Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients (NCT00795366), a randomized na study. The primary outcome is Time ICP >20.

2. Clinical Question

This is a comparison of an outcome measured over a defined monitoring period, rather than a direct measure of all aspects of brain injury or recovery. The endpoint records time spent above an intracranial-pressure threshold. It does not itself establish whether any observed difference translated into a difference in patient-centered outcomes.

The record describes a randomized, parallel-group trial without masking. Random allocation is relevant because it is intended to make treatment groups comparable on average, but the registry record does not report the randomization method or allocation concealment. Nor does it report whether other aspects of care were standardized. Those details matter when interpreting how far the outcome comparison can be attributed to the assigned treatment rather than differences in care or measurement.

3. Trial Design

The registry identifies this as a randomized, parallel-group trial with no masking. Its title concerns vasopressin versus catecholamines for cerebral perfusion pressure control in brain-injured trauma patients. The listed condition is traumatic brain injury, and the intervention arms are arginine vasopressin and standard catecholamine treatment. The registry lists University of Miami as sponsor and describes the study as completed.

Enrollment is listed as 96. The outcome records identify 42 participants in the AVP arm and 54 in the standard catecholamine arm. These are the group sizes associated with the posted primary outcome summaries. The registry does not report why the arm sizes differ or whether all randomized participants contributed to the outcome analysis.

The start is recorded as 2008-09 and primary completion as 2014-09. The phase is listed as NA. The registry record does not report the specific randomization procedure, allocation concealment, treatment duration, criteria for starting or changing treatment, or a detailed schedule of outcome measurement. It also does not report the trial's original sample-size assumptions or a statistical analysis plan.

Because the study was unmasked, participants and care teams were not blinded according to the registry entry. Whether outcome assessors were masked is not reported in the registry record. For an outcome based on monitored pressure values, measurement may be more objective than a subjective rating, but the way readings were collected, summarized, and checked can still matter. The registry does not provide enough detail to assess those procedures.

The primary analysis population is identified as intent-to-treat. That label indicates the intended population for the outcome, but the registry does not report how missing measurements, protocol deviations, or treatment changes were handled. There are no posted secondary outcome measures in the record described for this analysis, and no analysis records are listed.

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

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat

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 Time ICP >20, measured over The number of hours during the first 5 days of intracranial pressure monitoring.

The primary endpoint is the number of hours during the first 5 days of intracranial pressure monitoring that a participant remained with intracranial pressure above 20 mmHg. It is reported as a continuous measure in hours, with a mean and standard deviation for each treatment arm. The endpoint therefore captures the duration of elevated pressure over a defined observation period, rather than only whether a participant ever crossed the threshold.

Intracranial pressure is relevant to the trial's clinical question because the registry background describes management of cerebral perfusion pressure as an approach to limiting ischemic episodes after traumatic brain injury. In general, a measure of time spent above a clinically specified pressure threshold can describe the persistence of elevated pressure during monitoring. It may convey information that a single reading would not: a brief elevation and a prolonged elevation contribute differently to total hours.

The registry defines the threshold as greater than 20 mmHg and the observation window as the first 5 days of monitoring. It does not report the rationale for selecting that threshold or window, nor does it explain how periods of missing monitoring were treated. The endpoint is not itself a measure of cerebral ischemia, functional recovery, disability, or survival. Those outcomes should not be inferred from this pressure-duration measure.

7. Results Posted in the Registry

• AVP, Arginine Vasopressin: mean 1.70 versus 0.90 on control; difference 0.80 (95% CI -0.08 to 1.68), standardized effect d = 0.35; z-test p = 0.075.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it records hours with intracranial pressure above a threshold. The registry reports the mean and standard deviation in each randomized group, then gives a mean difference and confidence interval. These summaries answer related but distinct questions. The means describe the central value in each group, the standard deviations describe spread among observations, and the difference estimates the contrast between group means.

What does the mean difference represent?

The reported contrast is AVP minus standard catecholamine. The means are 1.7 hours for AVP and 0.9 hours for standard catecholamine, and the reported difference is 0.8 hours. A positive value therefore means that the estimated mean is higher in the AVP group for this endpoint. The sign describes the direction of the numerical contrast; it does not by itself indicate whether the contrast is important or reliable.

