Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (NCT00712166), a randomized phase 3 study. The primary outcome is Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28.

2. Clinical Question

The question concerns a patient-reported measure of respiratory symptoms over the period from Day 0 to Day 28. The CFQ-R RSS asks about symptoms such as coughing, congestion, and wheezing. Its scores range from 0 to 100, with higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning. The study also recorded changes in this scale at other time points and assessed physical functioning, antibiotic use, hospitalization, sputum Pseudomonas aeruginosa, and FEV1. The registry record lists these additional outcomes, but numerical results for several of them are not reported in the registry record.

3. Trial Design

This was a Phase 3 randomized, placebo-controlled, parallel-group trial described in its official title as double-blind, multicenter, and multinational. The registry reports quadruple masking. The meaning of each masked role is not reported in the registry record. The study status is completed, with an enrollment of 160. Its start is recorded as 2008-05 and primary completion as 2009-06.

The comparison was AZLI 75 mg three times daily against placebo three times daily. The registry's primary outcome analysis describes an intent-to-treat population as participants who received at least part of one dose of AZLI or placebo. The reported arm-level outcome counts are 81.0 for placebo and 76.0 for AZLI; these are the counts associated with the primary outcome results and should not be read as a breakdown of all enrolled participants or as a statement about the original allocation.

The primary outcome was change from baseline in CFQ-R RSS score at Day 28. Baseline CFQ-R RSS and age group (<18 versus >=18 years) were included as covariates in the analysis. The planned study duration was described as a 28-day course. Specific details of the randomization procedure, allocation concealment, site count, and original sample-size justification are not reported in the registry record. Nor does the registry record describe an interim analysis plan.

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: Planned trial size was approximately 140 participants randomized in 1:1 ratio to aztreonam for inhalation solution (AZLI) three times daily (TID) or placebo TID. 160 participants were randomized, 157 received blinded study drug (76 AZLI; 81 placebo). One participant who was randomized and treated with study drug discontinued the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis on intent-to-treat (ITT) population (received at least part of 1 dose of AZLI/placebo). Missing baseline data not imputed. Missing post-baseline data imputed with worst-case value for participants who withdrew due to an adverse event (AE)/study drug intolerance. Imputation for other missing data was last observation carried forward (LOCF).

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 From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28, measured over Day 0 to Day 28.

The primary endpoint is change from baseline in the CFQ-R Respiratory Symptoms Scale score from Day 0 to Day 28. The CFQ-R is a validated patient-reported measure of health-related quality of life for children and adults with cystic fibrosis. Its respiratory symptom scale captures experiences including coughing, congestion, and wheezing. Scores range from 0 to 100; higher scores indicate fewer symptoms, higher health-related quality of life, or better functioning.

A change score compares the participant's score after baseline with the baseline score. The endpoint therefore focuses on how reported respiratory symptoms changed during the study period, rather than on a single score alone. A positive change is in the direction of fewer symptoms according to the scale's stated interpretation.

Patient-reported outcomes can add information about how participants experience symptoms, which may not be fully represented by physiological measures. The CFQ-R RSS was assessed at Days 0, 14, 28, and 42, while Day 28 was designated as the primary time point. The analysis adjusted for baseline RSS and age group. The registry record describes the primary estimate as a least-squares mean and reports the comparison using an ANCOVA analysis of final values.

7. Results Posted in the Registry

• AZLI 75 mg Three Times Daily (TID): mean 3.22 versus 1.41 on control; difference 1.81 (95% CI -2.83 to 6.45), standardized effect d = 0.12; z-test p = 0.445.

