast, the relevant interval would be one around the between-group effect. No such interval is reported in the registry record. A confidence interval is not a guarantee that the true effect lies within its limits, and its interpretation depends on the analysis and assumptions used.

Random allocation is intended, in general, to make treatment groups comparable on average with respect to both measured and unmeasured factors. The registry labels the allocation randomized, and the design parallel-group. It does not report the sequence-generation method, allocation concealment details, or the analysis model. Quadruple masking is recorded, but the record does not specify which roles were masked or the procedures used to maintain masking. No details about covariate adjustment or other analysis choices are reported.

Over-dispersion is a general concern when variation in observed outcomes is greater than a statistical model expects. If a model underestimates variability, standard errors may be too small and uncertainty may be understated. The posted summaries do not identify a model-based comparison or describe a dispersion assessment, so there is no basis to say whether over-dispersion was evaluated or relevant to the sponsor’s analysis.

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning exercises, not observed power and not evidence that the trial was adequately powered. The record does not report the trial’s own sample-size justification, the target effect used in its original design, or numerical planning estimates. Planning for a fraction of an observed effect is a way to explore how assumptions about the effect size influence a future study’s required enrollment; it does not change the observed trial results.

Recalculated results, when available, would be simple unadjusted calculations from posted summary statistics and would not replace the sponsor’s own analysis. No recalculated comparison is presented for this endpoint because the record marks the two-arm comparison as missing or not estimable. The registry does not report an alternative inferential analysis that could be used instead.

For interpretation, it is important to separate the reported endpoint summaries from general statistical concepts and from unreported analysis choices. The numerical results are the arm-specific mean changes, standard errors, and sample counts. A comparative estimate with uncertainty, the handling of missing observations, and any adjustments to the analysis are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Hypertonic Saline", "Placebo")
n   <- c(12, 8)
m   <- c(2.77, -2.35)
sp  <- c(0.98, 1.82)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Hypertonic Saline  12  2.770  3.395  0.613  4.927
CARM  Placebo  8  -2.350  5.148  -6.654  1.954

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies FEV1 (Spirometry) Change as a secondary outcome. It reports no analyses. The available primary result is a pair of group summaries, while the two-arm comparison for the continuous endpoint is marked missing or not estimable. Results for the secondary outcome are not reported in the registry record.

Multiplicity arises, in general, when several outcomes, time points, or statistical tests are examined. Testing multiple questions can increase the chance of finding an apparently notable result by chance, so a statistical plan may specify a primary endpoint and methods for handling additional tests. The registry identifies a primary endpoint and one secondary outcome, but does not report a multiplicity strategy, a hierarchy among outcomes, or the number of tests performed. No multiplicity-adjusted conclusion can be drawn from the available record.

The primary outcome population is described as all subjects with available data analyzed. The posted primary means have 12 participants in the hypertonic saline group and 8 in the placebo group, while overall enrollment was 23. The registry record does not report why outcome data were unavailable, whether missingness differed by arm, or whether any imputation or sensitivity analysis was used. It also does not report a detailed analysis population definition beyond the available-data description.

In general, complete-case analyses can be vulnerable to bias if the participants with observed outcomes differ systematically from those without them. This is a methodological possibility, not a demonstrated problem in this study. Without the reasons for missingness and additional analyses, the effect of unavailable measurements cannot be assessed.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts were 0 among 14 participants at risk in the hypertonic saline group and 0 among 9 participants at risk in the placebo group. These are the posted group counts; they do not establish that serious events could not occur, and the registry record does not report a comparative safety analysis.

For other adverse events, the record lists 11 affected participants among 14 at risk in the hypertonic saline group and 9 affected participants among 9 at risk in the placebo group. These are participant counts, not event totals, and the record does not give the specific non-serious event terms in the listed safety summary. The counts alone do not describe severity, duration, relationship to treatment, or whether an individual had more than one event.

Deaths are not reported in the registry record. The absence of a posted death count should not be interpreted as a count of zero. Likewise, zero serious adverse events in the recorded groups does not mean there was no safety monitoring or that no other adverse experiences occurred. Safety counts are descriptive and should be interpreted alongside the limited group sizes and the information the record actually reports.

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

The posted primary outcome gives average changes in MCC90 for participants with available data: 2.77 percent clearance in the hypertonic saline group and -2.35 percent clearance in the placebo group. The corresponding standard errors are 0.98 and 1.82. These values describe arm-specific means and their precision, but the registry does not provide an estimable two-arm comparison for the continuous endpoint.

That distinction matters. The scientific question concerns how outcomes compare between randomized groups, not only whether each group’s average moved from baseline. Without a reported comparative estimate and its uncertainty, the posted summaries cannot establish the size or precision of a treatment contrast. They also do not establish statistical significance or a clinically meaningful effect.

