Deposition of Inhaled Prolastin in Cystic Fibrosis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Deposition of Inhaled Prolastin in Cystic Fibrosis Patients (NCT00486837), a randomized phase 2 study. The primary outcome is Change in Free Elastase in Induced Sputum From Baseline to Week 4.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 study of inhaled alpha1-proteinase inhibitor in people with cystic fibrosis. It compared two intended deposition sites: the bronchial region and the periphery of the lung. The brief study description says that AKITA nebulizer settings could target the drug to the deep lung or upper airways, with one-to-one randomization. The record reports no masking; participants and study personnel therefore were not described as masked in the registry record. Whether any outcome assessors were masked is not reported in the registry record.

The recorded enrollment was 72. The trial is marked completed, with a recorded start of 2003-12 and primary completion of 2004-06. These are registry dates, not a description of how long each participant was followed. The listed regimen in both arms was 25 mg in the lungs, one inhalation per day over 4 weeks. Both groups received the same named intervention; the intended deposition region was the key design contrast.

The primary outcome analysis used a modified intent-to-treat population. That population included randomized participants who received any amount of study medication and had a baseline and at least one post-baseline free-elastase evaluation. The reported primary arm sizes are 28 for peripheral deposition and 24 for bronchial deposition. Those outcome-specific numbers do not explain the relationship between enrollment, treatment receipt, and inclusion in the analysis. Participant flow, reasons for exclusion, adherence, and handling of missing measurements are not reported in the registry record.

The registry lists five secondary outcomes covering sputum AAT activity, immunoglobulin G fragments, bacterial load, Pseudomonas load, and neutrophil number. Numerical results are posted for three of these outcomes; results for the other listed outcomes are not reported in the registry record. The trial's original sample-size justification and detailed statistical analysis plan 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.

Before assignment: Subjects inhaled saline once daily for 2 weeks during the Run-in Period.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat Population (mITT) was all randomized subjects who received any amount of study medication and had at least one evaluation of the primary efficacy variable (free elastase in induced sputum) post baseline and at baseline (Visit 2).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Free Elastase in Induced Sputum From Baseline to Week 4, measured over Baseline vs Week 4.

The primary endpoint was change in free elastase in induced sputum from baseline to Week 4, measured in ug/mL. The registry describes the outcome as a mean with standard deviation and identifies the analysis population as modified intent-to-treat. Free elastase is relevant to the stated study objective because the trial aimed to assess whether inhaled AAT could inhibit elastase activity, and whether that response differed according to the lung region targeted for deposition.

A change score expresses how the measured outcome at follow-up differs from its baseline value for the analyzed participants. Comparing mean changes between randomized groups focuses the analysis on the difference associated with the assigned deposition strategies during the stated treatment period. It is a continuous outcome, so its summary includes both a group mean and a measure of variability. The standard deviation describes how spread out individual measurements are around the group mean; it is not the same as the uncertainty in the estimated group mean or in the between-group contrast.

The registry record does not report a clinically meaningful threshold for free elastase change, or enough detail to determine how measurements below an assay limit, if any, were handled. The endpoint can describe the measured biochemical response, but the registry information alone does not establish how a change should be interpreted for symptoms, lung function, or other patient-important outcomes.

7. Results Posted in the Registry

• Bronchial Deposition: mean 6.11 versus -7.42 on control; difference 13.53 (95% CI -3.20 to 30.26), standardized effect d = 0.44; z-test p = 0.113.

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.

Change in Alpha-1-anti-trypsin (A1AT) Activity in Induced Sputum From Baseline at Week 4

• 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:
  • Group 2: mean 6,469 versus 16,741 on control; difference -10,272 (95% CI -25,499 to 4,955), standardized effect d = -0.38; z-test p = 0.186.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2 and the control. The interval gives the range of effects that remain compatible with the data.

Change in Total Immunoglobulin G (IgG) Fragments in Induced Sputum From Baseline at Week 4

• 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:
  • Group 2: mean -0.48 versus 0.01 on control; difference -0.48 (95% CI -1.22 to 0.25), standardized effect d = -0.36; z-test p = 0.196.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2 and the control. The interval gives the range of effects that remain compatible with the data.