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 From Baseline in CFQ-R RSS Score at Day 14

• 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 errors.
• Result:
  • AZLI 75 mg Three Times Daily (TID): mean 3.65 versus 0.28 on control; difference 3.37 (95% CI -1.05 to 7.79), standardized effect d = 0.24; z-test p = 0.135.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZLI 75 mg Three Times Daily (TID) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in CFQ-R RSS Score at Day 42

• 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 errors.
• Result:
  • AZLI 75 mg Three Times Daily (TID): mean 3.02 versus 2.91 on control; difference 0.11 (95% CI -4.56 to 4.78), standardized effect d = 0.01; z-test p = 0.963.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZLI 75 mg Three Times Daily (TID) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in CFQ-R Physical Functioning Domain Score

• 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 errors.
• Result:
  • AZLI 75 mg Three Times Daily (TID): mean 1.79 versus -0.69 on control; difference 2.48 (95% CI -1.82 to 6.78), standardized effect d = 0.18; z-test p = 0.258.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZLI 75 mg Three Times Daily (TID) and the control. The interval gives the range of effects that remain compatible with the data.

The registry reports numerical results for three secondary continuous outcomes: CFQ-R RSS change at Day 14, CFQ-R RSS change at Day 42, and change in the physical functioning domain score. Across these posted measures, the AZLI arm estimates are in the positive direction relative to placebo. The corresponding reported confidence intervals include zero, so these results do not provide a precise separation between groups.

This broad pattern is consistent with the uncertainty in the primary Day 28 result: estimates can point in a direction while remaining compatible with no between-group difference. The different time points and domains address related but distinct questions, and should not be treated as independent confirmations of the same effect. The registry also lists secondary outcomes concerning use of additional antipseudomonal antibiotics, hospitalization, sputum Pseudomonas aeruginosa, and relative FEV1 change; numerical results for these outcomes are not reported in the registry record.

Secondary outcomes are generally less conclusive when they are not the designated primary endpoint and when many outcomes or time points may be examined. Repeated testing increases the chance of apparently notable findings by chance unless the analysis plan accounts for multiplicity. The registry's multiplicity strategy is not reported in the registry record. Accordingly, the secondary findings add context, but should carry less inferential weight than the prespecified primary analysis and should not be treated as standalone proof of an effect.

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

• Change From Baseline in CFQ-R RSS Score at Day 14
• Change From Baseline in CFQ-R RSS Score at Day 42
• Change From Baseline in CFQ-R Physical Functioning Domain Score
• Number of Participants Using Additional (Nonprotocol-specified) Antipseudomonal Antibiotics During Study
• Number of Participants Hospitalized During Study
• Change From Baseline in Log10 Pseudomonas Aeruginosa (PA) Colony Forming Units (CFUs) in Sputum at Day 28
• Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted

9. Statistical Interpretation

10. Statistical Methods Explained

What does a change score represent?

A change score expresses the difference between a measurement at baseline and a later measurement. For this endpoint, the measurement is the CFQ-R RSS score, and the primary follow-up is Day 28. Because higher scores indicate fewer symptoms, a positive change represents movement in the scale's favorable direction. A group mean summarizes the average change; it does not describe every participant's response or the distribution of individual experiences.

What is a least-squares mean?

A least-squares mean is an adjusted group estimate from a statistical model. The registry says baseline RSS and age group were included as covariates. Adjustment accounts for those specified variables in estimating the comparison, rather than simply comparing the unadjusted group averages. The exact model specification beyond the reported ANCOVA and covariates is not reported in the registry record. Least-squares means are model-based estimates and should be understood alongside their uncertainty, rather than as raw observations.

What does ANCOVA contribute?

Analysis of covariance (ANCOVA) compares groups while accounting for selected covariates. In this trial, the sponsor's reported analysis is an ANCOVA of final values, with the registry identifying baseline CFQ-R RSS and age group as covariates in the endpoint analysis. Covariate adjustment can improve precision when the variables are relevant to the outcome, but it does not remove uncertainty or correct for unreported sources of bias. The registry record does not provide the full statistical analysis plan or enough detail to reconstruct every model choice.

How should the recalculation be understood?

The recalculated mean difference uses the posted group means and standard errors to form a simple unadjusted comparison. It is not the sponsor's covariate-adjusted analysis. The posted standard errors describe uncertainty around each arm's estimated mean, while the approximate pooled standard deviation used for standardized effect-size calculations is itself derived from summary information. Such recalculation is useful as a transparent check on scale and direction, but it cannot reproduce the full participant-level ANCOVA. The registry's reported analysis remains the sponsor's analysis.

