Effect of Remifentanil on Hemodynamic Stability During Placement of a Mayfield Head Fixation Device for Craniotomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Remifentanil on Hemodynamic Stability During Placement of a Mayfield Head Fixation Device for Craniotomy (NCT02430389), a randomized na study. The primary outcome is Mean Arterial Blood Pressure After Head Fixation.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group trial. The registry lists 20 participants enrolled and gives 10 participants in each arm for the posted outcomes. The trial is marked terminated. Its phase is listed as not applicable. The sponsor was Northwestern University.

The two arms received an intravenous bolus from a study syringe ninety seconds before head pinning. The remifentanil arm received 10 mL of remifentanil at 0.7 mcg/kg based on ideal body weight; the comparator arm received 10 mL normal saline. Both descriptions also specify an intravenous propofol bolus at 0.7 mg/kg. The record therefore describes a comparison of remifentanil with saline on top of the listed propofol administration.

The primary outcome was mean arterial blood pressure, measured in mm Hg, over the ten-minute window after head fixation. The secondary outcome was the number of participants requiring rescue therapy for hemodynamic perturbations in the ten-minute window after fixation. The registry describes the primary outcome as a mean with standard deviation. It does not provide additional details about how repeated blood-pressure measurements were combined into the reported mean.

The study start is listed as 2012-07 and primary completion as 2012-11. Further details about randomization implementation, masking procedures, allocation concealment, trial conduct, or reasons for termination are not reported in the registry record. The record also does not describe the original sample-size justification or its planned statistical analysis in sufficient detail to assess those design decisions.

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

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 Mean Arterial Blood Pressure After Head Fixation, measured over Ten minute window after head fixation.

Mean arterial blood pressure is a continuous measure of pressure in the arteries averaged over the cardiac cycle. For this trial, the registry reports the group mean and standard deviation for the ten-minute window after head fixation, with measurements expressed in mm Hg. The endpoint is intended to capture blood-pressure levels during a defined period following the placement of the head fixation device.

Comparing group means gives a concise description of the average outcome in each randomized arm. The standard deviation describes how spread out individual measurements were around each arm’s mean; it is not the uncertainty around the mean itself. A difference in group means therefore addresses whether average pressure levels differed, while the spread and uncertainty interval help show how precisely that difference is estimated.

The endpoint represents one aspect of hemodynamic stability, not every possible aspect of circulation or clinical status. A group average can also conceal variation among individuals, including brief changes within the measurement window. The registry record does not report the underlying repeated measurements, individual trajectories, or details of the measurement schedule. The posted endpoint should therefore be read as an average over the specified window, rather than as a complete account of each participant’s blood-pressure course.

7. Results Posted in the Registry

• Normal Saline: mean 83.00 versus 76.00 on control; difference 7.00 (95% CI -1.94 to 15.94), standardized effect d = 0.69; z-test p = 0.125.

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 Patients Requiring Rescue Therapy for Hemodynamic Perturbations

• 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:
  • Normal Saline: 80.0% (8/10) versus 50.0% (5/10) on control; risk difference 30.0 percentage points (95% CI -9.7 to 69.7), risk ratio 1.60 (0.80–3.20); unadjusted two-proportion z-test p = 0.160.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Normal Saline and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts a secondary endpoint concerning whether rescue therapy was required for hemodynamic perturbations during the ten-minute window after fixation. In broad terms, its observed pattern points in the same direction as the primary outcome: the remifentanil arm has fewer participants requiring rescue therapy, just as its mean arterial pressure is lower. This directional consistency is descriptive; it does not establish that the outcomes provide independent confirmation of one another.

The secondary result is imprecise, and its uncertainty interval includes no difference. It therefore adds limited evidence about the size or direction of an underlying difference. It should be read alongside, rather than as a replacement for, the primary endpoint. The registry’s own analysis for the secondary outcome is also reported separately from the unadjusted recalculation, and neither result removes the uncertainty in the observed counts.

In general, secondary outcomes can help describe other aspects of a trial, but their interpretation is affected by how many outcomes and analyses were considered. Testing multiple outcomes increases the chance that at least one result may appear notable due to sampling variation. An adjustment for multiplicity can address some of this issue, but whether adjustment was planned or performed is not reported in the registry record. The secondary finding should consequently carry less weight than a prespecified primary analysis, particularly when the analysis plan and multiplicity handling are unavailable.

The registry lists one secondary outcome. Its relationship to the primary measure is clinically related in subject matter, but the record does not establish that it is a formal validation measure or explain how the endpoints were prioritized. The overall pattern is therefore best described as directionally similar but statistically uncertain, without treating the secondary result as decisive evidence.

