Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies (NCT05279898), a randomized na study. The primary outcome is Increase in Plasma IL-6 Levels.

2. Clinical Question

The study was randomized, single-masked, and parallel-group, with planned enrollment of 70. Its stated aims also include reducing perioperative neurocognitive dysfunction, supporting hemodynamic stability and reducing vasopressor use in the operating room, and reducing postoperative pain and opioid consumption. Those aims are not themselves evidence of an observed treatment effect. Results for the primary comparison and the listed secondary outcomes are not reported in the registry record.

3. Trial Design

PATHFINDER II is a randomized, single-masked, parallel-group study sponsored by Beth Israel Deaconess Medical Center. The registry lists the study as completed and gives enrollment of 70. Its phase is listed as NA. The registry dates are start on 2023-02-28 and primary completion on 2024-06-30.

The two groups are an EEG-guided MMGA bundle and standard-of-care control. In the MMGA description, the bundle includes routine anesthetic induction, a bilateral pectoro-interfascial block using ropivacaine after induction and before incision, and ketamine and remifentanil. The description also begins to list dexmedetomidine but does not provide a complete protocol. The control description says EEG monitoring was blinded and did not guide anesthesiologists; patients received routine intraoperative anesthesia practice. It also describes postoperative propofol, with or without sevoflurane, and a standard pain-management protocol. The full dosing and treatment details are not reported in the registry record.

Random allocation is intended to make treatment groups comparable on average, while a parallel design assigns participants to one group rather than describing a crossover. The registry lists single masking but does not identify who was masked. It does not report the allocation procedure, concealment details, or the planned analysis population. The stated planned enrollment should not be mistaken for the number with valid samples at each primary-outcome time point: the registry says analyzed counts differ because of missing or inadequate biospecimens.

The study lists eight outcome measures and six secondary-outcome topics: opioid consumption, pain scores, burst suppression, postoperative delirium, cognitive function, and total vasopressor dose as a measure of hemodynamic stability. Numerical results for these outcomes are not reported in the registry record. The record also does not report a sample-size justification or a detailed statistical analysis plan.

4. Participant Flow and Accounting

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

Before assignment: There were no washout, run-in, or lead-in phases. All enrolled participants were randomized in a 1:1 ratio to either the EEG-guided multimodal general anesthesia (MMGA) group or the standard care group without pre-assignment exclusions.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of participants analyzed at each time point differs from the number originally assigned due to missing or inadequate biospecimen samples for IL-6 and NFL measurements at baseline and postoperative days 1 and 2. Participants without valid samples at a given time point were excluded from that specific analysis.

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.

Population: One participant's baseline information is missing in the intervention group, and one participant's ethnicity data is missing in the control group

6. Primary Endpoint

The registry lists the primary outcome as Increase in Plasma IL-6 Levels, measured over Baseline, postoperative day 1, and postoperative day 2.

The primary outcome is titled “Increase in Plasma IL-6 Levels.” The registry describes measuring plasma interleukin-6 at baseline, postoperative day 1, and postoperative day 2, calculating the change from baseline at each postoperative time point, and comparing those changes between study groups. The outcome is a continuous measure, summarized as a mean with standard deviation.

In general, a continuous measure retains information about the size of each observed value rather than reducing observations to categories. A change-from-baseline comparison focuses on how the measured concentration differs from a participant’s starting measurement. Comparing those changes between randomized groups addresses whether the pattern of change differs between the assigned strategies. The mean describes the central value in a group; the standard deviation describes how spread out individual measurements are around that mean.

IL-6 is the laboratory measure specified by the registry as the primary outcome. The registry’s stated rationale is to assess changes in IL-6 over the perioperative time points; a more detailed justification for selecting this biomarker is not reported in the registry record. No numerical group means, changes, between-group estimates, confidence intervals, or statistical tests are reported, so the direction and precision of the primary comparison cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary comparison ask?

The registry defines the primary outcome as an increase in plasma IL-6 and describes measuring it at baseline, postoperative day 1, and postoperative day 2. It says that change from baseline is calculated at each postoperative time point and compared between groups. In general, a change score is the later measurement interpreted relative to the participant’s baseline measurement. A between-group comparison of changes asks whether the average pattern differs between the assigned strategies, rather than merely asking whether measurements changed over time within either group.

The outcome is continuous and is specified as a mean with standard deviation. In general, the mean is a summary of the center of the observed values, while the standard deviation describes their variability. These summaries do not show the full shape of a distribution, and they do not by themselves provide a between-group effect estimate or its precision. The registry record does not report the group summaries or the method used to estimate the primary comparison.

How should uncertainty be understood?