What does a p-value say?

A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under the model assumptions, if the null hypothesis were true. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result will replicate. The primary unadjusted recalculation has p = 0.445; the sponsor's reported analysis has p = 0.433. Neither number conveys the size of uncertainty by itself. The confidence interval gives a more direct range of values compatible with the estimate and model.

Why do missing data and analysis population matter?

The registry describes an intent-to-treat population as participants who received at least part of one dose of AZLI or placebo. It states that missing baseline data were not imputed. Missing post-baseline data for participants who withdrew due to an adverse event or study-drug intolerance were imputed with a worst-case value. The description of imputation for other missing post-baseline values is incomplete in the registry record, so the method for those data is not reported in the registry record. Imputation makes assumptions about unobserved outcomes; different assumptions can affect estimated group changes and uncertainty.

Analysis-population definitions determine which participants contribute to an estimate, while missing-data rules determine how unavailable measurements are handled. The reported primary outcome counts are not necessarily the number originally randomized to each group. The registry record does not provide enough information to assess every consequence of missingness or to compare alternative missing-data assumptions.

Why consider multiple outcomes?

The registry lists primary and secondary outcomes, including repeated assessments of CFQ-R RSS and other clinical measures. When many outcomes or time points are tested, the chance of at least one apparently notable result due to random variation can rise. Statistical approaches such as multiplicity adjustment can address some of that issue, but the registry's multiplicity plan is not reported in the registry record. Secondary p-values should therefore be treated as exploratory unless an appropriate prespecified testing strategy is documented.

11. Confidence Intervals and Precision

The primary recalculated mean difference is 1.81 units, with a 95% confidence interval from -2.834 to 6.454. The interval crosses zero and includes values on both sides of it. In general, a confidence interval describes the range of estimates compatible with the observed data and the statistical model at the stated confidence level. It is not a guarantee that the true value lies within the interval, nor does it assign probabilities to individual values inside it.

The width of the interval indicates appreciable uncertainty around the primary recalculated estimate. Its lower end permits a difference favoring placebo, while its upper end permits a larger positive difference for AZLI. The estimate's positive direction should therefore not be read alone as a settled finding. The sponsor's ANCOVA interval, -2.83 to 6.44, has the same broad interpretation and also includes zero.

These intervals reflect different analyses: the recalculated interval comes from an approximate unadjusted comparison, whereas the sponsor's reported interval is from ANCOVA. They are close, but they are not interchangeable. The registry record does not report a threshold for a clinically important CFQ-R RSS difference, so the interval cannot be classified against such a threshold using the record alone.

Precision is also distinct from statistical significance. A wide interval may leave substantial uncertainty even when its point estimate is of interest; a narrow interval can still encompass effects that are not important to patients. Here, the interval supports a cautious account of the estimate rather than a firm conclusion about the size or clinical meaning of the group difference.

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 both arms and not total events. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is a stated fraction of the observed effect. These are planning assumptions for an illustration; the original trial's sample-size justification and design assumptions are not reported in the registry record.

For the primary outcome, planning around 100% of the observed effect gives 1,055 participants per arm for 80% power and 1,412 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,874 participants per arm for 80% power and 2,509 participants per arm for 90% power. Planning for 50% of the observed effect gives 4,217 participants per arm for 80% power and 5,645 participants per arm for 90% power.

Power is the chance, under the planning assumptions and for the stated effect, of detecting a difference using the specified statistical test. The 80% and 90% columns represent different target chances of detection; the higher target generally calls for more participants. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm. The curve is another way of displaying how the assumed effect and required sample size relate.

These figures are planning illustrations based on the observed effect, not observed power for the completed trial. Observed power is not a useful substitute for reading the estimate and its confidence interval.