The endpoint is a physiological measure of mucociliary clearance assessed after treatment, with the measurement scheduled 8-12 hours after the final dose. It can inform the study’s question about sustained change in this measure. It does not, by itself, demonstrate a change in lung function, symptoms, exacerbations, or other clinical outcomes. The registry lists FEV1 (Spirometry) Change as a secondary outcome, but its result is not reported in the registry record.

The study enrolled 23 participants, while the posted primary means are based on 12 participants in one arm and 8 in the other. The record describes the analysis population as subjects with available data and does not explain missing observations. That limits assessment of how well the endpoint estimates represent all randomized participants.

The results therefore support a narrow description of the available outcome data, not a conclusion that hypertonic saline does or does not produce a clinically important benefit. The registry record does not report the analysis needed to quantify the between-group effect, nor does it provide enough information to resolve uncertainty about missing data or other outcomes.

14. Why This Trial Matters Statistically

This trial illustrates a key distinction in clinical-trial reporting: group-level changes are not the same as a treatment-effect estimate. The reported means describe the average change within each arm, but the registry does not report an estimable two-arm comparison for the primary continuous endpoint. A reader therefore has descriptive summaries without the comparative estimate needed to judge the magnitude and precision of the randomized contrast.

The endpoint also makes the timing of measurement important. MCC90 was assessed 8-12 hours after the final dose, and the investigators characterized the primary outcome as reflecting sustained impact. This makes the question more specific than whether a response occurs during or immediately after administration. It also shows why a clear endpoint definition needs to include both what is measured and when it is measured.

The difference between overall enrollment and the sample counts attached to the endpoint estimates highlights the importance of reporting analysis populations and missing data. The record says that subjects with available data were analyzed, but does not explain why some outcomes were unavailable. Without those details, readers cannot assess whether the available-case summaries may differ from what would have been seen with complete follow-up.

Finally, the record lists a secondary lung-function outcome but does not report its result, and it does not provide a multiplicity strategy or detailed statistical plan. These omissions limit synthesis across outcomes and make the primary results harder to place in a complete analysis framework. The example is a reminder that numerical summaries, transparent analysis methods, and uncertainty estimates serve different purposes; a mean and standard error alone do not answer every clinical-trial question.

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 posted primary-outcome evidence is limited to arm-specific means, standard errors, and sample counts. The registry marks values as missing or not estimable for a two-arm comparison of the continuous endpoint. No between-group estimate, confidence interval, or test result is reported, preventing assessment of comparative uncertainty from the registry record.

Overall enrollment was 23, while the endpoint summaries use 12 participants in the hypertonic saline group and 8 in the placebo group. The record does not explain the unavailable outcome data, report reasons for withdrawal or nonmeasurement, or describe an approach to missing observations. It is therefore not possible to assess whether the analyzed participants differed from those without available data.

The registry does not report the original sample-size justification, detailed statistical analysis plan, randomization method, masking procedures, or model used for the endpoint. It also does not report a multiplicity approach. The listed secondary outcome, FEV1 (Spirometry) Change, has no result in the registry record. These gaps limit evaluation of analysis choices and interpretation across outcomes.

The study is described as a relatively short study, and the primary endpoint concerns a physiological measure assessed after 4 weeks of treatment. The registry does not report longer-term follow-up results. The safety summary gives participant counts for serious and other adverse events, but does not provide event descriptions for the other adverse events, severity, treatment relatedness, or a reported death count.

These limitations concern what can be concluded from the registry record; they do not establish that a particular analysis or procedure was absent from the underlying study. Unreported details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Hypertonic Saline on Mucus Clearance in Children Ages 5-12 With Cystic Fibrosis — NCT01031706.
• Registry record last updated 2017-03-03; status last verified 2014-03.
• Results first posted 2014-06-30.
• 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

This completed randomized, quadruple-masked, parallel-group study enrolled 23 children with cystic fibrosis and compared hypertonic saline with placebo. The primary endpoint was change in MCC90, measured from baseline to after completion of the 4 week treatment period, with the end measurement taken 8-12 hours after the final dose.

The posted mean changes were 2.77 percent clearance for hypertonic saline, based on 12 participants, and -2.35 percent clearance for placebo, based on 8 participants. Their standard errors were 0.98 and 1.82, respectively. The registry marks the two-arm comparison as missing or not estimable, so no comparative inferential result is available.

The registry lists FEV1 (Spirometry) Change as a secondary outcome but does not report its result. Serious adverse event counts were 0 in each group; other adverse event counts were 11 among 14 at risk and 9 among 9 at risk. The record does not report deaths. Missing outcome data, the full analysis plan, and the trial’s sample-size justification are not reported in the registry record.