Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia (NCT01969799), a randomized phase 2 study. The primary outcome is Change From Baseline in Clinical Pulmonary Infection Score (CPIS) For Each Patient, Value Obtained From a Daily Assessment Over the 10 Day Study Period Was Compared to Baseline, and the LSM Data Represent the Change From Baseline Data Over All Days ..

2. Clinical Question

The trial concerns an adjunctive inhaled treatment rather than a comparison of inhaled treatment with no pneumonia treatment. The registry describes the intended assessment as safety and efficacy in mechanically ventilated patients with Gram-negative pneumonia receiving intravenous antibiotics. The primary endpoint follows daily CPIS assessments and summarizes change from baseline over the treatment period. CPIS ranges from 0 to 13, with 13 described as the worst score and zero as a healthy patient with no evidence of pneumonia.

The reported primary comparison is between the Amikacin Fosfomycin Inhalation Solution group and the Aerosolized Placebo group. Its interpretation is therefore about the difference in the recorded CPIS change between these trial groups, not about a comparison with other treatment approaches or populations. The registry record does not report further eligibility details, such as specific clinical thresholds for enrollment.

3. Trial Design

This was a phase 2, randomized, parallel-group study with quadruple masking and a placebo comparator. The registry lists enrollment of 143 and status as completed. The intervention was aerosolized amikacin and fosfomycin delivered through the investigational eFlow Inline System; the comparator was aerosolized placebo using that system. The treatment schedules were twice daily for 10 days. The registry lists Cardeas Pharma as the sponsor.

The primary outcome was assessed in the MITT population. The registry does not expand that population label in the reported results. The primary assessment was based on daily CPIS measurements over the 10 day treatment period, with a blinded central reviewer described as the assessor to minimize inter-observer variability. The reported primary arm summaries each have 71 participants. The safety counts use denominators of 71 for the inhaled combination group and 72 for the placebo group; the record does not explain the difference between these denominators and the primary endpoint denominators.

The registry lists secondary outcomes covering mortality and clinical cure, mortality and ventilator-free days, days free of mechanical ventilation, ICU days, microbiological response among participants positive for multi-drug resistant Gram-negative bacteria, mortality through Day 28, and clinical relapse. Numerical results are posted for days free of mechanical ventilation, ICU days, and the microbiological response outcome. Numerical results for the other listed secondary outcomes are not reported in the registry record.

The registry record does not report the original sample-size justification, detailed randomization procedures, the trial's prespecified statistical plan, interim analyses, or a fuller account of the analysis populations. Those details should not be inferred from the reported design labels or from sample-size planning illustrations based on observed results.

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: The trial was designed to have 150 patients, hoping to have at least 140 patients with proven gram negative pneumonia. The trial was terminated at 143 when that goal was achieved.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: MITT

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 Clinical Pulmonary Infection Score (CPIS) For Each Patient, Value Obtained From a Daily Assessment Over the 10 Day Study Period Was Compared to Baseline, and the LSM Data Represent the Change From Baseline Data Over All Days ., measured over 10 day treatment period..

The primary endpoint is change from baseline in Clinical Pulmonary Infection Score (CPIS), evaluated through daily assessments over the 10 day treatment period. The registry reports least-squares mean changes across all days and identifies the primary population as MITT. CPIS ranges from 0 to 13; the record describes 13 as the worst score and zero as a healthy patient with no evidence of pneumonia. The assessments were to be made by one blinded central reviewer to minimize inter-observer variability.

As a continuous measure, CPIS retains the degree of change rather than reducing each participant's assessment to a yes-or-no outcome. Comparing group-level change can describe whether scores moved in different directions or by different amounts during the treatment period. The scale's stated direction matters when reading the values: lower CPIS values represent less severe scores, and a decrease from baseline is a negative change.

There are limitations to what this summary conveys. A mean change does not show the distribution of individual responses, and the registry's summary does not describe how missing daily assessments were handled. The endpoint also does not by itself answer every question about mortality, ventilation, microbiological response, or safety; those are addressed through separate outcomes in the registry record.

7. Results Posted in the Registry

• Amikacin Fosfomycin Inhalation Solution: mean -0.76 versus -0.88 on control; difference 0.12 (95% CI -0.98 to 1.22), standardized effect d = 0.04; z-test p = 0.831.

