Pharmacodynamic Evaluation of Intranasal Nalmefene: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacodynamic Evaluation of Intranasal Nalmefene (NCT04828005), a randomized phase 1 study. The primary outcome is Change in Minute Ventilation.

2. Clinical Question

The study concerns pharmacodynamic effects: the effects of the drugs and their mechanisms of action within the body. Its comparison is between two intranasal treatments in a controlled research setting, rather than an assessment of clinical outcomes in a patient population. Minute ventilation is the primary measure, expressed in L/min, and the endpoint records its change from the opioid-induced nadir at the stated timeframe.

The posted arm summaries show a mean change of 5.744 for nalmefene and 3.432 for naloxone. The unadjusted mean difference is 2.312, with a 95% confidence interval from 0.599 to 4.025. These figures describe the posted endpoint results and their statistical uncertainty. They do not establish how the treatments compare on outcomes beyond those measured in this study, and the registry record does not report a clinical threshold for interpreting the size of the difference.

3. Trial Design

This was a phase 1, randomized, open-label crossover study of intranasal nalmefene and intranasal naloxone. The registry record gives the title as a two-part study of pharmacodynamic effects in healthy volunteers under steady-state opioid agonism. It lists enrollment of 84 and a completed status. The recorded start date is 2021-03-30 and the primary completion date is 2022-03-14.

In a crossover design, participants receive more than one treatment during the study, so each participant can contribute observations under different treatments. This general design can support within-participant comparisons, but interpretation depends on details such as treatment order, timing, and how the analysis accounts for repeated observations. The registry record does not report the treatment sequence, period structure, washout arrangements, or the specific model terms used for the sponsor’s mixed-model analysis.

The study is described as open label, meaning masking was not used. The registry lists randomized allocation, but does not report the randomization procedure or allocation ratio. It records the nalmefene spray as 3mg, 1 spray, and the naloxone spray as 4mg, 1 spray. The registry record does not report the original sample-size justification or the intended power for the trial.

Although enrollment is recorded as 84, the primary outcome summaries list 59 participants for naloxone and 60 for nalmefene. These are outcome-specific arm counts; the registry record does not explain the difference between enrollment and the counts contributing to these summaries. The participant analysis population and reasons for unavailable outcome data are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Part 1 Setup and Part 1 Extension Setup were Ventilation Models only; outcome measures were not collected in Part 1. Part 2 participant flow was only reported as one group (i.e., it is not possible to show how many participants received each intervention).

Part 1 Setup: 1st Treatment (1 Day)

Part 1 Setup: Washout (4 Days)

Reasons for not completing this period:

Part 1 Setup: 2nd Treatment (1 Day)

Part 1 Extension: 1st Treatment (1 Day)

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Change in Minute Ventilation, measured over 5 minutes.

The primary endpoint is the change in minute ventilation from the opioid-induced nadir, measured at 5 minutes and expressed in L/min. Minute ventilation describes the amount of air moved in and out of the lungs over time. In this study, measuring change from the nadir focuses the endpoint on the increase or decrease relative to the lowest point reached under opioid agonism, rather than on an absolute ventilation value alone.

The registry reports a mean for each treatment and uses standard errors to describe the precision of those arm means. The naloxone mean is 3.432, with a standard error of 0.612, among 59 participants. The nalmefene mean is 5.744, with a standard error of 0.624, among 60 participants. The unadjusted difference between the means is 2.312 L/min in the direction of a larger mean change with nalmefene.

As a general statistical point, a continuous endpoint can retain information about the range of observed measurements rather than reducing results to categories. The choice of a five-minute measurement makes the primary question specific to that time point; it does not describe the entire response over time. The registry record does not report a threshold that would define a clinically important difference in minute ventilation.

7. Results Posted in the Registry

• Intranasal Nalmefene: mean 5.74 versus 3.43 on control; difference 2.31 (95% CI 0.60 to 4.02), standardized effect d = 0.48; z-test p = 0.008.

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.

Maximum Change in Minute Ventilation

• 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:
  • Intranasal Naloxone: mean 5.80 versus 6.80 on control; difference -1.00 (95% CI -2.02 to 0.02), standardized effect d = -0.35; z-test p = 0.054.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intranasal Naloxone and the control. The interval gives the range of effects that remain compatible with the data.

