Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients (NCT01746095), a randomized phase 2 study. The primary outcome is Change From Baseline in MRSA Sputum Density..

2. Clinical Question

The trial record describes the study purpose as assessing whether AeroVanc is safe and effective in reducing the number of MRSA colony-forming units in the lungs. The posted primary endpoint is the change from baseline in MRSA sputum density at Day 29. It is a continuous laboratory measure, rather than a count of respiratory symptoms or an assessment of lung function. The clinical question is thus specific: whether the assigned inhaled powder groups differed on this sputum measure at the stated timepoint.

The record lists 87 enrolled participants. The posted primary outcome results use a modified ITT population, and the analyzed group sizes differ across arms. Those groups and their results describe the participants with endpoint data under the stated population definition; they should not be confused with total enrollment. The record does not report the original assumptions used to select the planned enrollment or a formal sample-size justification.

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled study with a parallel-group design. The registry record lists quadruple masking. It enrolled 87 participants and is marked completed. The record gives a start date of 2013-03 and a primary completion date of 2014-11.

Participants were assigned to inhaled vancomycin hydrochloride powder or matching placebo powder. AeroVanc had two dose groups: 32 mg twice daily and 64 mg twice daily. Each dose had its corresponding placebo group, described as placebo to 32 mg or placebo to 64 mg. This arrangement matters when reading the posted contrasts: the 32 mg dose is compared with placebo to 32 mg, and the 64 mg dose with placebo to 64 mg. The record does not describe a direct comparison between the two active doses.

The primary analysis population is described as modified ITT. It included randomized patients who received any amount of study drug and had at least one scheduled post-baseline measurement. The arm-specific primary endpoint group sizes were 17 for AeroVanc 32 mg, 17 for placebo to 32 mg, 15 for AeroVanc 64 mg, and 22 for placebo to 64 mg. These are the counts attached to the posted primary outcome, not an alternative statement of total enrollment.

The record lists change from baseline in MRSA sputum density at Day 29 as the primary endpoint. Other listed outcomes include an earlier sputum-density measurement, lung-function measures, respiratory symptom scores, time to other antimicrobial medication, time to exacerbation, and high-sensitivity CRP. The original allocation ratio, details of sequence generation, and further operational information about masking 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: Modified ITT population, which included all randomized patients who received any amount of study drug and had at least one scheduled post baseline measurement.

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 MRSA Sputum Density., measured over Day 29 of treatment period.

The primary endpoint is change from baseline in MRSA sputum density at Day 29 of the treatment period. Sputum density is measured in Log10 CFU/mL, referring to the concentration of MRSA colony-forming units in a sputum culture. Day 1 is defined as the start of AeroVanc or placebo administration. The reported arm summaries are least-squares means, with standard errors as the measure of dispersion.

A sputum culture provides a direct microbiological measure related to the study’s stated aim of reducing MRSA in the lungs. Expressing the measure on a log scale can make a wide range of bacterial concentrations easier to analyze and describe. General statistical context: a change-from-baseline endpoint uses each participant’s starting measurement as a reference, then summarizes how the measure changed by the specified follow-up time. This differs from simply comparing the follow-up values without accounting for baseline.

The endpoint is a surrogate laboratory measure, not a direct summary of symptoms, lung function, or later clinical events. Its interpretation depends on the measurement process, the participants with available data, and the statistical analysis used. The registry record identifies the modified ITT population and the Day 29 timepoint, but does not report further detail about the endpoint’s analysis model or handling of missing measurements. The posted values therefore describe the reported sputum-density changes and their uncertainty; they do not by themselves establish how those changes relate to other outcomes.

7. Results Posted in the Registry

• AeroVanc 32 mg: mean -0.25 versus -0.30 on control; difference 0.05 (95% CI -0.45 to 0.55), standardized effect d = 0.07; z-test p = 0.846.
• AeroVanc 64 mg: mean -0.63 versus -0.30 on control; difference -0.33 (95% CI -0.91 to 0.25), standardized effect d = -0.40; z-test p = 0.263.
• Placebo to 64 mg: mean 0.16 versus -0.30 on control; difference 0.46 (95% CI -0.07 to 0.99), standardized effect d = 0.53; z-test p = 0.090.

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 MRSA Sputum Density.