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

• Number of Patients Requiring Rescue Therapy for Hemodynamic Perturbations

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

The primary outcome is continuous, so a direct comparison can be expressed as the difference between the two group means. The recalculated difference uses the saline mean minus the remifentanil mean. With that orientation, a positive estimate indicates a higher observed average in the saline arm. The estimate is in the endpoint’s units, mm Hg, so it retains a direct measurement-scale interpretation.

A group mean is a summary, not a description of every participant. The standard deviations, 8.0 mm Hg for remifentanil and 12.0 mm Hg for saline, describe dispersion of measurements within their respective arms. Greater dispersion generally makes a group mean less precise when group sizes are limited. In general, the standard deviation and the standard error answer different questions: the former describes participant-level spread, while the latter describes uncertainty in an estimated quantity such as a mean or difference.

What does the interval add?

An uncertainty interval gives a range of values compatible with the estimate under the calculation’s assumptions. For the primary mean difference, the recalculated interval is -1.939 to 15.94 mm Hg. The interval includes zero, the value corresponding to no difference in group means under the stated subtraction. It also extends to values on either side of zero, so the posted summary statistics do not determine a precise direction. The confidence level for this interval is not reported in the registry record.

In general, an interval’s width reflects both the amount of information in the data and the variability in the outcome. Wider intervals indicate less precision. An interval is not a guarantee that the true value lies within its endpoints, nor does it assign equal credibility to every value in the range. Its interpretation depends on the statistical method and assumptions used to construct it.

How should a p-value be read?

The recalculated primary p-value is 0.125. In general, 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, the probability that the result occurred by chance, or a measure of the size or clinical importance of a difference. A p-value alone does not describe precision; the estimate and interval provide information about size and uncertainty.

The sponsor’s registry analysis is listed as a two-sided t-test, with p-value .0575 for the primary comparison. The summary-statistic recalculation is a separate unadjusted calculation. The registry record does not give further details such as the sponsor’s test statistic or an interval for that analysis. The method label alone does not establish every detail of implementation, so the reported analysis and the recalculation should be read as distinct results.

What changes for the binary secondary outcome?

The secondary endpoint counts participants requiring rescue therapy. A risk is the proportion of participants with the event in an arm. A risk difference subtracts one arm’s risk from the other; here the recalculation is oriented as saline minus remifentanil. Its estimate is 0.3, and its interval ranges from -0.097 to 0.697. The interval includes zero, so the summary statistics are compatible with no difference in event risk as well as differences in either direction. The recalculated p-value is 0.16.

In general, binary outcomes can be summarized with several measures, including a risk difference, risk ratio, or odds ratio. These measures answer different questions and can have different numerical behavior, especially with small groups or sparse events. The risk difference is expressed on the absolute probability scale, whereas the risk ratio compares probabilities proportionally and the odds ratio compares odds. A measure should be interpreted with its orientation and uncertainty interval in mind. These recalculated comparisons are unadjusted; they do not account for any other outcomes or analyses.

Why can estimates be unstable in small groups?

With relatively few participants, an individual observation can have substantial influence on an arm’s summary, and the estimate may vary considerably across samples. This is reflected in broad uncertainty. For a binary outcome, changing the status of an individual can also alter the estimated proportion noticeably. In general, small samples make it harder to distinguish a real difference from ordinary sampling variation. That is a reason to emphasize the estimate and its uncertainty rather than reduce interpretation to whether a p-value crosses a threshold.

The posted recalculations use unadjusted comparisons derived from the reported summary statistics. They do not reproduce any unavailable participant-level analysis. The registry record does not report a detailed statistical analysis plan, the handling of missing measurements, or the population used for every analysis. Those details matter because choices about eligible observations, missing data, covariate adjustment, and repeated measurements can affect estimates and uncertainty.

11. Confidence Intervals and Precision

The primary mean difference is estimated as 7.0 mm Hg, with a reported recalculated interval from -1.939 to 15.94 mm Hg. The interval is wide enough to include zero and values on both sides of zero. Thus, the estimate does not pin down whether the underlying average difference is positive or negative, or how large it might be. The confidence level for the interval is not reported in the registry record.

Precision depends on the variability in the outcome and the information available in each arm. The primary standard deviations are 8.0 mm Hg in the remifentanil arm and 12.0 mm Hg in the normal saline arm, with 10 participants reported per arm. Those summaries describe meaningful spread relative to the observed group means, and the interval indicates that the mean-difference estimate remains uncertain.

The secondary risk-difference estimate is 0.3, and its recalculated interval extends from -0.097 to 0.697. This interval also includes zero and encompasses differences in either direction. The event counts therefore do not give a precise estimate of the underlying difference in rescue-therapy risk. The interval is particularly important to read alongside the point estimate: a single estimate can appear definitive when separated from the range of uncertainty.