Change in Minute Ventilation

• 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:
  • Intranasal Naloxone: mean 2.14 versus 2.71 on control; difference -0.57 (95% CI -2.25 to 1.11), standardized effect d = -0.12; z-test p = 0.505.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intranasal Naloxone and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists seven secondary outcomes, while two secondary result summaries are included in the record. They cover maximum change in minute ventilation and change in minute ventilation at a later stated timeframe. The available summaries do not provide a complete set of results for every listed secondary outcome, so the overall secondary-outcome evidence is only partly represented in the registry record.

Across the two posted summaries, the numerical contrasts point in the same direction as the primary mean comparison, with larger mean values in the nalmefene summaries. Their inferential precision is not uniform: one secondary interval comes close to including zero, while the other spans zero more broadly. These outcomes concern different measures or timeframes, so they should not be treated as repeated measurements of one identical effect. The primary result remains the designated primary endpoint and has its own stated timepoint and analysis.

Unadjusted secondary findings carry less weight when multiple outcomes are examined. As a general statistical principle, looking across many outcomes creates more opportunities for a result to appear noteworthy by chance. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. It also does not report sponsor analyses for the two secondary summaries. Consequently, the secondary results are best regarded as supporting descriptive context rather than independent confirmatory evidence.

The endpoint naming and units in the registry should be read as recorded. In particular, the maximum-change result is labelled with unit ng/mL, while its title refers to minute ventilation; the record does not explain this labeling. No inference should be made from the discrepancy beyond noting that the registry’s endpoint label and unit are as posted.

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

• Maximum Change in Minute Ventilation
• Time to Maximum Change in Minute Ventilation
• Change in Minute Ventilation
• Change in Minute Ventilation
• Change in Minute Ventilation
• Change in Minute Ventilation
• Change in Minute Ventilation

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a continuous primary endpoint summarized by its mean and standard error. The comparison is a mean difference. Such a contrast describes the separation between the two reported group means in the measurement’s original units, L/min. The reported difference of 2.312 is oriented as nalmefene minus naloxone, so a positive value indicates a larger mean in the nalmefene arm summary.

What does a standard error describe?

As a general statistical explanation, a standard error describes uncertainty in an estimated quantity, such as a sample mean. It is not the same as the spread of individual observations: a standard deviation describes variation among observations, while a standard error concerns the precision of an estimate. The primary outcome summaries report standard errors of 0.612 and 0.624 for the arm means. These values help describe precision but do not show the full distribution of individual measurements.

A mean difference and its standard error are used to characterize uncertainty in the contrast. Here, the registry record gives a confidence interval directly, so no interval needs to be reconstructed from the arm-level standard errors. Because the trial is a crossover, an analysis that uses participant-level observations may account for within-participant association. The simple posted-summary recalculation does not encode those design features unless they are reflected in the inputs, and the record does not describe such an adjustment for this recalculation.

How should the p-value be read?

As a general statistical explanation, a p-value measures how compatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The primary unadjusted p-value is 0.008. It should be read alongside the effect estimate and confidence interval, not in isolation.

The p-value is labelled unadjusted. That matters when several outcomes or comparisons are considered, because the chance of at least one apparently unusual result can increase across repeated testing. The registry lists eight outcome measures and seven secondary outcomes, but does not report a multiplicity strategy. The absence of a stated adjustment means the posted p-value should not be interpreted as a family-wise confirmatory result.

Why does the crossover design matter?

As a general design principle, crossover studies can compare treatments within participants, which may reduce variation associated with stable differences between people. At the same time, analysis must account for the repeated measurements and may need to consider period or sequence effects, depending on the protocol. The registry record identifies a crossover model and a sponsor mixed-model analysis, but does not report the model specification, covariance structure, sequence terms, or period terms. Those details are not reported in the registry record, so the sponsor analysis cannot be independently reconstructed from the posted summary.