• 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:
  • AeroVanc 32 mg: mean -0.27 versus -0.28 on control; difference 0.01 (95% CI -0.59 to 0.61), standardized effect d = 0.01; z-test p = 0.974.
  • AeroVanc 64 mg: mean -1.04 versus -0.28 on control; difference -0.76 (95% CI -1.34 to -0.18), standardized effect d = -0.81; z-test p = 0.010.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AeroVanc 32 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for AeroVanc 64 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in FEV1

• 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:
  • AeroVanc 32 mg: mean 0.53 versus 1.15 on control; difference -0.62 (95% CI -4.36 to 3.12), standardized effect d = -0.11; z-test p = 0.745.
  • AeroVanc 64 mg: mean -0.68 versus 1.15 on control; difference -1.83 (95% CI -5.31 to 1.65), standardized effect d = -0.36; z-test p = 0.302.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AeroVanc 32 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AeroVanc 64 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in FVC

• 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:
  • AeroVanc 32 mg: mean -0.07 versus 1.67 on control; difference -1.74 (95% CI -5.28 to 1.80), standardized effect d = -0.33; z-test p = 0.336.
  • AeroVanc 64 mg: mean -0.47 versus 1.67 on control; difference -2.14 (95% CI -6.15 to 1.87), standardized effect d = -0.37; z-test p = 0.296.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AeroVanc 32 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AeroVanc 64 mg and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results cover an earlier sputum-density measurement and changes in FEV1 and FVC at Day 29. Taken together, they do not form a uniform pattern across all outcomes and dose comparisons. The earlier sputum measure includes a more pronounced decrease in the AeroVanc 64 mg arm than in its placebo group, while the Day 29 lung-function comparisons have uncertainty spanning zero. The 32 mg comparisons do not show a clear separation from their corresponding placebo groups in the posted estimates.

These secondary findings add context to the primary Day 29 sputum-density result but do not replace it. The earlier measurement concerns a different timepoint, and FEV1 and FVC measure lung function rather than MRSA sputum density. Agreement or disagreement across distinct outcomes is not automatic evidence that one measure confirms another. The available endpoint summaries should be considered individually and in light of their uncertainty, analysis populations, and timing.

The registry record lists additional outcomes, including respiratory symptom diary scores, time to use of other antimicrobial medication, time to exacerbation under Fuchs criteria, and high-sensitivity CRP. Numerical results for these listed measures are not reported in the registry record. The record also lists a repeated sputum-density outcome title, so the list of outcome names does not by itself clarify every distinct measure or analysis.

Unadjusted secondary comparisons carry less weight when several endpoints, doses, and timepoints may be examined. General statistical context: repeated testing can make chance findings more likely unless a prespecified hierarchy, correction, or other multiplicity strategy is used. No such strategy is reported in the registry record. The secondary results are therefore best read as supportive or exploratory descriptions, not as a separate set of definitive tests. They also do not resolve the uncertainty in the primary contrast or establish effects on outcomes whose numerical results are absent.

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

• Change From Baseline in MRSA Sputum Density.
• Change From Baseline in MRSA Sputum Density.
• Change From Baseline in FEV1
• Change From Baseline in FVC
• Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary (CFRSD-CRISS) Scores
• Time From Start of Dosing to First Administration of Other Antimicrobial Medications (Oral, Intravenous and/or Inhaled) Due to Respiratory Symptoms.
• Time From Start of Dosing to Exacerbation of Signs/Symptoms (Fuchs Criteria).
• Change From Baseline in High Sensitivity CRP

9. Statistical Interpretation

10. Statistical Methods Explained

For the primary endpoint, the registry record reports least-squares mean changes from baseline and standard errors for each arm. A least-squares mean is a model-based mean, commonly adjusted for features included in the model. The registry record does not describe the model or its covariates, so the adjustment details cannot be inferred. A standard error describes the statistical uncertainty in an estimated mean; it is not the same quantity as the spread of individual participants’ measurements.

What does a treatment contrast represent?

A contrast expresses the difference between two group estimates. The recalculated primary contrasts compare AeroVanc 32 mg with placebo to 32 mg, and AeroVanc 64 mg with placebo to 64 mg. The signs depend on the order of subtraction: the posted calculations subtract the corresponding placebo mean from the AeroVanc mean. A positive or negative contrast describes direction on the measurement scale, but direction alone does not show how certain the estimate is or whether the difference is important to patients.

The contrast estimates are simple unadjusted recalculations from the posted arm summaries. Because only standard errors, rather than standard deviations, are posted, the pooled standard deviations used for these calculations are approximate. The registry record does not report sponsor-level contrast estimates or p-values for these outcomes. The recalculations are therefore useful as a transparent comparison of the posted summaries, but they should not be mistaken for the sponsor’s prespecified analysis. The record does not report a discrepancy between these calculations and a sponsor analysis.

How should a p-value be read?