In general, confidence intervals describe uncertainty under a statistical procedure and its assumptions; they do not account automatically for every source of uncertainty, such as missing data, outcome measurement, or selective reporting. The registry record does not report the confidence level or full calculation details for these recalculated intervals. Their width, rather than a threshold-based label alone, is a useful indication that the posted results allow a broad range of possible effects.

12. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm, not total events. They are illustrations calculated from the observed effect and are not the trial’s original sample-size design. The registry record does not report the original design assumptions or sample-size justification.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. For the primary outcome, the illustration for 100% of the observed effect gives 34 participants per arm for 80% power and 45 participants per arm for 90% power. Planning for 75% of the observed effect gives 60 participants per arm for 80% power and 80 participants per arm for 90% power. Planning for 50% of the observed effect gives 134 participants per arm for 80% power and 179 participants per arm for 90% power.

In plain language, 80% power means that, under the planning assumptions and if the specified effect were the true effect, the design would have an 80% chance of detecting it using the stated testing approach. The 90% column describes a higher chance under those same assumptions, which generally requires a larger planned group. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants per arm.

These are planning illustrations, not observed power. They do not establish that the observed trial had a particular probability of finding a result, and they should not be read as a retrospective judgment of the trial’s success. The same principle applies to the secondary-outcome planning figures: they use the observed effect as a starting point and are not evidence that the original study was designed around those values.

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 = 7.000; pooled standard deviation σ = 10.198.
2. n = 2 × (1.96 + 0.842)² × 10.198² / 7.000² = 33.3, rounded up to 34 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 <- 7                      # observed difference in means
sigma <- 10.1980390271856                     # 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(2430389)
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 = 34 (80% power), 45 (90% power)
 75% of observed effect: n per arm = 60 (80% power), 80 (90% power)
 50% of observed effect: n per arm = 134 (80% power), 179 (90% power)
power.t.test: 34.3 
Simulated power at n = 34 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. Analyses Reported by the Sponsor

The registry’s own primary analysis is listed as a two-sided t-test and reports p-value .0575. Separately, the unadjusted recalculation from the posted group means and standard deviations gives a mean difference of 7.0 mm Hg, an interval from -1.939 to 15.94 mm Hg, and p-value 0.125. The registry also reports a two-sided t-test for the secondary outcome, with p-value .348; its unadjusted recalculation gives p-value 0.16.

These are different analysis results and should not be substituted for one another. The recalculations are simple, unadjusted calculations from the posted summary statistics; they are not a reconstruction of any unavailable participant-level analysis. The registry record does not include enough detail about the sponsor’s calculations, analysis population, handling of measurements, or other implementation choices to explain the numerical differences. No discrepancy flag is recorded, but that does not provide the missing analytical detail. The sponsor’s reported analysis should be identified as the registry’s own result, while the recalculation should be understood as a separate summary-statistic check.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and a secondary outcome, but details of a prespecified statistical analysis plan are not reported in the registry record. In particular, it is not reported in the registry record whether the trial planned an adjustment for testing multiple outcomes, how the primary and secondary analyses were prioritized, or whether any additional analyses were conducted. Without that context, p-values should not be interpreted as if the full set of planned tests were known.

Multiplicity matters because considering several outcomes or analyses creates more opportunities for a result to appear unusual under a null model. In general, adjustment procedures can control some forms of this increased false-positive risk, but they may also affect the interpretation of individual tests. It is not appropriate to assume that an adjustment was or was not used when the record does not say. The registry’s t-test labels and posted p-values do not by themselves describe a multiplicity strategy.

Information about missing outcome data, withdrawals, exclusions, and the number of participants included in each analysis is not reported in the registry record. Although 10 participants are listed per arm for the posted outcomes, the record does not fully explain whether every randomized participant contributed to each analysis or how missing measurements were handled. The analysis population, such as whether analyses followed assignment regardless of treatment received, is not reported in the registry record.

Interim analyses, stopping rules, and the statistical rationale for termination are also not reported in the registry record. The trial is marked terminated, but the reason and any implications for analysis cannot be inferred from that status alone. These omissions limit assessment of potential attrition, selective analysis, and the relationship between the planned and reported analyses. They do not show that a particular problem occurred; they mean that the available record does not resolve these questions.

16. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for 10 participants at risk in each arm and reports zero serious adverse events in each arm. No serious adverse-event terms are listed. These figures describe the serious-event information posted for the trial; they do not establish that there was no risk of serious events beyond the observation and reporting captured in the record.

The listed counts are based on small groups, so the absence of observed serious events should be interpreted cautiously. In general, an event not observed in a limited sample can still occur in a broader population. The registry record does not report additional detail about event definitions, surveillance procedures, or follow-up duration for adverse events. Death counts are not reported in the registry record.

