Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study (NCT06350461), a randomized na study. The primary outcome is Absolute Change in FEV1 % Predicted From Week 0 to Week 6.

2. Clinical Question

The study addresses whether a chronic inhaled therapy can be stopped in the context of highly effective CFTR modulator treatment. The registry describes hypertonic saline as a therapy used to support mucus clearance and lung function, and frames the sub-study around whether stopping it changes lung function compared with continuing it. The posted primary outcome measures that question using FEV1 % predicted over the stated six-week period.

The comparison is about assignment to the two strategies, not a general claim about all people with cystic fibrosis, all CFTR modulators, or longer-term outcomes. The registry record identifies the condition as cystic fibrosis and the treatment strategies, but does not report further eligibility criteria in the information summarized for this analysis. It also does not report a non-inferiority margin or other threshold defining an acceptable change. That distinction matters when interpreting the sponsor’s non-inferiority analysis: the question and endpoint are clear, but the margin needed to judge the criterion is not reported in the registry record.

3. Trial Design

This is a randomized, parallel-group study with no masking. Participants were assigned to discontinue or continue hypertonic saline; the registry lists both strategies as interventions. The trial is marked completed and records enrollment of 370. Its phase is listed as NA. The study is a SIMPLIFY sub-study of a master protocol examining discontinuation of chronic therapies in people with cystic fibrosis receiving highly effective CFTR modulator therapy.

The primary endpoint is the absolute change in FEV1 % predicted from Week 0 to Week 6. The primary population is identified as the Per Protocol Population. The arm-level summaries used in the unadjusted recalculation report 133 participants in the discontinuation group and 140 in the continuation group. These endpoint analysis counts should not be confused with the overall enrollment or with the numbers reported in the safety record. The registry record does not report the reason for differences among these populations or analysis counts.

The record lists secondary outcomes covering lung clearance index, respiratory symptoms measured with CRISS and the CFQ-R respiratory domain, additional FEV1 % predicted changes, acute antibiotic initiation, hospitalization, and pulmonary exacerbations. The secondary outcome timeframes vary, including assessments from Week 0 to Week 6 and a separate FEV1 interval from Week -2 to Week 0. The trial is open-label, so participants and study personnel were not masked according to the masking field. Details such as the randomization procedure, allocation concealment, protocol deviations, and how missing measurements were handled 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

Analysis population for the primary outcome, as defined in the registry: Per Protocol Population

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: Primary analyses were done on the per-protocol (PP) population.

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change in FEV1 % Predicted From Week 0 to Week 6, measured over Week 0 to Week 6.

The primary endpoint is the absolute change in FEV1 % predicted from Week 0 to Week 6. FEV1 is forced expiratory volume in one second; expressing it as percent predicted places a measured value in relation to a predicted reference value. The endpoint is a continuous measure, and the posted arm summaries report means and standard deviations. The registry defines the primary comparison as the difference between the study arms in their absolute change over the specified interval.

Change over time focuses the comparison on movement during the study period rather than on a single follow-up measurement alone. FEV1 % predicted is used as a measure of lung function, consistent with the registry’s stated purpose of assessing whether discontinuing hypertonic saline is associated with a change in lung function while participants continue CFTR modulator therapy. A group mean describes the average change, while the spread describes how variable individual changes were within a group. Neither quantity alone describes every participant’s experience.

The endpoint does not directly measure all aspects of respiratory health, treatment burden, or longer-term outcomes. Other outcomes in the registry address respiratory symptoms and clinical events, but the primary analysis is specifically the change in FEV1 % predicted over Week 0 to Week 6. The registry record does not report a threshold for a clinically important change or a non-inferiority margin, so the result cannot be judged against such a threshold from the posted information alone.

7. Results Posted in the Registry

• HS-Continue: mean 0.10 versus -0.20 on control; difference 0.30 (95% CI -0.62 to 1.22), standardized effect d = 0.08; z-test p = 0.523.

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.

