Cerebral Oximetry and Neurological Outcomes in Aortic Arch Surgery Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cerebral Oximetry and Neurological Outcomes in Aortic Arch Surgery Patients (NCT01149148), a randomized phase 3 study. The primary outcome is Mini Mental State Examination (MMSE).

2. Clinical Question

3. Trial Design

This was a randomized, phase 3, parallel-group trial with triple masking. The registry lists enrollment of 25 and a completed status. The recorded start was 2009-11, and primary completion was 2010-05. The sponsor was the University of Michigan. The registry does not identify which trial roles were masked, describe the randomization procedure, or give further details about the conduct of the study.

The two groups were intervention INVOS cerebral oximetry monitoring and standard of care. The intervention description specified action when rSO2 dropped > 20% from baseline or declined below 50%. In the standard-care group, cerebral oximetry was blinded and did not guide intervention; surgery and anesthesia followed standard care without deviation. Both intervention entries in the registry name the INVOS Somanetics Cerebral Oximeter, while the arm descriptions distinguish the monitoring strategy and whether it guided care.

The posted primary outcome is mean MMSE at baseline, reported with standard deviations. The intervention group had a mean of 27.0 (standard deviation 1.651; 12 participants), and the standard-care group had a mean of 26.77 (standard deviation 2.048; 13 participants). These are baseline summaries, not follow-up results. Although the study hypothesis concerned neurological and cognitive outcomes after surgery, postoperative results for those outcomes are not reported in the registry record. The trial's original sample-size justification and design assumptions are also 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

Reasons for not completing this period:

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 Mini Mental State Examination (MMSE), measured over Baseline.

The primary endpoint is the Mini Mental State Examination (MMSE), a brief questionnaire used to screen for cognitive impairment, estimate its severity at a point in time, and follow cognitive change over time. The registry describes it as measuring general orientation and mental status. Scores range from 0 to 30, with scores of 23 and below described as indicative of problems. The posted endpoint is the mean score, a summary of the group's average performance on this continuous scale.

MMSE is used in cognitive research because it provides a structured measure that can be repeated to document change. For a treatment comparison focused on cognitive outcomes, measurements after treatment, or changes from baseline, would be relevant to whether scores differed over time. The registry's primary timeframe is Baseline. Thus the posted means characterize the groups before the intervention strategy could affect a later cognitive assessment. The registry does not report a postoperative MMSE result or a change-from-baseline result as the primary outcome. It also does not report a baseline-to-follow-up analysis for this measure. The results can describe baseline scores, but they do not answer whether the intervention changed cognitive outcomes after surgery.

7. Results Posted in the Registry

• Intervention INVOS Cerebral Oximetry Monitoring: mean 27.00 versus 26.77 on control; difference 0.23 (95% CI -1.22 to 1.68), standardized effect d = 0.12; z-test p = 0.755.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcome is continuous: each participant has an MMSE score, and the registry reports a group mean and standard deviation. A mean summarizes the score around which the group's observations balance. A standard deviation describes how spread out individual scores are around that mean. These two summaries provide useful context, but they do not show the full distribution of scores or whether individual participants improved or worsened.

What does the mean difference represent?

A mean difference compares the group averages on the same scale. The simple recalculation from the posted group summaries reports a mean difference of 0.231 for intervention versus standard care. This is an unadjusted comparison, meaning it uses the displayed summaries rather than a model that adjusts for other participant characteristics or baseline covariates. No adjusted estimate is reported in the registry record. The sign of a difference depends on which group is subtracted from which; the reported sponsor result is labeled net mean difference, but the registry does not provide enough detail to clarify its sign convention.

The clinical meaning of a mean difference depends on the outcome's scale, the timing of measurement, and the plausible range of important changes. The MMSE has a stated range from 0 to 30, but the registry does not report a threshold for a clinically important between-group difference. More fundamentally, these means are measured at baseline. They cannot be interpreted as a difference in postoperative change.

What does the t-test assess?

The sponsor's reported method is a two-sided t-test. In general, a t-test compares group means while accounting for the variability in the observations and the amount of information in each group. A two-sided test allows evidence of a difference in either direction. The reported p-value is 0.678. In general, a p-value measures how unusual the test result would be under a specified null model and its assumptions; it is not the probability that the null model is true. The registry does not report further details of the test implementation, including assumptions checks or whether any adjustments were made.