A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The p-values attached to the recalculated primary contrasts are unadjusted. General statistical context: when several outcomes, doses, or timepoints are examined, the chance of at least one small p-value can increase if no adjustment or other multiplicity strategy is used. The registry record does not report a multiplicity plan, so the unadjusted values should be treated as exploratory evidence rather than as a complete account of confirmatory testing.

What does the analysis population tell us?

The stated modified ITT population includes randomized patients who received any amount of study drug and had at least one scheduled post-baseline measurement. This definition means the primary analysis is not simply a count of everyone enrolled or everyone randomized. The posted group sizes are 17, 17, 15, and 22 across the four primary endpoint arms. General statistical context: restricting an analysis based on post-randomization treatment receipt or measurement availability can affect how closely a comparison retains the protection of randomization, particularly if exclusions relate to prognosis or response. The registry record does not provide enough information to assess the reasons individual participants were omitted from the endpoint analysis.

Missing-data methods, assumptions about unobserved outcomes, sensitivity analyses, and the handling of protocol deviations are not reported in the registry record. Those details matter because results can depend on how unavailable measurements are treated. The posted summaries therefore cannot establish whether missing observations were balanced between groups or whether alternative assumptions would change the estimated contrasts.

Why can over-dispersion matter?

General statistical context: over-dispersion occurs when observed variability is greater than a statistical model expects. For continuous outcomes, greater variability makes estimates less precise and usually widens confidence intervals; for count outcomes, it can make a simple count model understate uncertainty. The record does not report an over-dispersion assessment, and the primary endpoint is posted as a continuous measure. It would be inappropriate to assume that such an assessment was performed or that it affected the analysis.

Overall, the available information supports a descriptive reading of the arm means and an approximate, unadjusted reconstruction of contrasts. It does not give the full protocol analysis plan, model specification, or missing-data strategy. Those omissions are reasons to qualify the interpretation, not grounds to infer that a particular method was used.

11. Confidence Intervals and Precision

A confidence interval gives a range of values compatible with the data under the assumptions used to calculate it. General statistical context: a narrower interval indicates greater precision, while a wider interval indicates that the estimate is less tightly located. An interval that includes zero is compatible with no average difference as well as with differences in either direction, at the confidence level used. The confidence level for the posted recalculations is not stated separately in the registry record.

For the Day 29 primary contrasts, the recalculated confidence intervals for both AeroVanc doses include zero. The 32 mg comparison is centered close to zero, and its interval extends in both directions around the estimate. The 64 mg comparison is centered on a negative estimate, but its interval also extends across zero. Thus, the point estimates alone should not be treated as precise descriptions of the underlying group difference. The corresponding unadjusted p-values are 0.846 and 0.263.

The uncertainty is relevant alongside the endpoint group sizes: the primary comparisons include 17 participants per arm for the 32 mg pair and 15 and 17 for the 64 mg pair. Small groups can yield limited precision, though precision also depends on how variable the measurements are. The registry record reports standard errors for the arm means, not standard deviations, and the recalculated intervals use approximate standard deviations derived from those standard errors.

These intervals quantify statistical uncertainty under the calculation assumptions; they do not account for unreported sources of uncertainty such as missing-data assumptions, model choices, or multiple testing. Nor do they indicate whether a difference would be clinically meaningful. The registry record does not report a threshold for a meaningful change in sputum density. The estimates should therefore be read as uncertain comparisons on the posted measurement scale, rather than as exact treatment effects.

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 figures are illustrations based on the observed effect, not the original trial design. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect. The figures are participants per arm, not total participants and not total events; the total-event convention applies only to time-to-event outcomes.

The 80% power column gives the approximate number of participants per arm for a design with an 80% chance of detecting the assumed effect under the stated assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. These are design probabilities under hypothetical conditions, not probabilities that a result from the completed trial is true.

For example, planning around 100% of the observed AeroVanc 64 mg contrast gives 98 participants per arm for 80% power and 131 per arm for 90% power. Planning around 75% of that observed effect gives 174 and 233 participants per arm, respectively; planning around 50% gives 391 and 523. The figures for the AeroVanc 32 mg contrast are much larger: at 100% of its observed effect, the estimates are 3,517 participants per arm for 80% power and 4,708 for 90% power. This reflects how a smaller observed contrast relative to variability translates into a larger planning requirement.

Across the scenarios, smaller effects require more participants to detect with the same target power, and a higher target power also requires more participants. These illustrations are not observed power for the completed trial. The registry record does not report the original design assumptions, target effect, or sample-size justification, so these planning calculations cannot be used to reconstruct why 87 participants were enrolled.