In general, a mean difference is useful when an outcome is measured on the same scale in both groups. It remains interpretable in the outcome's units, which are hours. Its limitations include sensitivity to unusually high or low observations and its inability to describe all features of the distributions. The registry does not report medians, quantiles, or participant-level data, so those features cannot be assessed from this record.

What do the standard deviations add?

The standard deviation describes how dispersed observations are around a group mean. The reported standard deviations are 1.8 hours for AVP and 2.6 hours for standard catecholamine. In general, greater dispersion means that individual outcomes vary more widely around the average. That variability affects the precision of a group comparison: when variability is large relative to the difference being estimated, the data usually give less precise information about the mean contrast.

A standard deviation is not a confidence interval and does not show the range containing every participant's outcome. It also does not establish whether distributions are symmetric or contain extreme values. No distribution plot or individual-level outcome data are described in the registry record, so the shape of the endpoint distribution cannot be evaluated from the reported summaries alone.

How should the confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimated effect under a statistical model and repeated-sampling framework. The interval for this mean difference includes zero, extending from a value slightly below zero to 1.682 hours. Zero corresponds to no mean difference between groups. An interval spanning zero indicates that the result is not precise enough to rule out that possibility at the interval's associated confidence level. The confidence level itself is not stated in the registry record, so it should not be assumed from the posted interval.

The interval also expresses a range of effect sizes compatible with the data and analysis assumptions. It is not a range of individual participant outcomes, and it does not assign a probability to the true effect being at a particular point. Its interpretation depends on the method used to calculate it. The registry does not report the interval construction method.

What does the p-value say?

The unadjusted p-value is 0.075. In general, a p-value summarizes how incompatible the observed data, or data more extreme, 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 is not a measure of the size or clinical importance of an effect.

The word unadjusted indicates that this reported comparison is not adjusted for multiplicity. The registry does not report whether any adjustments were planned or whether this result was selected from a broader set of analyses. The original analysis plan and detailed model specification are not reported in the registry record. Thus, the p-value should be read alongside the effect estimate and confidence interval, not as a stand-alone verdict.

What assumptions matter for a continuous outcome?

In general, inference based on group means can depend on how well the chosen statistical method handles the outcome distribution, unequal variability, and the way observations were collected. The record reports group standard deviations but does not describe diagnostic checks or a model for repeated monitoring readings. It is not possible to determine from the registry entry whether the primary analysis used a method that accounted for any such features.

The outcome is defined as cumulative hours above a threshold during the first 5 days of monitoring. General concerns for this kind of measure include incomplete monitoring and differences in the amount of observed time. The record does not say how these issues were addressed. These are analysis uncertainties, not evidence that any particular issue occurred.

10. Confidence Intervals and Precision

The estimated mean difference is 0.8 hours, with AVP minus standard catecholamine as the direction of comparison. Its confidence interval extends from a value slightly below zero to 1.682 hours. Since the interval includes zero, the estimate does not precisely distinguish a positive difference from no mean difference, and the lower end also allows a small difference in the opposite direction.

In general, a confidence interval is more informative than an estimate alone because it communicates the range of values reasonably compatible with the data under the analysis method. It is not a prediction interval for individual participants, nor does it mean that all values inside the interval are equally likely. The confidence level and calculation method are not reported in the registry record, which limits fuller interpretation of the interval's coverage properties.

The reported standard deviations, 1.8 hours in the AVP group and 2.6 hours in the standard catecholamine group, indicate variability in the measured outcome. The interval's width reflects uncertainty in the estimated contrast, but the registry does not report enough methodological detail to identify how much uncertainty arose from sampling variability, missing observations, or modeling choices.

The unadjusted p-value is 0.075. It is consistent with the interval's inclusion of zero, but p-values and confidence intervals convey different information: the interval gives an effect-size range, while the p-value summarizes compatibility with a null model under stated assumptions. The registry record does not identify the confidence level or the trial's prespecified inferential threshold. As a result, the numerical estimate should be interpreted with uncertainty rather than treated as a definitive distinction between treatments.

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 figures are participants per arm, not total events. They are illustrations based on the observed mean difference and are not the trial's original sample-size design. The stated 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 the stated fraction of the observed effect.

For planning based on 100% of the observed effect, the estimate is 129 participants per arm for 80% power and 172 participants per arm for 90% power. For planning based on 75% of the observed effect, the corresponding figures are 228 and 305 participants per arm. For planning based on 50% of the observed effect, they are 513 and 687 participants per arm.