These serious-event figures are separate from the primary blood-pressure outcome and the rescue-therapy endpoint. The record also lists other adverse events, but the serious-event counts alone should not be used to characterize all safety findings. The information supports only a description of the reported serious adverse-event counts, not a comparative safety conclusion.

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

The posted results describe a small randomized comparison of remifentanil and normal saline before Mayfield head pinning, with propofol specified in both arms. The observed primary means are lower in the remifentanil arm, and the rescue-therapy count also points in the same direction. Those patterns summarize what was observed in the registered groups; they do not establish a reliable difference in the wider population.

The recalculated primary interval includes zero and extends across values favoring either direction. The recalculated secondary interval likewise includes zero. These uncertainties mean the observed data are compatible with more than one account of the underlying differences. A point estimate alone should not be treated as a definitive treatment effect, and a p-value does not convey the likely clinical importance of a result.

These findings do not establish that remifentanil improves hemodynamic stability, nor do they establish that it has no effect. The endpoints capture average arterial pressure over a specified window and whether rescue therapy was required; they do not measure every dimension of perioperative care, patient experience, or longer-term outcome. The registry record does not report information that would support conclusions about outcomes outside the posted measures.

Interpretation is further limited by the enrollment size, termination status, and missing detail about the original design assumptions, analysis populations, missing data, multiplicity, and the reasons for termination. These limitations do not negate the posted observations, but they constrain how far those observations can be generalized or used to make causal claims beyond the randomized comparison as reported.

18. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison should be read through both its estimated effect and its uncertainty. The arm means and rescue-therapy counts point in a similar direction, yet the recalculated intervals include no difference and allow effects in either direction. That combination is more informative than treating a single p-value as a verdict.

It also demonstrates the distinction between a registry-reported analysis and an unadjusted recalculation from summary statistics. The sponsor’s analysis is reported with its own test and p-value, while the recalculations provide transparent comparisons based on posted group summaries. Without additional analytical detail, neither result should be made to stand in for the other.

The planning illustrations help show how design size relates to the effect a future study aims to detect. Their increasing participant requirements for smaller target effects make clear why modest or uncertain observed effects require careful planning. They are not evidence about the probability that this completed trial found a result.

Finally, the record’s omissions are statistically important. Missing details about analysis populations, missing data, multiplicity, and the rationale for termination limit the ability to assess robustness and selective reporting. Recognizing those limits is part of interpreting clinical trial evidence, not a claim that any unreported problem occurred.

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.

The enrollment was limited to 20 participants, with 10 listed in each arm for the posted outcomes. Such small groups leave estimates vulnerable to substantial sampling variation, consistent with the broad uncertainty around both primary and secondary comparisons. The results should not be treated as precise estimates of differences in a larger population.

The registry marks the trial as terminated, but the reason for termination and its relation to planned recruitment or analysis are not reported in the registry record. The original sample-size rationale, planned effect size, and planned statistical assumptions are also not reported in the registry record. The planning illustrations based on observed effects cannot fill that gap.

Although the study is described as randomized and triple-masked, details of sequence generation, concealment, who was masked, and how masking was maintained are not reported in the registry record. The record does not supply participant-level blood-pressure measurements or explain precisely how the ten-minute mean was assembled. It also does not describe missing-data handling, analysis-population definitions, or the use of any covariate adjustment.

The registry reports sponsor analyses as two-sided t-tests but does not provide the associated test statistics or confidence intervals. The simple recalculations cannot reproduce unavailable participant-level methods. Multiplicity procedures, interim analyses, and stopping rules are not reported in the registry record. These limitations reduce the ability to assess the robustness of the posted findings, but do not establish that any particular design or analysis flaw occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effect of Remifentanil on Hemodynamic Stability During Placement of a Mayfield Head Fixation Device for Craniotomy — NCT02430389.
• Registry record last updated 2015-06-30; status last verified 2015-06.
• Results first posted 2015-06-30.
• 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

NCT02430389 is a randomized, triple-masked, parallel-group trial sponsored by Northwestern University and marked terminated. It enrolled 20 participants undergoing craniotomy surgery. The intervention was remifentanil before head pinning, compared with normal saline; both arms were also described as receiving propofol.

The primary outcome was mean arterial blood pressure during the ten-minute window after head fixation. The posted means were 76.0 mm Hg for remifentanil and 83.0 mm Hg for normal saline. The recalculated unadjusted mean difference was 7.0 mm Hg, with an interval including zero. The registry also reports rescue therapy as a secondary outcome, with an observed pattern in the same direction and substantial uncertainty.

The registry includes sponsor-reported two-sided t-tests, but details about the original design assumptions, analysis populations, missing data, multiplicity, and reason for termination are not reported in the registry record. The posted estimates are therefore best read as limited and uncertain evidence about the measured outcomes.