Change in Total Bacterial Load in Induced Sputum From Baseline to Week 4

• 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:
  • Group 2: mean 5,021,353 versus 22,673,276 on control; difference -17,651,923 (95% CI -130,014,828 to 94,710,983), standardized effect d = -0.09; z-test p = 0.758.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2 and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes broaden the focus from free elastase to AAT activity, immunoglobulin G fragments, total bacterial load, Pseudomonas load, and neutrophil number in induced sputum. Numerical summary results and simple comparisons are available for AAT activity, immunoglobulin G fragments, and total bacterial load. The registry lists Pseudomonas load and neutrophil number as secondary outcomes, but their numerical results are not reported in the registry record.

For the secondary outcomes with numerical comparisons, the posted re-calculated intervals include zero. This means the available summary-based contrasts do not precisely distinguish a difference from no difference. The pattern should not be read as proof that the deposition strategies are the same, nor as a definitive result for all sputum measures. The primary result is also uncertain, so the secondary findings do not resolve the uncertainty in the primary comparison or establish a broader biological pattern.

These secondary outcomes can add context about different aspects of sputum biology, but they do not replace the primary endpoint. They were not the primary question, and no sponsor-reported analyses are listed for them. The registry record does not report a multiplicity adjustment or a prespecified hierarchy among secondary outcomes. When several outcomes are examined, unadjusted tests can produce apparently notable results by chance even when there is no true effect. That consideration makes isolated secondary signals less persuasive unless supported by an appropriate analysis plan, consistent evidence, and replication.

The registry does not provide enough information to assess the full secondary-outcome evidence base: two listed outcomes lack posted numerical results, and analysis details for the available outcomes are not given. The overall secondary pattern is therefore best treated as exploratory and incomplete, rather than as independent confirmation of the primary finding or a basis for claims about clinical effects.

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

• Change in Alpha-1-anti-trypsin (A1AT) Activity in Induced Sputum From Baseline at Week 4
• Change in Total Immunoglobulin G (IgG) Fragments in Induced Sputum From Baseline at Week 4
• Change in Total Bacterial Load in Induced Sputum From Baseline to Week 4
• Change in Pseudomonas Load in Induced Sputum From Baseline at Week 4
• Change in Neutrophil Number in Induced Sputum From Baseline at Week 4

9. Statistical Interpretation

10. Statistical Methods Explained

The trial is described as randomized, parallel group, and unmasked. Random allocation is intended to make treatment groups comparable on average, including with respect to factors that may influence an outcome. In this study, the assigned strategies differed in the intended lung deposition region. Randomization does not guarantee that the realized groups are identical, especially in a trial of this size, and it does not remove uncertainty from an outcome estimate.

What does the mean difference represent?

The reported arm summaries give a mean change for each deposition group. The re-calculated mean difference is the bronchial-deposition mean minus the peripheral-deposition mean. Its positive value of 13.53 ug/mL indicates that the posted mean change was numerically higher in the bronchial group. This direction alone does not establish that the difference is important or favorable; interpretation depends on the outcome's meaning, uncertainty, and a clinically meaningful threshold. No such threshold is reported in the registry record.

The arm standard deviations, 29.96 and 31.3, describe variability among the analyzed observations within each group. These values are much larger in scale than the difference in group means, which is consistent with substantial variation relative to the estimated contrast. Standard deviations are descriptive; they do not directly show how uncertain the mean difference is. The uncertainty of a contrast also depends on the analyzed group sizes and the statistical method.

What does the unadjusted re-calculation do?

The posted re-calculation is a simple comparison of the group means and uses the reported summary statistics. It does not adjust for baseline values or other covariates. The estimated difference is 13.53 ug/mL, with an interval from -3.202 to 30.26, and an unadjusted p-value of 0.113. This calculation is useful for describing the contrast implicit in the posted means, but it is not a substitute for a sponsor-reported model when the latter is the designated analysis. It also does not reconstruct participant-level analyses or account for features that cannot be recovered from summary data.

Why is ANCOVA a different method?

ANCOVA is a regression approach that compares groups while accounting for one or more covariates. In general, such adjustment can improve precision when the covariates are related to the outcome and can account for baseline differences. That is a general explanation, not a claim about which variables were included in this trial's model. The registry identifies ANCOVA and reports p = 0.197, but the covariates, model specification, adjusted estimate, and interval are not reported in the registry record. It is therefore not possible to reproduce or fully interpret the sponsor's model from the posted information.

A p-value describes how incompatible the observed data are with a specified null hypothesis under the statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The reported ANCOVA p-value and unadjusted p-value are both above the conventional 0.05 level listed among the planning assumptions, but that fact alone does not establish no effect. The interval for the unadjusted contrast is more informative about plausible directions and magnitudes than a threshold-based interpretation of the p-value alone.

How should the analysis population be understood?