In general, power is the probability that a study will detect an effect of a specified size under the planning assumptions, if that effect is the true one. The 80% power column means a planned study has an 80% chance of detecting the selected effect under those assumptions; the 90% column uses a higher target chance. Smaller effects need more participants to detect because they are harder to distinguish from random variation.

These are planning illustrations, not observed power. They rely on the observed effect as a reference and do not establish what sample size the trial originally intended to enroll. The trial's own design assumptions and sample-size justification are not reported in the registry record.

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 = 0.800; pooled standard deviation σ = 2.286.
2. n = 2 × (1.96 + 0.842)² × 2.286² / 0.800² = 128.1, rounded up to 129 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 <- 0.8                      # observed difference in means
sigma <- 2.28575607864528                     # 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(795366)
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 = 129 (80% power), 172 (90% power)
 75% of observed effect: n per arm = 228 (80% power), 305 (90% power)
 50% of observed effect: n per arm = 513 (80% power), 687 (90% power)
power.t.test: 129.1 
Simulated power at n = 129 per arm: 0.799 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no secondary outcome measures. It lists no analysis records. The posted comparison is unadjusted, and the registry record does not report whether the investigators planned additional analyses, interim looks, subgroup comparisons, or multiplicity adjustments. Without a statistical analysis plan, it is not possible to determine how the primary comparison fit into the complete set of planned analyses.

In general, multiplicity arises when many outcomes, time points, treatment contrasts, or subgroups are examined. Looking at multiple results can increase the chance that at least one appears noteworthy by chance. Adjustment methods can address some forms of multiplicity, but whether an adjustment is appropriate depends on the design and prespecified analysis strategy. No such strategy is reported in the registry record, so no correction should be inferred.

The primary outcome population is identified as intent-to-treat. In general, an intent-to-treat analysis aims to compare participants according to randomized assignment, regardless of treatment received after assignment. The registry does not explain whether every randomized participant was included in the posted outcome summaries or how deviations from assigned treatment were handled. The arm-specific outcome counts are reported, but the record does not describe participant flow or reasons for any unavailable measurements.

Missing data handling is not reported in the registry record. For an outcome based on hours of monitoring, incomplete observation could affect the measured duration, but the record does not say whether missing periods occurred or how they were treated. No imputation, sensitivity analysis, or missingness model is described. These are reporting gaps, not proof that data were missing or that the analysis was biased.

The record also does not report prespecified covariate adjustment, the handling of repeated readings, or checks of model assumptions. The unadjusted summary comparison can be described as posted, while its relationship to any fuller sponsor analysis cannot be assessed from the registry entry.

14. 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 (14.3%).

The registry lists serious adverse events affecting 6 participants in the AVP group and 6 in the standard catecholamine group. It lists 0 other adverse events affecting participants in either group. These are event summaries in the posted safety record; they do not provide enough detail to assess event timing, duration, severity beyond the serious classification, or relationship to treatment.

Among the top serious terms, the record lists Death at 14.3%. This is presented as a term-level percentage. The registry does not report a group-specific death count in the arm records, so the percentage should not be assigned to one treatment arm or interpreted as a direct comparison between groups. Death counts by arm are not reported in the registry record.

In general, serious adverse event summaries describe events meeting a serious classification, while other adverse event summaries may cover a separate category. They are not interchangeable with a complete assessment of safety. The registry does not report the definitions used, exposure time, event-level narratives, or statistical comparisons. Equal listed counts of serious adverse events do not establish that the types or consequences of events were the same.

These figures are descriptive. They do not establish that either treatment caused or prevented any listed event, and they do not support a broad comparative safety conclusion without fuller definitions, follow-up, and group-specific event detail.

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

The posted primary result is a mean difference of 0.8 hours in time with intracranial pressure above 20 mmHg, with the AVP group having the higher reported mean. The confidence interval includes zero, and the unadjusted p-value is 0.075. Together, these results describe an uncertain estimate rather than a precise separation between the groups for this endpoint.

This does not establish that the groups were equivalent. A result that does not clearly distinguish a difference from zero is not the same as evidence that any difference is absent or negligible. Demonstrating equivalence or non-inferiority would require a prespecified margin and a suitable analysis, neither of which is reported in the registry record.