Absolute Change in LCI 2.5 From Baseline to Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • HS-Continue: mean 0.10 versus 0.10 on control; difference 0.00 (95% CI -0.37 to 0.37), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between HS-Continue and the control. The interval gives the range of effects that remain compatible with the data.

Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • HS-Continue: mean 0.20 versus -1.40 on control; difference 1.60 (95% CI -0.88 to 4.08), standardized effect d = 0.15; z-test p = 0.205.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between HS-Continue and the control. The interval gives the range of effects that remain compatible with the data.

Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • HS-Continue: mean 0.50 versus 0.70 on control; difference -0.20 (95% CI -2.14 to 1.74), standardized effect d = -0.02; z-test p = 0.840.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between HS-Continue and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the assessment beyond the primary lung-function measure. They include lung clearance index, respiratory symptoms assessed by CRISS and the CFQ-R respiratory domain, FEV1 changes in another interval, and event outcomes involving acute antibiotics, hospitalization, and pulmonary exacerbations. The registry indicates that 11 secondary outcomes were posted. The continuous secondary comparisons available in the posted summaries generally have estimates near zero relative to their uncertainty; their reported intervals include zero. That overall pattern does not establish that every secondary outcome is unchanged, nor does it resolve the primary analysis discrepancy.

These outcomes are relevant as complementary measures: respiratory symptoms and lung clearance provide perspectives distinct from FEV1, while antibiotic initiation, hospitalization, and exacerbations concern clinical events. They do not replace the primary endpoint, and each addresses a different aspect of the study question. The registry record does not give enough information to assess the completeness or analysis of every listed outcome from the summaries.

Secondary findings carry less weight when many outcomes are examined without a reported approach to multiplicity. Testing multiple outcomes can increase the chance of at least one apparently notable result arising by chance. The registry record does not report a multiplicity adjustment or a hierarchy governing secondary comparisons. Secondary results should therefore be treated as supportive or exploratory unless a prespecified analysis plan establishes otherwise. The lack of reported multiplicity details also means that individual secondary p-values should not be interpreted as if they were the sole confirmatory test.

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

• Absolute Change in LCI 2.5 From Baseline to Week 6
• Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6
• Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6
• Absolute Change in FEV1 % Predicted From Week -2 to Week 0
• Absolute Change in FEV1 % Predicted From Week 0 to Week 2
• Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6
• Number and Percent of Participants Hospitalized From Week 0 to Week 6
• Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, so the posted arm summaries use a mean and standard deviation. A mean is the arithmetic average of the observed changes in an arm. A standard deviation describes how dispersed those changes are around the mean; a larger standard deviation indicates greater variation among the observations. These summaries make it possible to describe the arms and to perform a simple unadjusted comparison, but they do not reproduce an analysis that uses participant-level data, covariate adjustment, or a different outcome summary.

What does the recalculated comparison represent?

The recalculated estimate is the difference between the posted arm means, expressed in the direction continuation minus discontinuation. It is an unadjusted comparison based on the posted summary statistics, not the sponsor’s reported analysis. The estimated difference is 0.3. Its 95% confidence interval runs from -0.622 to 1.221. Because this interval includes zero, values compatible with the data include a difference in either direction as well as no difference. The interval is not a probability statement that the true value lies inside it; under the usual frequentist interpretation, the method would cover the true parameter in 95% of repeated samples when its assumptions hold.

The unadjusted p-value of 0.523 describes how unusual a result at least as inconsistent with a zero-difference model would be under the test’s assumptions, if that model were true. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. A non-small p-value does not demonstrate equivalence. Equivalence or non-inferiority requires a prespecified margin and a suitable analysis; the margin is not reported in the registry record.

Why are the posted analyses not interchangeable?

The sponsor’s reported analysis is labeled ANOVA and is described as a median difference in final values. Its reported estimate is -0.324, its 95% confidence interval is -1.3 to 0.6, and its p-value is < 0.001 under a non-inferiority analysis label. The recalculation instead compares arm means of absolute change. A comparison of mean changes and an analysis of final values or medians need not produce the same estimate or inferential result. The discrepancy flagged in the record is therefore important rather than a rounding detail. The sponsor’s own analysis takes precedence; the summary-statistic recalculation serves only as a transparent, unadjusted cross-check.