The modified intent-to-treat definition requires randomization, receipt of any amount of study medication, and both a baseline and at least one post-baseline evaluation of free elastase. This is narrower than an analysis that includes all randomized participants, because participants without the specified treatment exposure or outcome measurements do not meet the stated definition. The record gives primary outcome group sizes of 28 and 24 but does not provide a participant disposition, reasons for missingness, or imputation method. The effects of exclusions or missing data therefore cannot be assessed from the registry record.

The secondary outcomes are also continuous measures, and the posted summaries use means and standard deviations. The simple comparison estimates and intervals are re-calculations from those posted summaries rather than reported model results. No sponsor-reported analyses are listed for those secondary measures. Such re-calculations provide a transparent descriptive comparison but cannot account for unreported modeling choices or missing-data procedures.

Why can over-dispersion matter?

As a general statistical point, over-dispersion means that observed variability is greater than a model's assumptions would predict. When that happens, methods that assume less variability can make uncertainty look too small and evidence look stronger than it is. The primary outcome is analyzed as a continuous measure with a standard deviation, not as a count outcome in the registry record. The record does not identify an over-dispersion assessment or a model for the primary outcome beyond naming ANCOVA, so over-dispersion should not be inferred as a specific issue in this analysis.

The registry provides neither a detailed statistical analysis plan nor the trial's original sample-size assumptions. The separate planning illustrations use the assumptions explicitly stated for those calculations and should not be mistaken for the study's design rationale. They do not represent observed power or prove that the completed study was adequately or inadequately sized.

11. Confidence Intervals and Precision

The interval for the unadjusted primary mean difference extends from -3.202 to 30.26 ug/mL. Because it includes zero, the data are compatible with no mean difference under this calculation. They are also compatible with a negative difference or a positive difference, so the direction and magnitude are not pinned down precisely. In practical terms, the estimate does not distinguish a small contrast from a larger one with confidence.

A confidence interval is a range produced by a statistical procedure to express uncertainty around an estimate. In general, a wider interval indicates less precision, while a narrower interval indicates more precision, given the same method and scale. An interval is not a range containing a fixed proportion of individual participant outcomes, and it does not assign probabilities to each possible true value. The interval posted for the re-calculated contrast is based on summary statistics; the registry record does not identify its confidence level. The sponsor-reported ANCOVA analysis lists a 95% confidence level, but its interval bounds are not reported.

The observed group standard deviations are 29.96 for peripheral deposition and 31.3 for bronchial deposition. They indicate considerable spread in individual changes relative to the reported mean difference, though standard deviations and confidence intervals describe different sources of variation. The analyzed group sizes are 28 and 24, and uncertainty in the group contrast reflects both the spread of outcomes and the available observations.

The sponsor's ANCOVA result supplies a p-value but no effect estimate or interval. A p-value alone cannot convey the range of effect sizes consistent with the data, so the precision of the adjusted estimate cannot be evaluated from the registry entry. Neither the adjusted test nor the unadjusted interval establishes equivalence, and no equivalence margin is reported in the registry record.

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 planning illustrations give participants per arm, not a total across arms. They use the observed primary mean difference as a starting point and show planning estimates for detecting the full observed effect, 75% of that effect, or 50% of that effect. Under the full observed-effect scenario, the estimates are 81 participants per arm for 80% power and 108 participants per arm for 90% power. For 75% of the observed effect, they are 143 and 191 participants per arm. For 50% of the observed effect, they are 321 and 430 participants per arm.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The 80% power column describes the planned chance of detecting the specified effect under those assumptions if that effect is real; the 90% column uses a higher target chance of detection. These are planning concepts conditional on the assumptions and the chosen effect, not guarantees about what a future study will find. Smaller effects require more participants to detect under the same assumptions, which is why the estimates increase as the effect fraction decreases.

These figures are planning illustrations based on the observed effect, not observed power and not the trial's original design justification. The original sample-size assumptions are not reported in the registry record. They should therefore be read as hypothetical planning quantities, not as evidence that the completed trial was or was not adequately powered. The plotted planning values express the same relationship between effect size and required participants; they do not add information about the trial's actual enrollment or outcome precision.