The simple recalculation also uses the posted means, standard deviations, and group sizes to estimate an unadjusted difference and its uncertainty. It yields p = 0.755. This recalculation is not a replacement for the sponsor's analysis. Differences between the recalculated and reported estimates can arise when the underlying analysis definitions or data differ, but the registry record does not specify a reason in this case. The registry does not flag a discrepancy.

Why does the confidence interval matter?

A confidence interval gives a range of values compatible with the data and the specified estimation method, while reflecting sampling uncertainty. It is not a guarantee that the true value lies in the interval, nor is it a range containing a stated proportion of individual participants. The recalculated 95% confidence interval is -1.222 to 1.684; the sponsor-reported interval is -1.36 to 2.02. Each includes zero. In general, an interval that includes zero does not establish the absence of an effect. It indicates that the estimate is uncertain enough that a zero difference remains compatible with the data under the method used.

Precision is affected by the amount of information in the analysis and by variability. More variability makes a group mean less precise when the amount of information is otherwise similar. A larger sample can narrow uncertainty, although the amount of narrowing depends on the design and analysis. These are general statistical principles; the registry does not report a trial-specific precision target or the original design calculation.

What is the role of the standard deviation?

The standard deviations, 1.651 in the intervention group and 2.048 in standard care, describe variation among baseline scores. They are not standard errors or confidence limits. A standard error describes uncertainty in an estimate, such as a mean, rather than spread among individual observations. The registry also reports standard errors in the comparison information, but the central interpretation rests on the estimated difference and its confidence interval. The registry does not provide individual participant data, so the distribution, outliers, and score frequencies cannot be assessed from the posted summaries.

What cannot be inferred from this analysis?

The posted analysis does not report a treatment effect on postoperative MMSE, an analysis of change from baseline, or a comparison of neurological dysfunction. It does not describe missing-data handling, an intention-to-treat population, or a per-protocol population. Nor does it describe model diagnostics, covariate adjustment, or a strategy for handling multiple outcomes. These details are not reported in the registry record. General principles about testing and estimation can help interpret the posted statistics, but they cannot fill gaps in the trial's actual analysis plan or outcome reporting.

10. Confidence Intervals and Precision

The simple recalculation gives a mean difference of 0.231 and a 95% confidence interval from -1.222 to 1.684. The sponsor's reported analysis gives a net mean difference of -0.333 and a 95% confidence interval from -1.36 to 2.02. The interval estimates differ, and the registry record does not provide enough methodological detail to reconcile them fully. The discrepancy flag is false, but both intervals include zero.

In general, a confidence interval conveys both the estimated direction and the uncertainty around that estimate. An interval including zero is compatible with no mean difference under the method used; because the intervals also extend to positive and negative values, the results remain compatible with differences in either direction. The interval should not be read as proving that the true difference is zero, nor as showing that clinically important changes are absent. The registry does not report a threshold for clinical importance that would allow that judgment.

The width of an interval reflects precision: narrower intervals indicate more precise estimates, while wider intervals leave more possible values compatible with the data. Here, the groups' baseline means are based on 12 and 13 participants, and the outcome has measurable variability. These features matter to the uncertainty, but the registry does not report a target precision or an original sample-size calculation. The confidence intervals concern baseline MMSE means. They do not quantify uncertainty about postoperative cognitive change, because that outcome is not posted as the primary result.

11. 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 are participants per arm, not total events. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. The registry does not report the trial's own original design assumptions or sample-size justification.

For planning at 100% of the observed effect, the listed requirements are 1,028 participants per arm for 80% power and 1,376 participants per arm for 90% power. At 75% of the observed effect, the figures are 1,827 participants per arm for 80% power and 2,445 participants per arm for 90% power. At 50% of the observed effect, they are 4,110 participants per arm for 80% power and 5,501 participants per arm for 90% power. The smaller-effect scenarios require more participants because a subtler difference is harder to distinguish from random variation under the same assumptions.

In general, 80% power means that, if the assumed effect and analysis conditions were true, the design would have an 80% chance of meeting the specified statistical significance criterion. The 90% column uses a higher chance of detecting that assumed effect, which entails a larger planned sample. These calculations are planning illustrations based on the observed baseline effect, not observed power. They do not establish what the original investigators planned, and they do not address whether the baseline effect is a clinically meaningful target for a postoperative outcome.