ANOVA is a general method for comparing group outcomes under a model. The registry record does not provide enough detail to determine the exact model specification, treatment of baseline values, covariates, or standard-error calculation for the reported analysis. It also does not provide the non-inferiority margin. These omissions prevent a full audit of the sponsor-reported result from the registry entry alone.

What does a standard deviation tell the reader?

Standard deviations describe individual variability, whereas confidence intervals describe uncertainty in an estimated group-level quantity. These are related but different concepts. A group can have substantial participant-to-participant variation while the uncertainty in its mean difference is narrower, particularly when the analysis includes more observations. Conversely, a small estimated difference can remain uncertain when the data are variable or limited. The spread values in the arm summaries should not be read as confidence limits for the mean.

Some outcomes in the record are continuous and others are counts or percentages of participants with events. A mean-difference method is suited to a continuous measure under its assumptions; event outcomes call for methods appropriate to event counts or proportions. The posted primary recalculation is for the continuous FEV1 endpoint. The record does not report the statistical procedures used for all secondary or safety outcomes in the information.

General statistical interpretation also depends on design and data handling. Random assignment supports a comparison of assigned strategies, while the open-label design means masking was not used. Randomization details, adherence, protocol deviations, missing observations, and handling of incomplete measurements are not reported in the registry record. These details can affect how directly a particular analysis reflects the randomized comparison.

11. Confidence Intervals and Precision

The unadjusted recalculated mean difference for the primary endpoint is 0.3, with a 95% confidence interval from -0.622 to 1.221. The interval gives a range of values compatible with the observed summary data under the assumptions of the recalculation. Its inclusion of zero means the data are compatible with no difference in the arm means, while the values at either end also allow differences in either direction. This is uncertainty about the estimated group contrast, not a statement about the range of changes among individual participants.

The sponsor-reported primary analysis has a different estimate and interval: -0.324, with a 95% confidence interval from -1.3 to 0.6. Because the sponsor analysis and the recalculation use different reported summaries and do not agree, the two intervals should not be combined or treated as alternative versions of the same estimator. The sponsor’s own analysis takes precedence, while the recalculated interval illustrates the uncertainty around a simple unadjusted comparison of the posted arm means.

A confidence interval’s width reflects both the variability in the data and the amount of information available to estimate the quantity. A confidence interval that includes zero does not prove no effect, and it does not establish equivalence. To interpret precision against a clinically acceptable difference or a non-inferiority margin, that threshold must be specified; it is not reported in the registry record. Precision is also limited to the defined endpoint, population, and Week 0 to Week 6 timeframe. It should not be generalized to longer-term effects or outcomes not captured by FEV1 % predicted.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. For continuous outcomes, the entries are participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the planned number of participants per arm that would yield an 80% chance of detecting the specified effect under those assumptions if that effect were the true one. The 90% power column applies the same idea with a higher probability of detection, and therefore requires a larger planned sample under the stated method. These are hypothetical design calculations, not an assessment of the probability that this completed trial detected an effect.

The rows describe planning for 100%, 75%, and 50% of the observed effect. A smaller target effect is harder to distinguish from random variation, so the illustration requires more participants per arm as the assumed effect becomes smaller. This relationship is general to the stated planning framework, but the specific figures depend on the observed effect and the assumptions listed. The sample-size illustration is not observed power. It does not determine whether the trial’s result is valid, whether the estimate is clinically important, or whether the sponsor’s non-inferiority criterion was met. For non-inferiority planning, the relevant margin and design details would be needed, and these are not reported in the registry record.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.300; pooled standard deviation σ = 3.871.
2. n = 2 × (1.96 + 0.842)² × 3.871² / 0.300² = 2,613.5, rounded up to 2,614 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
delta <- 0.3                      # observed difference in means
sigma <- 3.87089356275392                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(6350461)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,614 (80% power), 3,499 (90% power)
 75% of observed effect: n per arm = 4,647 (80% power), 6,220 (90% power)
 50% of observed effect: n per arm = 10,454 (80% power), 13,995 (90% power)
power.t.test: 2614.4 
Simulated power at n = 2,614 per arm: 0.806 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 primary result is reported as an ANOVA analysis of median difference in final values: -0.324, with a 95% confidence interval from -1.3 to 0.6 and p < 0.001, labeled as a non-inferiority analysis. The unadjusted recalculation instead uses the posted means of absolute change and estimates continuation minus discontinuation as 0.3, with a 95% confidence interval from -0.622 to 1.221 and p = 0.523. These are not the same analysis or estimand, and the results differ.