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 = 1.810; pooled standard deviation σ = 14.832.
2. n = 2 × (1.96 + 0.842)² × 14.832² / 1.810² = 1,054.0, rounded up to 1,055 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 <- 1.81                      # observed difference in means
sigma <- 14.8315222284465                     # 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(712166)
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 = 1,055 (80% power), 1,412 (90% power)
 75% of observed effect: n per arm = 1,874 (80% power), 2,509 (90% power)
 50% of observed effect: n per arm = 4,217 (80% power), 5,645 (90% power)
power.t.test: 1055 
Simulated power at n = 1,055 per arm: 0.795 (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 reported primary analysis is an ANCOVA of final values. It estimates a mean difference of 1.80, with a 95% confidence interval from -2.83 to 6.44 and p = 0.433. The simple recalculation from posted summary statistics estimates a mean difference of 1.81, with a 95% confidence interval from -2.834 to 6.454 and an unadjusted p-value of 0.445.

The estimates are close, and both intervals include zero. The small numerical differences are consistent with the analyses using different approaches: the sponsor's result is covariate-adjusted, whereas the recalculation is unadjusted and approximate. The recalculation is a secondary statistical check, not a replacement for the reported analysis. The sponsor's own analysis takes precedence as the trial's reported result.

Neither analysis establishes the precision needed to make a firm claim about the size of the between-group difference. The sponsor's estimate and the recalculation should be read with their confidence intervals, and the available registry record does not supply the full analysis plan needed to reproduce the ANCOVA from participant-level data.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and multiple secondary outcomes, including repeated CFQ-R RSS measurements and other clinical measures. Testing many outcomes can increase the overall chance of a false-positive finding when each test is considered separately. A prespecified hierarchy or multiplicity adjustment can help control that risk. The registry's approach to multiplicity, including whether any adjustment or testing hierarchy was planned, is not reported in the registry record.

The primary endpoint is therefore the clearest statistical anchor among the outcomes. Secondary estimates may help describe the pattern across measures, but unadjusted secondary p-values should be interpreted cautiously when the family of tests and intended inferential strategy are unclear. A nominal result on a secondary measure would not automatically constitute confirmatory evidence.

The primary population is described as intent-to-treat, defined as participants who received at least part of one dose of AZLI or placebo. The registry states that missing baseline data were not imputed. For post-baseline data, participants who withdrew due to an adverse event or study-drug intolerance had a worst-case value imputed. It begins to describe imputation for other missing post-baseline data, but the details are incomplete; the approach for those other missing values is not reported in the registry record.

Missing-data assumptions can affect both the estimated group difference and its uncertainty, especially when outcomes are unavailable for reasons related to health or treatment experience. The registry does not provide enough detail to assess the robustness of the result under alternative assumptions. The primary outcome counts are reported by arm, but the full flow from randomization through analysis and the reasons for all missing measurements are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cough (3.9%), pyrexia (2.5%), breath sounds abnormal (1.3%), dyspnoea (1.3%), gastrooesophageal reflux disease (1.3%).

For serious adverse events, the registry reports 3 participants affected among 81 at risk in the placebo group and 9 among 76 at risk in the AZLI group. These figures describe participants recorded as having a serious adverse event during the study. They do not, by themselves, establish that treatment caused an event or explain its severity, timing, or relationship to study drug.

The registry also reports other adverse events for 62 of 81 participants in the placebo group and 58 of 76 participants in the AZLI group. The listed serious-event terms include cough at 3.9% and pyrexia at 2.5%; breath sounds abnormal, dyspnoea, gastrooesophageal reflux disease, and malnutrition are each listed at 1.3%. The record does not provide enough information in these figures to compare event types on a causal basis. Deaths are not reported in the registry record.

Safety counts should be interpreted alongside the trial's population, duration, event definitions, and completeness of follow-up. They are descriptive counts, not a stand-alone measure of comparative risk.

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

The primary result describes an estimated difference in change in patient-reported respiratory symptoms between AZLI and placebo over Day 0 to Day 28. The point estimate is positive for AZLI under the scale's direction, but the confidence interval is broad and includes zero. The posted data therefore leave uncertainty about the magnitude and direction of the true group difference.

This result does not establish that AZLI does or does not work. It is not proof of no difference, because the interval includes positive values; it is not proof of a meaningful benefit, because the interval also includes zero and negative values. The registry does not report a threshold for a clinically important change, so the clinical importance of possible differences cannot be judged against a trial-specific threshold from this record.