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 = 13.530; pooled standard deviation σ = 30.584.
2. n = 2 × (1.96 + 0.842)² × 30.584² / 13.530² = 80.2, rounded up to 81 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 <- 13.53                      # observed difference in means
sigma <- 30.5836927789958                     # 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(486837)
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 = 81 (80% power), 108 (90% power)
 75% of observed effect: n per arm = 143 (80% power), 191 (90% power)
 50% of observed effect: n per arm = 321 (80% power), 430 (90% power)
power.t.test: 81.2 
Simulated power at n = 81 per arm: 0.798 (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 registry reports a sponsor ANCOVA analysis with p = 0.197 for the primary comparison. It does not provide the adjusted mean difference, confidence interval, covariates, or fuller model specification. Consequently, the magnitude and precision of the sponsor's adjusted estimate cannot be described from the registry record.

The simple re-calculation from the posted arm means gives a bronchial-minus-peripheral difference of 13.53 ug/mL, an interval from -3.202 to 30.26, and an unadjusted p-value of 0.113. It is an unadjusted calculation from summary statistics, not a reconstruction of ANCOVA. The difference between p = 0.197 and p = 0.113 does not by itself indicate an error: the methods are not identical, and the model details needed to understand the contrast are absent.

Both reported p-values are above 0.05, but neither should be treated as proof of no difference. The unadjusted interval shows uncertainty in the simple contrast, while the sponsor result gives a model-based test without the associated effect estimate and interval. The record does not flag a discrepancy between the posted results and the re-calculation. The sponsor analysis is the registry's reported analysis; the re-calculation is best read as a complementary descriptive check, not as a replacement for information that the registry does not report.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and five secondary outcomes. It does not report whether the statistical analysis plan controlled the overall false-positive risk across multiple outcomes, used a testing hierarchy, or designated any secondary analyses as exploratory. No multiplicity adjustment is reported for the secondary comparisons. When several outcomes are tested, the chance of at least one apparently unusual result can increase; this is a general statistical concern, not a claim that a particular false-positive result occurred in this trial.

The posted secondary comparisons are unadjusted re-calculations from summary statistics, and no sponsor-reported analyses are listed for them. Their p-values should therefore be interpreted cautiously and in the context of the number of outcomes examined. Results that are not adjusted for multiplicity can still be informative, but they carry less confirmatory weight than a clearly prespecified primary analysis with a documented strategy for secondary testing. The statistical plan and any multiplicity procedure are not reported in the registry record.

The primary analysis population is defined as randomized participants who received any amount of study medication and had baseline and at least one post-baseline evaluation of free elastase. This definition is reported, but the registry does not provide the numbers excluded for each reason, participant-level missingness, or a flow account connecting enrollment to the primary analysis groups. It also does not state whether missing outcomes were imputed, whether a particular missing-data assumption was used, or whether sensitivity analyses were conducted.

These omissions matter because the observed analysis may depend on who had usable measurements. If outcome availability is related to treatment assignment or to the outcome itself, a complete-case comparison can be affected. That is a general limitation of missing-data analyses; the registry record does not establish that such a bias occurred. It also does not describe an analysis of all randomized participants or provide enough detail to judge the robustness of the modified intent-to-treat result.

The original sample-size justification, interim-analysis procedures, and detailed statistical analysis plan are not reported in the registry record. Their absence prevents assessment of whether the analysis methods, outcome hierarchy, and sample-size target were set in advance.

16. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero participants with serious adverse events in each safety group. The serious-event at-risk figures are 37 for peripheral deposition and 35 for bronchial deposition. No serious-event terms are listed. Deaths are not reported in the registry record.

For other adverse events, the record lists 10 affected participants among 37 at risk in the peripheral group and 13 among 35 at risk in the bronchial group. These are descriptive counts, not a randomized comparison with an uncertainty estimate. The registry entry does not give event types, severity breakdowns, timing, exposure-adjusted rates, or details about how events were collected. It also does not explain why the safety at-risk figures differ from the primary outcome analysis group sizes.

Zero reported serious events should be read as the registry's recorded count for these groups, not as proof that serious harm is impossible or that the intervention is safe in every setting. The available safety information is limited to the posted counts and does not support a comprehensive safety assessment.

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

The primary result is an estimate of how mean free-elastase change in induced sputum differed between two inhaled deposition strategies during the stated 4-week regimen. The unadjusted estimate is 13.53 ug/mL in the direction of a higher mean change for bronchial than peripheral deposition. Its interval, from -3.202 to 30.26, spans zero, and the unadjusted p-value is 0.113. The sponsor-reported ANCOVA test gives p = 0.197, but the registry does not report its adjusted effect estimate or interval.

These results do not establish that one deposition strategy is superior, and they do not establish that the strategies are equivalent. A lack of conventional statistical evidence for a difference is not proof that no difference exists. The confidence interval for the unadjusted estimate includes effects in either direction, and the registry does not report an equivalence margin or a clinically meaningful change threshold.