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 = 0.050; pooled standard deviation σ = 0.748.
2. n = 2 × (1.96 + 0.842)² × 0.748² / 0.050² = 3,516.4, rounded up to 3,517 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 <- 0.05                      # observed difference in means
sigma <- 0.748346510648643                     # 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(1746095)
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 = 3,517 (80% power), 4,708 (90% power)
 75% of observed effect: n per arm = 6,252 (80% power), 8,369 (90% power)
 50% of observed effect: n per arm = 14,066 (80% power), 18,831 (90% power)
power.t.test: 3517.4 
Simulated power at n = 3,517 per arm: 0.799 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint, several secondary outcomes, and comparisons involving two AeroVanc doses and corresponding placebo groups. This creates multiple opportunities for statistical testing across measures and timepoints. The record does not report whether a hierarchy of hypotheses, adjustment for multiple comparisons, or another multiplicity strategy was specified. The recalculated p-values are unadjusted, and no correction should be assumed.

Multiplicity matters because each statistical test has a chance of producing an apparently unusual result even when there is no true difference. When many tests are considered together, that chance can increase. General statistical context: a prespecified strategy can distinguish a primary confirmatory test from secondary or exploratory tests and can control how evidence is interpreted across the family of comparisons. Without the strategy and full analysis plan, the secondary p-values and dose-specific findings should be interpreted cautiously. The registry record reports no formal secondary analyses in the posted analysis listing.

The modified ITT population is defined as randomized patients who received any amount of study drug and had at least one scheduled post-baseline measurement. This is the population attached to the primary result. It differs conceptually from an analysis including every randomized participant regardless of post-randomization treatment receipt or availability of measurements. The registry record does not report additional analysis-population results that would show whether conclusions were consistent across different populations.

Methods for missing data are not reported in the registry record. In particular, the record does not specify how missing Day 29 measurements were handled, what assumptions were made about their values, or whether sensitivity analyses assessed alternative assumptions. The reasons for missing measurements and their distribution across groups are also not reported. These omissions limit assessment of potential bias because the analyzed endpoint group may not include every randomized participant.

The record identifies the endpoint as a least-squares mean and reports standard errors, but the model specification, covariate adjustment, and detailed testing procedure are not reported. The record also does not report interim analyses, stopping rules, or the original sample-size justification. These features should be treated as unreported rather than inferred from the completed status or the posted estimates.

15. 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: infective pulmonary exacerbation of cystic fibrosis (15.0%), hyperglycemia (5.0%), pain (5.0%), infective exacerbation of bronchiectasis (5.0%), pneumonia (4.3%).

Safety results are reported by four groups: AeroVanc 32 mg, placebo to 32 mg, AeroVanc 64 mg, and placebo to 64 mg. The registry record lists serious adverse events affecting 4 of 20 participants in AeroVanc 32 mg, 2 of 20 in placebo to 32 mg, 1 of 24 in AeroVanc 64 mg, and 4 of 23 in placebo to 64 mg. The corresponding counts at risk are stated with each group. These counts should be read by group, rather than combined across the two placebo groups or the two active doses.

Other adverse events affected 18 of 20 participants in each 32 mg group, 20 of 24 in AeroVanc 64 mg, and 19 of 23 in placebo to 64 mg. No deaths are listed in any group. The registry record lists serious adverse event terms including infective pulmonary exacerbation of cystic fibrosis at 15.0%, hyperglycemia at 5.0%, pain at 5.0%, infective exacerbation of bronchiectasis at 5.0%, pneumonia at 4.3%, and pleural effusion at 4.3%. It does not provide a detailed account of the timing, duration, or attribution of each event in these summary details.

These event counts describe what was recorded during the study; they do not by themselves establish that an event was caused by treatment or that group risks differ. Group sizes are limited, and the registry record does not report a formal statistical comparison of safety outcomes. Safety findings should be interpreted as descriptive trial data, not as advice about treatment.

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

The posted primary endpoint results describe changes in MRSA sputum density over the treatment period and show two dose-specific comparisons with corresponding placebo groups. The 32 mg arm means were close to the corresponding placebo mean, while the AeroVanc 64 mg mean was lower than its placebo group mean at Day 29. However, the recalculated contrasts for both doses have confidence intervals that include zero, and their unadjusted p-values are 0.846 and 0.263. The data therefore leave uncertainty about the size and direction of the underlying average differences.

This statistical reading is limited to the defined endpoint, timepoint, and modified ITT population. It does not establish whether the sputum-density changes translate into differences in respiratory symptoms, lung function, exacerbations, or use of other antimicrobial medication. Some of those outcomes are listed in the registry record, but numerical results for several are not reported there. The posted secondary results are also subject to the uncertainty and multiplicity concerns.