The primary recalculation is an unadjusted comparison of posted summary statistics. It is useful for describing the two means and their simple contrast, but it should not be confused with the sponsor’s design-aware analysis. There is no recorded discrepancy flag for this endpoint. Even so, the methods are not identical in what they use, and the sponsor’s reported mixed-model result remains a separate analysis.

What does the non-inferiority label establish?

The registry reports a mixed models analysis identified as non-inferiority, with p < 0.001. A non-inferiority analysis generally asks whether a treatment is no worse than a comparator by more than a prespecified margin. That is a general explanation; the margin, null hypothesis, analysis population, and supporting estimate are not reported in the registry record. Without those details, the label and p-value alone do not show the size of the treatment contrast or allow the non-inferiority analysis to be evaluated fully.

Overall, the primary mean difference, confidence interval, and unadjusted p-value describe the posted summary contrast. They do not reveal the full statistical model or replace the trial’s sponsor analysis. The registry record leaves important analysis details unspecified, including the original sample-size justification, missing-data handling, analysis populations, and multiplicity approach.

11. Confidence Intervals and Precision

The 95% confidence interval for the primary mean difference is 0.599 to 4.025 L/min. The point estimate is 2.312 L/min. The interval gives a range of values compatible with the posted unadjusted comparison under its statistical assumptions; it is not a range containing 95% of individual participant measurements, nor does it mean there is a 95% probability that the true effect lies in this particular interval.

Both ends of the primary interval are above zero. This indicates that the posted unadjusted comparison is more precise than one whose interval spans zero, while still allowing a range of possible mean differences. The lower and upper limits are separated enough that the estimate does not identify a single exact effect. The registry record does not report a threshold for clinical importance, so the interval cannot determine whether values within it correspond to meaningfully different consequences.

As a general explanation, confidence intervals reflect both the observed estimate and its uncertainty under the analysis. More precise estimates tend to have narrower intervals; less precise estimates tend to have wider ones. Precision is affected by the amount of information and by variation in the data, as well as by features of the analysis. In a crossover study, handling the relationship between repeated measurements can affect uncertainty. The registry does not provide enough model detail to assess how the sponsor’s mixed-model uncertainty compares with the simple unadjusted interval.

The interval should therefore be interpreted as precision for this specific primary contrast and timeframe, not as certainty about all pharmacodynamic effects or about outcomes outside the study. It also does not address potential bias from missing data, open-label conduct, or the applicability of results to populations beyond the healthy volunteers described in the record.

12. Planning a Similar Trial: Sample Size

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

The planning illustrations give participants per arm for 80% power and participants per arm for 90% power. They use the observed effect as a reference and consider planning for 100%, 75%, or 50% of that observed effect. For the primary endpoint, planning for 100% of the observed effect gives 67 participants per arm for 80% power and 90 participants per arm for 90% power. Planning for 75% gives 119 participants per arm for 80% power and 159 participants per arm for 90% power. Planning for 50% gives 267 participants per arm for 80% power and 358 participants per arm for 90% power.

The assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. These are planning illustrations, not the trial’s original design assumptions; the original sample-size justification is not reported in the registry record. The figures are participants per arm, not total participants and not total events.

In plain language, 80% power means that a design with the stated assumptions would have an 80% chance of detecting the specified effect at the stated significance level if that effect were the true one. The 90% column describes a higher chance of detection under the same assumptions and therefore generally requires more participants. Smaller effects are harder to distinguish from random variation, so the illustrations require more participants when the target is a smaller fraction of the observed effect. These values are not observed power.

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 = 2.312; pooled standard deviation σ = 4.767.
2. n = 2 × (1.96 + 0.842)² × 4.767² / 2.312² = 66.7, rounded up to 67 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 <- 2.312                      # observed difference in means
sigma <- 4.76707399871565                     # 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(4828005)
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 = 67 (80% power), 90 (90% power)
 75% of observed effect: n per arm = 119 (80% power), 159 (90% power)
 50% of observed effect: n per arm = 267 (80% power), 358 (90% power)
power.t.test: 67.7 
Simulated power at n = 67 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports a sponsor analysis described as a mixed models analysis and labels it non-inferiority. It gives p < 0.001 for the listed analysis, but no effect estimate, confidence interval, non-inferiority margin, or detailed model specification. The result therefore cannot be translated into a numerical treatment contrast from the registry record alone.