General explanation: an estimate is a result calculated from the observed participants, while its uncertainty reflects that another sample from the same underlying process could yield a different estimate. A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but precision alone does not establish whether an effect is important. The registry record does not report a confidence interval, standard error, or p-value for the primary outcome.

A p-value is conditional on a statistical model and a null hypothesis. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. Since no primary-outcome test result is reported, no significance assessment can be made from this record.

Why does the design matter?

Randomization assigns participants to groups by chance. As a general principle, this can reduce systematic differences between groups at the start of a study, although it does not ensure identical groups in a particular trial. A parallel-group design compares groups that remain assigned to their respective strategies. The registry identifies this study as randomized and parallel-group. It also lists single masking, but does not say who was masked or provide details about the masking procedure.

The registry describes a comparison of an EEG-guided MMGA bundle with standard care, rather than a comparison of one isolated drug with another. The intervention description includes multiple anesthetic components and a postoperative analgesic approach. As a general principle, a bundled strategy estimates the contrast between the assigned strategies as a whole; it does not by itself identify the contribution of each component. The registry does not report a component-specific analysis.

How should multiple time points and outcomes be considered?

The primary outcome is described at two postoperative time points, and the registry lists multiple secondary outcomes. In general, making several statistical comparisons creates a multiplicity issue: the chance of obtaining at least one apparently noteworthy result can increase when many tests are considered. Methods such as prespecified outcome hierarchies or adjustment procedures can address this concern, but the registry record does not report a multiplicity strategy or a detailed testing plan. It is not possible to determine from the record whether analyses were prespecified in a protocol or how results across time points were intended to be interpreted.

The registry lists eight outcome measures and zero analyses. The absence of posted analyses means there are no reported estimates to evaluate across the primary or secondary outcomes. The number of outcome measures alone does not reveal how many statistical tests were conducted or how results were selected for reporting.

What is the role of the planning illustration?

The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. It is explicitly a planning illustration based on an observed effect, not the trial’s own design justification. A planning calculation estimates the sample size needed under specified assumptions; it does not show the probability that a completed study has detected an effect, and it is not observed power. The registry record does not report the trial’s own sample-size justification. It also does not report the numerical planning outputs in the information available for interpretation.

In general, a planning result depends on assumptions about the target effect, variability, statistical error rate, allocation, and analysis. If those assumptions differ from the actual study conditions, the planning calculation may not describe the precision achieved in the completed study. No new sample-size calculation can be inferred from the registry description.

What analysis details remain unknown?

The registry does not report the statistical model, covariate adjustments, treatment of outliers, transformations, confidence-interval method, or a detailed analysis population for the primary endpoint. These choices can affect an estimate and its uncertainty. They should not be guessed from the randomized design or from the outcome’s mean-and-standard-deviation summary.

General explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a model does not accommodate that variability, its uncertainty estimates may be too small. Whether over-dispersion is relevant depends on the outcome and analysis; the registry does not report a model for the IL-6 comparison, so no trial-specific assessment is possible.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome covers change from baseline at postoperative day 1 and postoperative day 2. The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. A separate estimate at each time point can be informative, but interpreting multiple tests raises a general multiplicity concern. The registry record does not report whether a primary time point was designated as most important, whether an adjustment was planned, or how evidence across time points was to be combined.

The record lists six secondary-outcome topics and eight outcome measures overall. It does not report a multiplicity procedure, a hierarchy for testing outcomes, or a complete statistical analysis plan. It also reports zero analyses, so there are no posted outcome estimates to assess.

For the primary outcome, the registry states that the number analyzed at each time point differs from the number originally assigned because IL-6 and NFL biospecimens were missing or inadequate. Participants without valid samples at a time point were excluded from that time-point analysis. The number with valid IL-6 specimens at each time point, the reasons for missing or inadequate samples by group, and any additional missing-data methods are not reported in the registry record.

The record does not specify whether the primary analysis followed an intention-to-treat principle, used another analysis population, or included any imputation. Because sample availability may vary by time point, the analyzed population may not be the same for each comparison. The registry’s safety denominators should not be treated as primary-outcome analysis counts.

11. 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 0% reporting threshold.

The registry reports serious adverse events for 33 participants at risk in the MMGA group and 34 participants at risk in the standard-of-care control group. It records zero serious adverse events in each group and zero deaths in each group. It also records zero other adverse events in both groups among those at risk. No serious adverse-event terms are listed.

These figures are descriptive counts from the registry record. They do not establish that no adverse events occurred outside the categories or reporting periods captured in this record. The safety follow-up period, event definitions, collection procedures, and any assessment of differences between groups are not reported in the registry record. The at-risk counts are safety figures; they do not establish the number with valid biospecimens or the number analyzed for the primary IL-6 outcome.