12. 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 = 0.231; pooled standard deviation σ = 1.869.
2. n = 2 × (1.96 + 0.842)² × 1.869² / 0.231² = 1,027.3, rounded up to 1,028 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 <- 0.231000000000002                      # observed difference in means
sigma <- 1.86868308663103                     # 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(1149148)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,028 (80% power), 1,376 (90% power)
 75% of observed effect: n per arm = 1,827 (80% power), 2,445 (90% power)
 50% of observed effect: n per arm = 4,110 (80% power), 5,501 (90% power)
power.t.test: 1028.2 
Simulated power at n = 1,028 per arm: 0.804 (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.

13. Analyses Reported by the Sponsor

The sponsor's reported analysis is a two-sided t-test with a net mean difference of -0.333, a 95% confidence interval from -1.36 to 2.02, and p = 0.678. The simple unadjusted recalculation from the posted group summaries gives a mean difference of 0.231, a 95% confidence interval from -1.222 to 1.684, and p = 0.755. The estimates differ in sign, and their intervals are not identical. The registry does not give sufficient detail about the net-difference convention, analysis inputs, or implementation to explain the difference.

The registry's discrepancy flag is false. The sponsor's analysis should be read as the analysis reported by the trial record, while the recalculation is a separate check using the posted summary statistics. Neither result is a postoperative treatment-effect estimate: both are associated with the baseline MMSE comparison. Both confidence intervals include zero, but that does not establish equivalence or demonstrate that no difference exists. The record does not report a subsequent MMSE analysis that could answer the stated question about neurocognitive outcomes after surgery.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and reports one analysis, but it does not post secondary results. The primary outcome described in the available result is baseline MMSE. The registry does not explain how the outcomes were prioritized for statistical testing or whether the study planned additional analyses beyond the one reported.

Multiplicity arises when researchers conduct several statistical tests or assess several outcomes. In general, repeated testing can increase the chance of obtaining a nominally significant result by chance if no adjustment or prespecified testing strategy is used. Whether that concern applies, and how it was handled, cannot be established from the registry record. A multiplicity adjustment, hierarchical testing plan, or other strategy is not reported in the registry record.

Missing-data handling is not reported in the registry record. The available summary does not say whether all randomized participants contributed to the MMSE analysis, whether measurements were unavailable, how any missing values were treated, or whether sensitivity analyses were performed. These details matter because analyses can be affected if outcome availability is related to treatment assignment or participant characteristics. No conclusions about the presence or impact of missing data can be drawn from the posted summaries.

The analysis population is also not reported in the registry record. The record does not state whether the analysis followed an intention-to-treat principle, included participants according to treatment received, or used another population definition. The randomization method, allocation concealment, masking roles, and any departures from assigned treatment are not described in enough detail to evaluate their implementation. Although the trial is labeled triple-masked, which roles were masked is not reported. These omissions limit assessment of how the analysis preserves the randomized comparison and how fully the posted result represents the planned study.

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

Serious events with the highest arm-level rate: death (8.3%).

The serious adverse event figures show 1 affected participant among 12 at risk in the intervention group and 0 among 13 at risk in standard care. The registry also lists Death as a top serious-event term at 8.3% for the intervention group. The death fields themselves are recorded as null, and no serious-event term is listed for standard care. This means the registry's event-term listing and its separate death fields do not give a fully detailed account of fatal outcomes; further clarification is not reported in the registry record.

These counts describe what was posted, not a comparative safety test. The registry does not provide event timing, clinical descriptions, relatedness to the device or procedure, or enough detail to interpret the listed term further. No other adverse-event counts are reported as affected in either group. Such small group summaries are descriptive and do not establish whether an event rate differs between strategies. The absence of a reported event in a group is not proof that risk is absent, and the record does not support conclusions about comparative safety.

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

The posted primary results describe baseline MMSE scores in the two randomized groups. The intervention group's mean was 27.0 and the standard-care group's mean was 26.77. The recalculated mean difference is 0.231, with a confidence interval spanning values below and above zero. The sponsor's reported interval also includes zero. These summaries indicate uncertainty about the baseline difference; they do not establish equivalence, prove a difference, or quantify a treatment effect.

The timing is decisive for interpretation. The stated hypothesis concerns optimizing cerebral oxygenation during surgery and subsequent neurological or cognitive outcomes. The primary result posted in the registry is at baseline, before the intervention could influence later cognitive scores. There is no reported postoperative MMSE comparison or change-from-baseline estimate among the posted primary results. The baseline scores therefore cannot show whether cerebral oximetry monitoring altered cognitive outcomes after surgery. They also do not report the incidence of transient or permanent neurological dysfunction.