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.

Number of Days Free of Mechanical Ventilation From Day 1 Through Day 28

• 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:
  • Amikacin Fosfomycin Inhalation Solution: mean 9.80 versus 12.50 on control; difference -2.70 (95% CI -5.90 to 0.50), standardized effect d = -0.28; z-test p = 0.098.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Amikacin Fosfomycin Inhalation Solution and the control. The interval gives the range of effects that remain compatible with the data.

Number of ICU Days From Day 1 Through Day 28

• 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:
  • Amikacin Fosfomycin Inhalation Solution: mean 28.90 versus 26.20 on control; difference 2.70 (95% CI -1.39 to 6.79), standardized effect d = 0.22; z-test p = 0.196.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Amikacin Fosfomycin Inhalation Solution and the control. The interval gives the range of effects that remain compatible with the data.

Microbiological Response Rates in Patients Positive for Multi-drug Resistant Gram-negative Bacteria

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Amikacin Fosfomycin Inhalation Solution: 43.5% (10/23) versus 43.8% (7/16) on control; risk difference -0.3 percentage points (95% CI -31.9 to 31.4), risk ratio 0.99 (0.48–2.05); unadjusted two-proportion z-test p = 0.987.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Amikacin Fosfomycin Inhalation Solution and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several distinct aspects of the trial: time away from mechanical ventilation, ICU days, microbiological response, mortality, clinical cure, and relapse. The posted numerical results are limited to the first three of those categories. The remaining listed outcomes do not have numerical results reported in the registry record, so they cannot contribute a quantitative comparison in this interpretation.

Across the posted secondary comparisons, the point estimates do not all point in the same direction. The confidence intervals for the reported differences include zero, and the microbiological response comparison is also imprecise. This pattern does not resolve the uncertainty in the primary CPIS comparison. It also should not be compressed into a single overall verdict: the outcomes measure different things, use different scales, and may involve different participant subsets.

Secondary outcomes can help describe whether results are consistent across related measures, but they generally carry less weight than a prespecified primary endpoint. That is especially true when multiple outcomes are examined without a reported multiplicity adjustment. General explanation: as the number of statistical comparisons increases, the chance of at least one apparently notable result arising by chance can increase. An unadjusted p-value does not account for the full family of comparisons.

The registry does not report a hierarchy for testing the secondary outcomes, a multiplicity-control strategy, or full statistical analyses for these outcomes. The listed secondary comparisons should therefore be treated as descriptive evidence with uncertainty, rather than as a set of independent confirmatory tests. Their differing directions do not establish a consistent benefit or harm, and absence of numerical results for other listed outcomes should not be interpreted as a null finding.

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

• Composite Endpoint of Mortality and Clinical Cure
• Composite Endpoint of Mortality and Ventilator-free Days
• Number of Days Free of Mechanical Ventilation From Day 1 Through Day 28
• Number of ICU Days From Day 1 Through Day 28
• Microbiological Response Rates in Patients Positive for Multi-drug Resistant Gram-negative Bacteria
• Mortality From Day 1 Through Day 28
• Clinical Relapse Rate

9. Statistical Interpretation

10. Statistical Methods Explained

Continuous outcomes and group comparisons. The primary endpoint is continuous: each participant has a numerical CPIS change, and the registry presents least-squares mean summaries. The secondary ventilation-free and ICU-day outcomes are also continuous in the posted results and are summarized as means with standard deviations. A mean describes the central average; the standard deviation describes variation among observations. These are different quantities: variability among participants is not the same as uncertainty in the estimated group mean.

General explanation: A difference in means places two group averages on the same scale and gives a direction as well as a magnitude. The comparison is expressed as the inhaled combination group relative to placebo. A positive or negative estimate must be interpreted in light of the outcome's scale and how the comparison is defined. For CPIS, decreases from baseline are negative changes, while lower CPIS scores are described as less severe.

Least-squares means. The registry identifies the primary summary as a least-squares mean. In general, least-squares means are model-based group averages, often adjusted for terms in a statistical model. The registry record does not report the model specification or the adjustment terms, so the exact modeling procedure cannot be reconstructed from the summary. The daily assessments are described as contributing to the change-from-baseline summary over all days in the treatment period.