The discrepancy is flagged in the registry record, so the sponsor’s own analysis takes precedence over the recalculation. The recalculation is a simple check using arm-level summary statistics, not a replication of the sponsor’s participant-level model. The registry record does not report enough detail to reconstruct the sponsor’s analysis, including its non-inferiority margin and full model specification. Consequently, the sponsor-reported label and p-value should not be treated as independently verified by the summary-statistic calculation, and the recalculated p-value should not be substituted for the sponsor’s analysis.

15. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome and numerous secondary outcomes, but multiplicity handling is not reported in the registry record. Multiplicity matters because interpreting many tests separately can make an apparently unusual result more likely to occur by chance somewhere among the set of analyses. An adjustment, a prespecified hierarchy, or a clearly defined distinction between confirmatory and exploratory outcomes can help readers understand how to interpret multiple tests. The registry entry does not state whether any such approach was used.

Missing-data methods are also not reported in the registry record. The primary outcome is assigned to the Per Protocol Population, but the entry does not explain how participants entered or remained in that population, how missing Week 0 or Week 6 measurements were handled, or whether other analysis populations were used. The arm summaries include endpoint-specific analysis counts, but those counts alone do not explain why measurements are absent or whether missingness could be related to outcome or treatment assignment.

The registry record does not report details about protocol deviations, adherence to assigned hypertonic saline strategies, imputation, sensitivity analyses, or a prespecified statistical analysis plan. These are relevant because a per-protocol analysis and an analysis based on all randomized participants can answer different questions when deviations or missing observations occur. The record also does not report the non-inferiority margin or the full sponsor model specification. As a result, the posted information is insufficient to independently assess the robustness of the non-inferiority conclusion or the influence of missing data and multiple testing.

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: abdominal pain (0.5%), suicidal ideation (0.5%), infective pulmonary exacerbation of cystic fibrosis (0.5%).

The registry reports serious adverse event figures separately for the discontinuation and continuation groups. In the discontinuation group, 184 were listed as at risk and 2 as affected; in the continuation group, 186 were listed as at risk and 1 as affected. Deaths are reported as 0 in each group. The record also lists serious event terms including abdominal pain, suicidal ideation, and infective pulmonary exacerbation of cystic fibrosis, each shown as 0.5%.

These are descriptive safety figures, not an adjusted comparison of risk. The registry entry does not report a statistical test for these events in the information. The other adverse event figures list 5 affected among 184 at risk in the discontinuation group and 10 affected among 186 at risk in the continuation group. Event counts should be interpreted with their reported denominators and the study’s follow-up context, rather than as proof that one strategy is safer. The trial’s primary result concerns FEV1 change, and the safety figures do not resolve that efficacy analysis or its discrepancy.

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

The posted results describe a randomized comparison of stopping versus continuing inhaled hypertonic saline among people with cystic fibrosis receiving highly effective CFTR modulator therapy. The primary endpoint captures the change in FEV1 % predicted from Week 0 to Week 6. The arm-level mean changes were close, and the simple unadjusted recalculation has an interval that includes zero. This indicates uncertainty about the difference in mean change under that calculation; it is not proof of no difference.

The registry’s sponsor-reported primary analysis is labeled non-inferiority and reports a different estimate, interval, and p-value. Since the recalculation and sponsor analysis differ, the sponsor’s own analysis takes precedence. The non-inferiority margin is not reported in the registry record, so the posted information does not permit independent evaluation of whether the reported interval satisfied the relevant criterion. Neither a non-significant unadjusted comparison nor a reported non-inferiority label alone should be translated into a claim of equivalence without the margin and analysis details.