The posted primary summary also supports an unadjusted recalculation: the mean difference is 2.312 L/min, with a 95% confidence interval from 0.599 to 4.025 and an unadjusted p-value of 0.008. This recalculation is based on the posted summary statistics and is not the same as the sponsor’s mixed-model analysis. A crossover analysis can account for within-participant structure, while the simple summary comparison does not demonstrate how that structure is modeled.

The registry record does not flag a discrepancy between the posted result and the recalculation. The sponsor analysis should therefore be read as a separate design-specific analysis, not as a numerical confirmation that can be directly compared from the information recorded. The registry’s missing details prevent assessment of how the non-inferiority question was specified or how its conclusion relates quantitatively to the unadjusted mean difference.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary outcome and seven secondary outcomes. It does not report whether the statistical plan controlled the overall false-positive risk across multiple outcomes, which outcomes were included in any testing hierarchy, or whether particular secondary analyses were exploratory. Multiplicity handling is therefore not reported in the registry record. The primary result can be interpreted as the designated primary comparison, while unadjusted secondary findings deserve more caution when considered collectively.

The record reports outcome-specific participant counts, but does not explain why the primary arm summaries include 59 participants for naloxone and 60 for nalmefene, while enrollment is listed as 84. The secondary summaries have their own outcome counts. Reasons for missing measurements, exclusions, withdrawals, or differences in analysis populations are not reported in the registry record. The proportions of participants with missing outcome data cannot be evaluated from the information recorded.

The registry identifies a randomized crossover design and a sponsor mixed-model analysis, but does not describe the analysis population, inclusion criteria for the analysis, handling of missing observations, or assumptions used by the model for incomplete data. It does not report whether the primary analysis followed an intention-to-treat, per-protocol, or other population definition. These omissions limit evaluation of whether the posted summaries represent all randomized participants or a subset defined by outcome availability.

The registry’s non-inferiority analysis is also missing details needed for full appraisal: the non-inferiority margin, the exact estimand, the model specification, and the analysis population are not reported in the registry record. Those details matter because non-inferiority conclusions depend on the margin and on how the analysis population and missing data are handled. The posted p-value alone does not supply that information.

These reporting gaps do not change the arithmetic of the posted summaries, but they constrain what can be concluded about robustness. They also make it difficult to reconcile a simple unadjusted recalculation with the trial’s design-aware sponsor analysis.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 61 participants at risk in the nalmefene group and 60 in the naloxone group. Serious adverse events affected 0 participants in each group. The record lists 0 deaths in both groups. No serious adverse event terms are listed.

Other adverse events are recorded for 56 participants at risk in the nalmefene group and 52 participants at risk in the naloxone group. These are counts for other adverse events, not serious adverse events. The registry does not provide event types or severity details for these other events in the information recorded.

These figures describe reported events within the registry record and should not be treated as a complete comparative safety assessment. The record does not describe the event collection methods, exposure duration, follow-up completeness, or whether participants could contribute events under both treatments in the crossover. The serious-event counts are zero in both groups, but the posted counts alone cannot establish that serious risks are absent or compare safety beyond the reported observation.

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

The posted primary results show a larger mean change in minute ventilation for intranasal nalmefene than for intranasal naloxone at 5 minutes after the opioid-induced nadir. The unadjusted mean difference is 2.312 L/min, and its 95% confidence interval is 0.599 to 4.025. This describes the observed contrast and its statistical precision under the simple comparison summarized in the record.

The result does not by itself establish clinical importance. The registry record does not report a threshold for a clinically important change, and the study evaluates a pharmacodynamic measure in healthy volunteers under steady-state opioid agonism. It does not establish how the result applies to people with a clinical condition, to different treatment settings, or to outcomes not measured in the study.

Nor does the primary comparison describe the full time course of response. The endpoint is specifically measured at 5 minutes, while the registry lists other outcomes that address different measures or timeframes. The posted secondary results are incomplete relative to the outcomes listed, and no multiplicity adjustment is reported.