The outcome is a sputum measure of free elastase, not a direct measure of symptoms, lung function, exacerbations, quality of life, or survival. Although the study summary describes elastase inhibition as the biological focus, the posted endpoint alone cannot establish the effect of treatment on broader health outcomes. The results also do not establish the drug's effects compared with no treatment, because the two groups received the same named intervention and differed in intended deposition site.

Interpretation is limited to the modified intent-to-treat population and the recorded treatment period. The registry does not provide sufficient participant-flow or missing-data information to determine how the analyzed population relates to all enrolled participants. The result should therefore be understood as an uncertain comparison of measured sputum changes in this study, rather than a definitive conclusion about clinical benefit or harm.

18. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can be designed around a delivery question rather than a drug-versus-no-drug contrast. Both groups received inhaled alpha1-proteinase inhibitor at the same stated dose and frequency, while the intended deposition site differed. That design focuses the statistical comparison on the delivery strategy, and the primary outcome aligns with the stated objective of measuring elastase inhibition in sputum.

It also shows why an estimate and its uncertainty should be read together. The mean difference gives a direction and scale, while the interval indicates how much uncertainty remains. A p-value by itself does not tell readers whether an effect is large, small, precise, or clinically important. Here, the unadjusted interval crosses zero and extends to a range of possible differences; the sponsor's model-based p-value is reported without the adjusted estimate or interval needed for a fuller interpretation.

The record also highlights the importance of defining the analysis population and documenting participant flow. The modified intent-to-treat definition is explicit, but the record does not show how enrollment translated into the analyzed groups or how missing outcome data were handled. Such information is essential for judging the credibility and generalizability of a trial result.

Finally, multiple secondary outcomes can offer biological context while increasing the need for a prespecified interpretation strategy. With no reported multiplicity procedure and numerical results absent for some listed outcomes, secondary findings cannot serve as strong independent confirmation. These are broadly useful statistical lessons from a study whose central result remains uncertain.

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 leaves important design and analysis details unspecified. It identifies randomization but does not describe the sequence-generation method, allocation concealment, or operational details of the deposition procedures. The study is marked unmasked. Whether outcome assessors or laboratory personnel were masked is not reported in the registry record, and the potential for measurement-related bias cannot be evaluated from the entry.

The reported enrollment is 72, while the primary modified intent-to-treat groups contain 28 and 24 participants. The record defines eligibility for that analysis but does not provide a participant-flow account, reasons for missing measurements, or the number excluded at each stage. The difference between enrollment and the outcome-specific groups therefore cannot be explained from the registry information alone. Missing-data methods and sensitivity analyses are also not reported.

The sponsor's ANCOVA result is reported as a p-value without an effect estimate, interval, or covariate list. This makes the adjusted result difficult to assess or reproduce. The unadjusted re-calculation is informative but cannot recover participant-level information or account for unspecified model choices. The original sample-size justification and detailed statistical analysis plan are not reported.

The registry provides numerical results for only some listed secondary outcomes and does not report a multiplicity strategy. The outcome is a sputum biomarker, and a clinically meaningful threshold is not given. Safety information is limited to affected-participant counts, with no event descriptions or deaths reported. Together, these omissions restrict conclusions about the precision, robustness, clinical relevance, and broader safety implications of the findings.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Deposition of Inhaled Prolastin in Cystic Fibrosis Patients — NCT00486837.
• Registry record last updated 2014-08-21; status last verified 2014-08.
• Results first posted 2014-08-21.
• 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

The registry describes a completed, randomized, unmasked, parallel-group phase 2 study of inhaled alpha1-proteinase inhibitor in people with cystic fibrosis. It compared intended bronchial and peripheral lung deposition, with 25 mg in the lungs, one inhalation per day over 4 weeks in each group. The recorded enrollment was 72.

The primary outcome was change in free elastase in induced sputum from baseline to Week 4 in a modified intent-to-treat population. The unadjusted mean difference was 13.53 ug/mL, with an interval from -3.202 to 30.26 and p = 0.113. The sponsor-reported ANCOVA analysis gives p = 0.197 but does not include an adjusted estimate or interval in the registry record.

The available results do not establish a clear difference or equivalence between deposition strategies. Missing-data details, the original sample-size justification, and a detailed analysis plan are not reported in the registry record. Secondary and safety findings are limited by incomplete reporting and should be interpreted cautiously.