Standard errors and standard deviations. The primary arm summaries report standard errors, whereas the secondary continuous outcomes report standard deviations. In general, a standard error describes the precision of an estimate, such as a group mean; it is not a measure of the spread of individual observations. A standard deviation describes that spread. These measures should not be interchanged. The primary comparison's standard error and confidence interval are not listed as arm-level confidence limits in the record.

Confidence intervals. General explanation: a confidence interval expresses the range of values reasonably compatible with the data and the method used to construct it. For a difference, an interval that contains zero includes no difference as one possible value. An interval that also extends to values on either side of zero may be compatible with effects in either direction. It does not mean that every value in the interval is equally likely, and it is not a guarantee about an individual participant's outcome.

Unadjusted p-values. The reported p-values for the comparisons are unadjusted. General explanation: a p-value measures how unusual the observed data, or more extreme data, would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Because the record does not report multiplicity adjustment, these p-values should not be read as controlling the overall false-positive risk across all outcomes.

Binary outcome. The microbiological response endpoint is reported as participant counts at Day 14. The record lists 10 of 23 participants in the intervention group and 7 of 16 in the placebo group. Its comparison is expressed as a risk difference, with a confidence interval and an unadjusted p-value. General explanation: a risk difference compares the observed proportions directly, while a confidence interval describes uncertainty in that difference. The record also presents relative measures, but these summaries do not remove the uncertainty created by the small denominators.

Over-dispersion and distributions. General explanation: over-dispersion occurs when observed variability is greater than a model assumes. When that happens, a model that understates variability may report confidence intervals that are too narrow and p-values that are too small. The registry does not report whether over-dispersion was assessed or how any such issue was handled. For outcomes such as days, a mean and standard deviation do not show the shape of the distribution, including whether values cluster or are skewed.

Planning illustrations. The sample-size illustrations use the observed effects and stated planning assumptions; they are not the trial's original design calculations. General explanation: power is the chance, under a specified design and assumed effect, of detecting an effect under the chosen analysis when that effect is present. Planning estimates depend on assumptions about the effect, variability, allocation, significance level, and analysis. They should not be confused with the probability that the reported trial result is correct.

Analysis details and missingness. The registry identifies the primary population as MITT but does not describe the population definition or the handling of missing daily values. It reports no secondary analyses in the analysis listing, and no outcome-specific reported analyses are listed for the posted secondary outcomes. The statistical plan, model details, and interim analyses are not reported in the registry record. These absences limit how fully the reported summaries can be assessed, but they do not justify filling in unstated procedures.

11. Confidence Intervals and Precision

The primary mean difference is 0.12, with a 95% confidence interval from -0.981 to 1.221. Because the interval includes zero and extends to both negative and positive values, the estimate is compatible with more than one direction of group difference. Its breadth relative to the point estimate means the registry's summary does not pin down the size or direction of the underlying difference precisely. The unadjusted p-value is 0.831, which likewise does not indicate a clear separation between groups under the unadjusted comparison.

Confidence intervals describe uncertainty around an estimated group contrast, not the range of individual participants' scores. They also do not establish that two treatments are equivalent. Equivalence or non-inferiority would require a prespecified margin and an analysis designed for that question; such details are not reported in the registry record.

The secondary continuous comparisons also have intervals that include zero: the mean difference for days free of mechanical ventilation is -2.7, with a 95% confidence interval from -5.896 to 0.496; the mean difference for ICU days is 2.7, with a 95% confidence interval from -1.392 to 6.792. For microbiological response, the risk difference is -0.003, with a 95% confidence interval from -0.319 to 0.314. Those intervals indicate uncertainty in the corresponding contrasts, not certainty that there is no difference.

The primary arm summaries are reported with standard errors of 0.403 and 0.391. Standard errors concern the estimated means, while the comparison interval conveys uncertainty in the contrast. The record does not report model details that would allow a fuller assessment of interval construction.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning scenarios based on the observed effect, not the trial's original design assumptions. For the continuous outcomes and the binary response outcome, the figures are participants per arm. The record's stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each scenario uses the stated fraction of the observed effect. The time-to-event convention would be total events, but the reported outcomes with planning figures in this record are not time-to-event outcomes.