The result also does not determine whether the observed difference is clinically important. The registry does not report a threshold for a meaningful change in hours, nor does this endpoint directly measure long-term neurological function, disability, or survival. No secondary outcomes are posted in the record, so effects on those outcomes cannot be inferred from the pressure-duration summary.

The trial's randomized design is useful for comparing assigned treatments, but the unmasked design and missing methodological detail should be kept in view. The registry does not report allocation concealment, assessor masking, missing-data procedures, or the detailed analysis plan. These omissions limit assessment of potential sources of bias and of how robust the result is to alternative analytic choices.

The safety listing is likewise limited. Serious adverse events affected 6 participants in each arm, and the top serious term list includes Death at 14.3%, without group-specific death counts. Those entries do not by themselves establish a comparative safety profile.

Overall, the registry records an imprecise primary-outcome comparison in a completed randomized trial. It does not justify a broader conclusion about treatment benefit, lack of benefit, or safety beyond the reported measures and uncertainty.

16. Why This Trial Matters Statistically

This trial illustrates why an estimated effect, its uncertainty, and the outcome's meaning need to be considered together. The mean difference of 0.8 hours gives a direct comparison on the endpoint's natural scale, while the confidence interval shows that the estimate remains compatible with values on both sides of zero. Reporting only the difference or only the p-value would leave out important information.

The group standard deviations are 1.8 and 2.6 hours, compared with group means of 1.7 and 0.9 hours. In general, variability matters because a study can estimate a group average imprecisely when participant outcomes vary widely. The reported interval makes that uncertainty visible; it discourages treating a single point estimate as if it were known exactly.

The trial also shows the importance of distinguishing a registry's design description from a complete analysis account. Randomized allocation and an intent-to-treat label are useful information, but details about allocation procedures, missing outcomes, masking of assessors, and the analysis plan are not reported. Statistical interpretation depends both on numerical results and on how those results were generated.

Finally, planning calculations based on an observed effect can be useful for illustrating how target power and effect size influence required enrollment. They are not evidence about the trial's original planning or about the probability that the completed trial detected an effect. Reading such illustrations as design details would conflate retrospective planning with the actual study protocol.

17. 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 gives limited detail about trial conduct and analysis. It identifies randomization and no masking, but does not describe the randomization method, allocation concealment, or whether outcome assessors were masked. The effects of these unreported procedures cannot be assessed from the registry entry.

The primary outcome is defined as hours above an intracranial-pressure threshold during the first 5 days of monitoring, but the record does not explain how monitoring gaps, repeated readings, or partial observation periods were handled. The distribution of the outcome is not reported beyond means and standard deviations. The reported summaries therefore cannot show whether observations were skewed or whether a small number of values influenced the means.

The outcome population is labeled intent-to-treat, but participant flow, treatment changes, protocol deviations, and missing-data procedures are not described. Although group sizes are reported for the primary outcome summaries, the registry does not explain the relationship between those numbers and the analysis of every randomized participant.

The statistical plan, original sample-size justification, significance threshold, interim analyses, and multiplicity strategy are not reported in the registry record. No secondary outcome measures or analysis records are listed. Consequently, it is not possible to assess the primary result in relation to a complete prespecified outcome and analysis hierarchy.

Safety reporting is also limited: event definitions, timing, exposure, and group-specific death counts are not reported. These limitations do not demonstrate that a particular problem occurred; they identify questions the registry record does not resolve.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients — NCT00795366.
• Registry record last updated 2014-12-12; status last verified 2014-12.
• Results first posted 2014-12-12.
• 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.

21. Record Summary

The registry describes a completed randomized, parallel-group trial without masking, sponsored by University of Miami. Enrollment is listed as 96. The comparison was arginine vasopressin versus standard catecholamine treatment in participants with traumatic brain injury.

The primary outcome was the number of hours with intracranial pressure above 20 mmHg during the first 5 days of monitoring, in an intent-to-treat population. The means were 1.7 hours for AVP and 0.9 hours for standard catecholamine, with a reported mean difference of 0.8 hours and an unadjusted p-value of 0.075. The confidence interval includes zero.

The registry lists 6 participants with serious adverse events in each arm and 0 with other adverse events in either arm. Death is listed at 14.3% among the top serious terms, without group-specific death counts. The record does not report secondary outcomes or analysis records.