A non-significant p-value is not proof that the strategies have the same outcome. General statistical interpretation treats a p-value as evidence assessed under a specified model, not as a direct measure of clinical importance or the probability that a treatment works. The confidence intervals indicate that the estimated baseline differences are imprecise enough to remain compatible with values on either side of zero. The registry does not identify a clinically important MMSE difference that could be used to judge whether the range of estimates matters clinically.

The small enrollment and lack of a reported original design rationale are relevant context, but they do not justify claims about observed power. The separate planning illustrations are based on the observed baseline effect and specific assumptions; they are not evidence about the trial's original plan. A fuller answer to the clinical question would require reported post-surgical outcomes, their timing, and a clearly described analysis. Those details are not reported in the registry record, so conclusions about postoperative cognitive benefit or harm are not supported by the available primary result.

17. Why This Trial Matters Statistically

This trial illustrates why outcome timing is as important as the choice of statistical test. A baseline score can describe the groups before treatment, but it cannot show whether an intervention changed the outcome later. The investigators' stated hypothesis focuses on neurological dysfunction and neurocognitive impairment after cerebral oxygenation monitoring during surgery. The posted primary measure is baseline MMSE. Recognizing that mismatch prevents a baseline comparison from being mistaken for evidence about postoperative outcomes.

It also highlights the value of reporting estimates with confidence intervals rather than relying on a p-value alone. The mean difference and its interval make the direction and uncertainty visible, while the p-value is only one summary under a testing framework. Here, the intervals cross zero, and neither the sponsor analysis nor the simple recalculation demonstrates that a baseline difference is absent. Precision and clinical importance are separate questions; the registry does not specify a clinically important MMSE difference.

Finally, the record demonstrates the limits of interpreting summary statistics without analysis details. The sponsor estimate and the simple recalculation differ in sign, but the record does not explain the convention or inputs that would reconcile them. Details on missing data, analysis populations, multiplicity, and the original sample-size rationale are not reported. These are not cosmetic omissions: they affect how confidently readers can connect a posted result to the study's intended question. Transparent outcome timing and analysis reporting are essential for a clinically relevant statistical interpretation.

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 principal trial-specific limitation is that the posted primary outcome is MMSE at baseline, while the study hypothesis concerns neurological and cognitive outcomes following surgery. The record does not provide a postoperative primary result or a change-from-baseline analysis. Consequently, the posted result cannot answer whether the monitoring strategy affected later cognition or neurological dysfunction.

Enrollment was 25, and the group summaries are based on 12 participants in the intervention arm and 13 in standard care. With limited information and variability in the scores, the estimated difference is uncertain. The registry does not report an original sample-size calculation, a target difference, or the rationale for enrollment. The planning illustrations are not a substitute for those design details.

The sponsor's reported mean difference and the simple recalculation from posted summaries have different signs. The registry does not provide enough detail about the net-difference convention, participant-level data, or analysis implementation to resolve the difference. The registry does not flag a discrepancy, but readers cannot independently reconstruct the sponsor analysis from the posted summaries alone.

Important design and analysis details are not reported in the registry record, including eligibility criteria, randomization procedures, which roles were masked, missing-data handling, analysis population, multiplicity strategy, and whether analyses were adjusted. The posted safety information is also sparse: the serious-event term Death is listed at 8.3%, while death fields are null. This limits interpretation of the safety record. These limitations should be kept distinct from findings; the registry record does not establish that unreported events, procedures, or analyses did or did not occur.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cerebral Oximetry and Neurological Outcomes in Aortic Arch Surgery Patients — NCT01149148.
• Registry record last updated 2015-04-28; status last verified 2012-08.
• Results first posted 2012-08-16.
• 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

NCT01149148 is a completed phase 3 randomized parallel-group trial sponsored by the University of Michigan. It compared intervention-triggered INVOS cerebral oximetry monitoring with blinded monitoring and standard care during aortic arch surgery. The recorded enrollment was 25. The intervention trigger was an rSO2 drop > 20% from baseline or a decline below 50%.

The posted primary outcome is baseline MMSE. Mean scores were 27.0 in the intervention group and 26.77 in standard care. The sponsor reported a two-sided t-test with p = 0.678; a simple recalculation from posted summaries gives a mean difference of 0.231 and p = 0.755. The result is a baseline comparison, not a reported postoperative treatment effect. Postoperative cognitive and neurological outcome results, original sample-size assumptions, and several analysis details are not reported in the registry record.