The 80% power column gives the illustrative participants per arm for a design with an 80% chance of detecting the assumed effect under those planning assumptions. The 90% power column gives the corresponding per-arm requirement for a design with a 90% chance. These are prospective design calculations under assumptions, not a measure of how much power the completed trial had after its results were observed; this is not observed power.

The rows planning for 100%, 75%, and 50% of the observed effect show how the illustrative sample size changes when the assumed target effect is reduced. Smaller effects are harder to distinguish from random variation, so they require more participants under otherwise unchanged assumptions. The values are sensitive to the observed effect used as the starting point and to the statistical assumptions. They should not be interpreted as evidence that the original trial was planned around these values. The original sample-size justification is not reported in the registry record.

These planning figures are aids for understanding the scale of a hypothetical future design, not results about the trial groups. They do not correct for missing data, outcome multiplicity, or other design features unless those are explicitly included in the assumptions; such adjustments are not stated in the registry's planning description.

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 = 0.120; pooled standard deviation σ = 3.346.
2. n = 2 × (1.96 + 0.842)² × 3.346² / 0.120² = 12,201.5, rounded up to 12,202 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 <- 0.12                      # observed difference in means
sigma <- 3.34556348019284                     # 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(1969799)
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 = 12,202 (80% power), 16,335 (90% power)
 75% of observed effect: n per arm = 21,692 (80% power), 29,039 (90% power)
 50% of observed effect: n per arm = 48,807 (80% power), 65,338 (90% power)
power.t.test: 12202.5 
Simulated power at n = 12,202 per arm: 0.800 (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 lists one primary endpoint and multiple secondary outcomes. It does not report a multiplicity strategy for controlling the chance of false-positive findings across those outcomes. The comparison p-values available for the primary and selected secondary results are unadjusted. They therefore address their individual comparisons without an indicated correction for the set of outcomes. General explanation: when many hypotheses are tested, interpreting each unadjusted p-value as though it were the only test can overstate the strength of evidence.

The record does not report interim analyses or stopping rules. It also does not give the trial's full statistical analysis plan, detailed model specifications, or a description of how missing measurements were handled. For the primary endpoint, daily assessments were planned over the treatment period, but the registry summary does not state how incomplete daily records, withdrawals, or other missing values entered the reported least-squares means.

The primary population is labeled MITT, but the registry record does not expand the label or specify its inclusion rules. The primary endpoint arm counts are 71 in each group, while the safety denominators are 71 and 72. These reported denominators should be kept distinct; the record does not explain the difference. The microbiological response analysis includes 23 participants in the intervention group and 16 in the placebo group, indicating that its posted comparison concerns a smaller subset than the primary summaries. Further details about selection into that subset are not reported in the registry record.

Seven secondary outcomes are listed, while numerical results are posted for only selected outcomes. The registry record does not report numerical findings for the other listed secondary endpoints. Missing outcome reporting should not be interpreted as evidence of no effect, and absent methodological details should not be replaced with assumptions about the protocol.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: septic shock (8.3%), acute respiratory failure (4.2%), endotracheal intubation complication (4.2%), sepsis (2.8%), cardiac arrest (2.8%).

For serious adverse events, the registry reports 28 affected participants among 71 at risk in the Amikacin Fosfomycin Inhalation Solution group and 27 among 72 at risk in the Aerosolized Placebo group. For other adverse events, the reported counts are 54 of 71 and 58 of 72, respectively. These are counts of participants recorded with events in each category, not adjusted comparisons of risk.

The registry lists serious-event terms including septic shock at 8.3%, acute respiratory failure at 4.2%, endotracheal intubation complication at 4.2%, sepsis at 2.8%, cardiac arrest at 2.8%, and pneumonia with a new pathogen than baseline at 2.8%. The record does not state whether these terms are mutually exclusive, so they should not be read as a partition of all serious events.

Death counts are not reported in the registry record. The posted adverse-event figures do not by themselves establish whether an event was caused by the study treatment. They describe recorded events in the trial groups and should be interpreted alongside the study's design and the limits of the available safety detail.

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

The primary result is an estimate of the difference between groups in mean CPIS change over the 10 day treatment period. The point estimate is 0.12 and its 95% confidence interval spans values on either side of zero. This means the posted results do not clearly distinguish the groups on the primary endpoint, while still leaving uncertainty about the size and direction of the difference.