The result is limited to the defined population, endpoint, and short study timeframe. It does not establish effects on longer-term lung function, all respiratory symptoms, or every clinical event. Secondary outcomes provide additional measures but should be interpreted cautiously because multiplicity handling is not reported. Safety counts are descriptive and do not establish comparative safety. The registry record also does not report missing-data methods or the complete statistical analysis plan, which limits a full assessment of bias and robustness.

Accordingly, the posted data are best read as a short-term, randomized comparison with an unresolved difference between the sponsor’s primary analysis and a simple summary-statistic recalculation. The record gives useful endpoint and arm summaries, but important inferential details needed to assess non-inferiority and analytic robustness are not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why the estimand and analysis method matter as much as the numerical result. A simple difference between arm means of change is not interchangeable with an analysis of final values or medians. Here, the unadjusted recalculation and the sponsor’s reported primary analysis differ in their estimates and p-values, and the record flags the discrepancy. Keeping the analyses distinct prevents a summary-statistic calculation from being mistaken for the sponsor’s model-based result.

The non-inferiority label also highlights the importance of a prespecified margin. A non-inferiority analysis asks whether a difference is sufficiently limited relative to an acceptable boundary; absence of a statistically significant superiority result is not the same question. Without the margin and full analysis details, readers cannot independently assess the non-inferiority claim from the registry record alone.

The study also demonstrates why confidence intervals, not p-values alone, are central to interpretation. The unadjusted interval describes a range of contrasts compatible with the data under its assumptions and includes zero, while not ruling out differences in either direction. Secondary measures and safety outcomes add context but bring additional interpretive issues, including multiplicity, endpoint-specific analysis counts, and missing-data handling. These details are not fully reported in the registry record.

For biostatisticians and clinical researchers, the central lesson is to distinguish the target question, population, outcome summary, analysis population, and inferential criterion. Those distinctions are essential for interpreting chronic-therapy discontinuation studies, where a result about a short-term lung-function measure should not be generalized beyond its stated scope.

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.

The registry record does not report the non-inferiority margin, so the sponsor’s non-inferiority result cannot be independently assessed against its decision boundary from the posted information. The sponsor analysis and simple unadjusted recalculation differ, and the full model specification is not reported. The primary outcome is defined for the Per Protocol Population, but the record does not explain its construction or provide details about other analysis populations.

Missing-data handling, protocol deviations, adherence, allocation concealment, and the randomization procedure are not reported in the registry record. The study is unmasked, as indicated by masking listed as none. The posted primary interval applies to the Week 0 to Week 6 outcome and cannot establish longer-term effects. The record does not report a clinically important threshold for the FEV1 measure.

The registry lists multiple secondary outcomes, but multiplicity procedures are not reported. Some secondary outcomes concern continuous measurements and others clinical events, and their analysis details are not given in the information summarized for this interpretation. Safety figures are descriptive; a statistical comparison or adjusted safety analysis is not reported. These limitations do not invalidate the posted results, but they restrict the conclusions that can be drawn from the registry record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study — NCT06350461.
• Registry record last updated 2024-10-01; status last verified 2024-05.
• Results first posted 2024-10-01.
• 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

This completed randomized, parallel-group, unmasked SIMPLIFY sub-study compares discontinuation with continuation of inhaled hypertonic saline in people with cystic fibrosis receiving highly effective CFTR modulator therapy. Enrollment is 370. The primary endpoint is absolute change in FEV1 % predicted from Week 0 to Week 6 in the Per Protocol Population.

The sponsor-reported primary result is labeled as a non-inferiority analysis, while an unadjusted recalculation from the posted arm means differs. The sponsor’s own analysis takes precedence, but the non-inferiority margin and full analysis details are not reported in the registry record. Secondary outcomes span lung function, symptoms, and clinical events. Multiplicity and missing-data methods are not reported, and safety figures are descriptive.