The trial enrolled 87 participants, while the primary endpoint arm sizes range from 15 to 22. These group sizes and the approximate nature of the recalculated standard deviations help explain why the contrasts are not highly precise. A confidence interval that includes zero does not prove there is no difference; it indicates that the data and calculation assumptions do not tightly distinguish the estimate from zero. Likewise, an estimated contrast should not be presented as a certain or clinically meaningful effect without an appropriate clinical threshold, which is not reported in the registry record.

The registry record does not report the original sample-size rationale, full analysis plan, handling of missing data, or multiplicity strategy. Consequently, the posted data can inform a cautious description of the measured outcomes, but they cannot resolve how robust the findings are to analysis choices that are not documented. No treatment recommendation follows from these statistics alone.

17. Why This Trial Matters Statistically

This trial raises several statistical issues common to clinical research. First, the primary outcome is continuous and reported as a least-squares mean change with a standard error. Understanding the distinction between the estimated average, the uncertainty around it, and variation among individual participants is essential: the standard error is not a direct description of individual-level spread.

Second, there are two active doses and two dose-specific placebo groups. Preserving those pairings is important because the posted design does not describe a single shared placebo comparison. A comparison between active doses, or a pooled placebo analysis, would answer a different question from the dose-specific contrasts. The arm summaries also illustrate why comparing each group’s change in isolation is not the same as estimating a randomized between-group difference.

Third, the confidence intervals are central to interpretation. The observed estimates are not precise enough to exclude zero under the recalculated comparisons. Point estimates can appear different across arms, but their uncertainty needs to be considered before drawing conclusions. The sample-size illustrations further show how the number of participants needed for a future study depends strongly on the effect size assumed relative to variability; those planning figures do not explain the original enrollment.

Finally, the available record leaves important analysis details unreported, including multiplicity handling and missing-data methods. These are not minor technicalities: they affect how confirmatory the evidence is and how broadly the results can be interpreted. A careful reading separates the posted descriptive findings from unknown aspects of the original analysis plan, and keeps microbiological, lung-function, symptom, and safety outcomes distinct.

18. 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 endpoint results are reported for a modified ITT population rather than all enrolled participants. The definition requires receipt of some study drug and at least one scheduled post-baseline measurement. The registry record does not report how many participants were randomized but excluded from this endpoint population, why measurements were unavailable, or whether exclusions differed across groups.

Only summary statistics are available for the comparisons. The registry record does not report sponsor-level estimates and inferential results for the primary contrasts, a full statistical model, or details of covariate adjustment. The recalculated contrasts are unadjusted and use approximate standard deviations derived from the arm standard errors. They should not be treated as a substitute for an undocumented sponsor analysis.

The record does not describe missing-data procedures, sensitivity analyses, a multiplicity strategy, or the original sample-size assumptions. It also does not report the confidence level separately for the recalculated intervals. These gaps prevent a full assessment of how robust the results are to analysis choices, or how the original trial was planned. Several listed secondary outcomes have no numerical results in the registry record, limiting assessment of consistency across the full outcome set.

Interpretation is further constrained by the modest endpoint group sizes, the short stated endpoint timeframe, and reliance on a sputum-density measure for the primary question. The record does not state a threshold for a clinically meaningful change or provide enough information to relate the laboratory measure to patient experience. The two placebo groups are dose-specific and should not be assumed interchangeable. These limitations qualify the evidence but do not establish that any particular unreported method or analysis would change the findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of AeroVanc for the Treatment of Persistent MRSA Lung Infection in Cystic Fibrosis Patients — NCT01746095.
• Registry record last updated 2020-01-13; status last verified 2019-12.
• Results first posted 2020-01-13.
• 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.

22. Record Summary

The registry record describes a completed, randomized, double-blind, placebo-controlled Phase 2 parallel-group study of inhaled AeroVanc in people with cystic fibrosis and persistent MRSA lung infection. Quadruple masking is listed. The record gives enrollment as 87, with a start date of 2013-03 and primary completion in 2014-11.

The primary endpoint is change from baseline in MRSA sputum density at Day 29, measured in Log10 CFU/mL. The modified ITT population includes randomized patients who received any study drug and had at least one scheduled post-baseline measurement. Posted arm means show a decrease in both 32 mg groups and in AeroVanc 64 mg, with an increase in placebo to 64 mg. Recalculated unadjusted dose-specific contrasts have confidence intervals that include zero.

The registry record also lists secondary outcomes and adverse events, but does not report the original sample-size justification, detailed statistical plan, multiplicity strategy, or missing-data methods. Secondary numerical results are not available for every listed outcome. The posted results support cautious description of the measured data, with uncertainty retained in the interpretation.