The result does not prove that the groups are identical, nor does it establish equivalence. A nonsignificant unadjusted comparison is not the same as evidence that any difference is exactly zero. The confidence interval helps show why: it includes zero but also a range of nonzero possibilities. The record does not report an equivalence or non-inferiority framework.

Nor does the primary result settle every outcome relevant to the trial. Secondary outcomes address mechanical ventilation, ICU days, microbiological response, mortality, clinical cure, and relapse. Only selected secondary outcomes have numerical results reported, and those available comparisons also remain uncertain. The serious adverse-event counts describe events observed in each group but do not demonstrate causality.

These findings apply to the trial population and measures described in the registry record: mechanically ventilated patients with Gram-negative pneumonia receiving intravenous antibiotics, randomized to inhaled combination treatment or aerosolized placebo. The record does not provide sufficient detail to generalize beyond that setting or to reconstruct all eligibility and analysis procedures. No treatment recommendation follows from these registry summaries alone.

17. Why This Trial Matters Statistically

This trial is statistically informative because its primary outcome is a repeated clinical score summarized across a defined treatment period, rather than a single measurement at one time. The daily CPIS assessments and use of a blinded central reviewer address the possibility that subjective scoring may vary between assessors. The registry also makes the scale direction explicit, which is essential when interpreting changes from baseline.

The comparison illustrates why a point estimate and its precision must be read together. The estimated difference is close to zero, but its confidence interval is wide enough to include values in either direction. A reader should not equate a lack of statistical separation with proof of no effect; the interval indicates that the estimate remains uncertain.

The trial also reports outcomes that reflect different dimensions of illness and care, including ventilator-free days, ICU days, and microbiological response. These measures do not necessarily move together, and they should not be treated as substitutes for the primary endpoint. Their unadjusted status and the lack of a reported multiplicity plan make disciplined interpretation particularly important.

Finally, the record distinguishes trial results from planning illustrations based on observed effects. Those illustrations can show how assumed effect size affects hypothetical sample requirements, but they do not explain the original design or provide observed power. Keeping those purposes separate is important when using registry data to understand both evidence and future study planning.

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.

Several trial-specific limitations are apparent from the registry record. The detailed statistical analysis plan, original sample-size justification, interim analyses, missing-data methods, and model specification are not reported. As a result, the least-squares mean analysis cannot be fully reconstructed from the posted summaries, and the handling of incomplete daily CPIS assessments is unclear.

The primary population is labeled MITT without a definition in the record. The primary endpoint summaries use 71 participants per group, while the safety summaries use 71 in the intervention group and 72 in placebo. The registry does not explain the denominator difference. The microbiological response outcome is reported for a smaller subset, and the record does not provide further detail about the subset's selection or analysis.

Numerical results are not reported for several listed secondary outcomes, including the mortality and clinical cure composite, the mortality and ventilator-free-days composite, mortality through Day 28, and clinical relapse. Their omission from the posted results prevents quantitative assessment of those endpoints; it is not evidence of no difference.

Available comparison p-values are unadjusted, and no multiplicity strategy is reported. The primary estimate's confidence interval is broad and includes zero. For the secondary outcomes, the available summaries also leave uncertainty. Finally, the registry record does not provide enough information to assess all potential limitations of outcome measurement, adherence, or protocol implementation beyond the stated blinded central CPIS reviewer and treatment schedules.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia — NCT01969799.
• Registry record last updated 2017-07-02; status last verified 2016-03.
• Results first posted 2017-07-02.
• 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

NCT01969799 is a completed, randomized, quadruple-masked, parallel-group phase 2 study sponsored by Cardeas Pharma. It enrolled 143 mechanically ventilated patients with Gram-negative pneumonia. Participants received aerosolized amikacin and fosfomycin or aerosolized placebo, alongside intravenous antibiotics as described in the trial summary.

The primary endpoint was change from baseline in CPIS over the 10 day treatment period. The reported mean difference was 0.12, with a 95% confidence interval from -0.981 to 1.221 and an unadjusted p-value of 0.831. The interval includes zero and leaves the direction and size of the group difference uncertain. Selected secondary outcome and adverse-event summaries are also posted, while numerical results for other listed secondary endpoints are not reported in the registry record.