The endpoint is a patient-reported symptom scale and captures an aspect of health-related quality of life. It complements other measures, but does not represent every dimension of cystic fibrosis or lung disease. The additional listed outcomes include symptoms at other times, physical functioning, antibiotic use, hospitalization, sputum bacterial counts, and FEV1; numerical results for some listed outcomes are not reported in the registry record.

Interpretation also depends on the analysis population, covariate adjustment, and handling of missing outcomes. The registry describes some of these choices but does not report complete details for all missing-data procedures or the multiplicity plan. Those gaps limit how fully the analysis can be independently assessed. The result is best understood as an uncertain estimate from this completed randomized trial, rather than a definitive statement about individual response or clinical effect.

18. Why This Trial Matters Statistically

This trial illustrates why an estimated effect should be read together with its uncertainty. The primary estimate points toward a larger mean change in CFQ-R RSS for AZLI, yet the confidence interval spans values on both sides of zero. A point estimate alone can give an incomplete impression; the interval makes clear that the posted result allows a range of plausible effects.

It also demonstrates the distinction between a sponsor-reported adjusted analysis and a simple recalculation from summary statistics. The close estimates provide a useful consistency check, but the methods differ and the recalculation cannot reproduce participant-level modeling. Keeping the sponsor's ANCOVA as the reported analysis avoids treating an approximate unadjusted calculation as equivalent evidence.

The trial has multiple symptom assessments and other outcomes, making multiplicity and selective interpretation relevant statistical concerns. The registry identifies a primary endpoint, but its multiplicity strategy and complete missing-data methods are not reported in the registry record. These omissions affect how confidently secondary findings can be interpreted and reproduced.

Finally, the planning illustrations show how sample-size requirements depend on the effect a future study aims to detect and the desired power. Their figures are not a retrospective measure of whether the completed trial had adequate power. This distinction helps prevent planning calculations from being misread as evidence about the trial's observed result.

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 primary outcome is a patient-reported scale, and the registry record does not report a threshold for a clinically important difference. Thus, statistical estimates cannot be translated into a judgment of clinical importance using the registry information alone. The primary confidence interval is broad and includes zero, leaving substantial uncertainty around the estimated difference.

The registry's description of missing-data handling is incomplete. It states that missing baseline data were not imputed and describes worst-case imputation for some missing post-baseline data, but the approach for other missing post-baseline values is not reported in the registry record. The full participant flow, reasons for missing measurements, and sensitivity analyses are also not reported in the registry record.

The registry reports quadruple masking but does not specify which study roles were masked. It does not report the randomization or allocation-concealment details, the original sample-size justification, or the full statistical analysis plan. The multiplicity approach is not reported in the registry record, which limits interpretation of secondary testing. Numerical results are also not reported in the registry record for several listed secondary outcomes.

These limitations do not negate the randomized comparison, but they constrain how completely its precision, potential bias, and secondary findings can be assessed from the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa — NCT00712166.
• Registry record last updated 2010-12-20; status last verified 2010-11.
• Results first posted 2010-12-20.
• 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.

23. Record Summary

NCT00712166 is a completed Phase 3 randomized, placebo-controlled, parallel-group trial of AZLI 75 mg three times daily versus placebo in people with cystic fibrosis, mild lung disease, and Pseudomonas aeruginosa infection. Enrollment is recorded as 160. The primary endpoint was change from baseline in CFQ-R RSS at Day 28.

The sponsor-reported ANCOVA estimated a mean difference of 1.80, with a 95% confidence interval from -2.83 to 6.44 and p = 0.433. The unadjusted recalculation estimated a difference of 1.81, with a 95% confidence interval from -2.834 to 6.454. Both intervals include zero and indicate uncertainty about the size and direction of the group difference.

The record lists several secondary outcomes and reports numerical results for three secondary continuous measures. The multiplicity plan and some missing-data procedures are not reported in the registry record. Serious adverse events were recorded in both groups; the counts are descriptive and do not establish causation.