The registry’s sponsor analysis is identified as a mixed-model non-inferiority analysis, but the record omits its estimate, interval, margin, and detailed model. That analysis cannot be fully interpreted or reconciled numerically with the unadjusted summary comparison. In addition, the registry does not report the original sample-size justification, the analysis population, or missing-data procedures.

Accordingly, the narrow statistical conclusion is that the posted primary summaries favor a larger mean change with nalmefene at the stated measurement time, with an unadjusted confidence interval that excludes zero. This does not settle questions about clinical meaning, safety beyond the reported adverse-event counts, or applicability beyond the studied setting.

18. Why This Trial Matters Statistically

This trial illustrates why an effect estimate, a confidence interval, and a p-value answer different questions. The estimate gives the scale and direction of the primary mean contrast; the confidence interval describes its uncertainty; and the p-value summarizes compatibility with a null model under the stated unadjusted calculation. None of these alone establishes clinical importance.

The crossover design also highlights the importance of matching the analysis to the design. Within-participant comparisons can use information from repeated observations, but the model and its assumptions need to be reported for readers to judge how the design was handled. The registry identifies a sponsor mixed-model analysis while also making summary statistics available for a simpler comparison. Those analyses are related but not interchangeable.

Multiplicity matters because several outcomes are listed, and only a subset has results in the record. Without a reported strategy for controlling or organizing multiple tests, secondary findings should be treated more cautiously than the designated primary result. Missing details about analysis populations and incomplete outcome data further affect how confidently the summaries can be generalized to the randomized study population.

Finally, planning calculations based on the observed effect show how sample-size requirements change when the target effect is smaller or the desired power is higher. These illustrations are useful for understanding design trade-offs, but they do not reveal the assumptions behind the original trial design. Separating planning illustrations from the trial’s actual design justification is essential for a careful statistical reading.

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.

Several limitations specific to this record constrain interpretation. The trial is open label, so masking was not used. The registry does not describe how this design feature was addressed in outcome assessment or analysis. The study is a crossover, but the treatment sequence, period structure, washout arrangements, and handling of possible period or sequence effects are not reported in the registry record.

The sponsor’s mixed-model non-inferiority analysis is not fully documented. Its estimate, confidence interval, non-inferiority margin, analysis population, and model specification are not reported. The simple unadjusted summary comparison does not reproduce those design-specific details. This makes it difficult to evaluate how the sponsor analysis relates quantitatively to the posted primary contrast.

The registry lists enrollment of 84, while the primary arm summaries have outcome counts of 59 and 60. It does not explain the difference or report reasons for missing measurements and exclusions. The analysis population and missing-data approach are not reported, limiting assessment of potential selection effects. The registry also does not give the original sample-size rationale or the multiplicity plan.

Only two secondary result summaries appear despite seven secondary outcomes being listed. The record does not report sponsor analyses for those secondary summaries, and one secondary endpoint’s title and unit do not appear readily aligned as recorded. These issues make the secondary evidence incomplete and harder to interpret. Finally, the study concerns healthy volunteers under steady-state opioid agonism, and the registry does not establish applicability to other populations or settings.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Pharmacodynamic Evaluation of Intranasal Nalmefene — NCT04828005.
• Registry record last updated 2025-07-14; status last verified 2025-06.
• Results first posted 2025-07-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry describes a completed phase 1 randomized, open-label crossover study of intranasal nalmefene and intranasal naloxone in healthy volunteers under steady-state opioid agonism. Enrollment is listed as 84. The primary endpoint is mean change in minute ventilation from the opioid-induced nadir at 5 minutes.

The posted primary means are 5.744 for nalmefene and 3.432 for naloxone. The unadjusted mean difference is 2.312 L/min, with a 95% confidence interval from 0.599 to 4.025 and an unadjusted p-value of 0.008. The registry also reports a mixed-model non-inferiority analysis with p < 0.001, but does not provide its estimate or key methodological details.

Interpretation is limited by unreported design and analysis details, including the original sample-size justification, missing-data handling, analysis populations, and multiplicity approach. The posted adverse-event record reports no serious adverse events or deaths in either group.