Zero recorded events in the listed categories is not a comparative risk estimate. Without event details, uncertainty estimates, and fuller follow-up information, the registry counts do not support a broader conclusion about safety.

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

The registry record establishes that PATHFINDER II was a completed randomized, single-masked, parallel-group study with planned enrollment of 70. It describes a comparison between an EEG-guided MMGA strategy and standard-of-care control in cardiac surgical patients. Its primary question concerns changes in plasma IL-6 from baseline to postoperative day 1 and postoperative day 2.

The record does not report numerical results for the primary comparison or the listed secondary outcomes. It therefore does not show whether IL-6 changed differently between groups, how large any difference was, or how uncertain an estimate might be. It also does not support conclusions about the effects of the strategies on delirium, cognition, pain, opioid consumption, burst suppression, or vasopressor dose.

The zero serious adverse events and zero deaths reported in both groups are limited registry counts. They do not establish that every possible adverse event was absent, nor do they provide a formal comparison of safety. Further details about event definitions and follow-up are not reported in the registry record.

General interpretation: an outcome that was planned is not the same as an outcome with a posted result. Likewise, a completed study does not, by itself, reveal whether the tested strategy performed better, worse, or similarly to the comparator. Those judgments require estimates, uncertainty measures, and adequate information about the analysis and participants included. The registry record supports understanding the research question and some design features, but not a conclusion about comparative efficacy or safety.

13. Why This Trial Matters Statistically

This study raises a statistical question about a multicomponent perioperative strategy rather than a single isolated intervention. The MMGA arm combines EEG guidance with several anesthetic components and a postoperative analgesic approach, while the comparator is standard care. In general, a randomized comparison of bundles can assess the assigned strategies as wholes, but it cannot identify the separate contribution of each component without additional design or analysis.

The primary outcome is measured repeatedly: at baseline and at two postoperative time points. That structure makes the definition of the comparison important. An analysis of change at each time point, a joint analysis across time, and a single selected time-point analysis answer different questions. The registry describes separate changes from baseline but does not report a multiplicity plan or statistical model.

Missing or inadequate biospecimens also matter because the number analyzed differs from the number assigned and can vary by time point. Statistical interpretation depends not only on the planned enrollment but also on which participants have valid measurements and how missing data are handled. The registry record does not report the time-specific IL-6 analysis counts or further missing-data methods.

These design and reporting details illustrate why trial interpretation relies on outcome estimates, uncertainty, analysis populations, and prespecified methods—not only on a study’s aims or completion status. In this record, those results and methods are not reported, so the trial’s comparative findings cannot be evaluated.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report analyzed primary-outcome results, including group summaries, between-group estimates, confidence intervals, or p-values. It also does not provide numerical results for the listed secondary outcomes. This prevents assessment of effect direction, size, precision, and statistical evidence.

The primary outcome uses more than one postoperative time point. The record does not describe a multiplicity strategy, the planned statistical model, covariate adjustments, or a detailed analysis plan. The registry says that participants without valid biospecimens were excluded from the relevant time-point analysis, but does not give the number with valid samples at each time point or describe further missing-data handling.

The intervention descriptions are incomplete. The control description includes routine intraoperative practice and a postoperative regimen, while the MMGA description is truncated after beginning to list dexmedetomidine. The full intervention protocols and masking details are not reported in the registry record. The registry lists single masking without identifying who was masked.

The record does not report the trial’s sample-size justification, eligibility criteria, or detailed safety follow-up and event definitions. The reported serious adverse-event counts are limited to the listed participants at risk and do not include event terms. These limitations constrain interpretation of both the study’s methods and its results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies — NCT05279898.
• Registry record last updated 2025-11-26; status last verified 2025-11.
• Results first posted 2025-11-26.
• 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.

18. Record Summary

PATHFINDER II is a completed, randomized, single-masked, parallel-group study sponsored by Beth Israel Deaconess Medical Center. The registry lists planned enrollment of 70, phase NA, a start date of 2023-02-28, and primary completion on 2024-06-30. It compares an EEG-guided MMGA bundle with standard-of-care control in cardiac surgical patients.

The primary outcome is change in plasma IL-6 from baseline to postoperative day 1 and postoperative day 2, summarized as a mean with standard deviation. The record describes missing or inadequate biospecimens and time-specific exclusion of participants without valid samples. It lists eight outcome measures and zero analyses. Numerical efficacy results are not reported in the registry record.

The record reports zero serious adverse events and zero deaths in each group among the participants listed as at risk. Further analysis and safety details are not reported.