Optimal VAsopressor titraTION Pilot Randomized Controlled Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimal VAsopressor titraTION Pilot Randomized Controlled Trial (NCT01800877), a randomized na study. The primary outcome is MAP While on Vasopressors.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group pilot trial with no masking listed in the registry record. Participants were assigned to a liberal or restrictive vasopressor titration approach. In the liberal group, the target mean arterial pressure range was 75 to 80 mmHg; in the restrictive group, it was 60 to 65 mmHg. Because masking was listed as none, the record describes the trial as unmasked.

The registered enrollment was 120. For the primary outcome, the posted group sizes were 58 for the liberal approach and 60 for the restrictive approach. The registry labels the trial status completed and lists the phase as NA. The intervention is identified as vasopressors.

The primary outcome was MAP While on Vasopressors, a continuous measure summarized as a mean and standard deviation. Its timeframe was while participants were on vasopressors from randomization until 28 days. The registry describes the outcome as a feasibility measure and sets a difference of at least 5 mmHg as the threshold for acceptable adherence.

The record lists one outcome measure and no posted secondary outcomes. It contains no analysis entries. The original sample-size justification, details of the randomization procedure, eligibility criteria, and any interim-analysis plan are not reported in the registry record. The record also does not describe how treatment assignment was implemented or how adherence to each target was monitored.

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 MAP While on Vasopressors, measured over While on vasopressors from randomization until 28 days.

The primary endpoint is mean arterial pressure (MAP) while participants were receiving vasopressors, measured from randomization until 28 days. MAP is expressed in mmHg. The outcome is summarized by the mean and standard deviation in each assigned group. In the posted results, the mean was 79.0 mmHg for the liberal approach and 70 mmHg for the restrictive approach.

This measure was chosen as a feasibility outcome: it reflects the blood-pressure levels attained under the two titration approaches. The registry states that acceptable adherence was defined using a difference of at least 5 mmHg between group means. That criterion concerns separation of the achieved MAP levels, rather than a clinical event or a patient-centered outcome.

The endpoint is specifically described as MAP while on vasopressors. It should not be read as a measure of MAP across all times, as an outcome measured after the vasopressor period, or as a direct measure of clinical benefit. The posted record does not report how individual repeated MAP measurements were combined to produce each participant’s endpoint value, nor does it give a separate endpoint result for other time periods.

7. Results Posted in the Registry

• Restrictive Approach: mean 70.00 versus 79.00 on control; difference -9.00 (95% CI -10.80 to -7.20), standardized effect d = -1.80; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: MAP in mmHg. The registry reports a mean and standard deviation for each group, then reports a mean difference comparing the restrictive approach with the liberal approach. This makes the direction of the comparison important: a negative difference means the restrictive group’s reported mean is lower than the liberal group’s mean. The reported difference is -9.0 mmHg.

What does a mean describe?

In general, a mean is a measure of the center of a set of observations. It is useful for summarizing a continuous outcome in each group, but it does not show every participant’s value or the shape of the observations. Here, the group means summarize MAP while participants were on vasopressors. The liberal group’s mean was 79.0 mmHg, and the restrictive group’s mean was 70 mmHg.

What does the standard deviation describe?

In general, the standard deviation describes how spread out individual observations are around their group mean. It is not the uncertainty of the mean itself and is not interchangeable with a confidence interval. The reported standard deviation was 5.0 in each group. The record does not give participant-level MAP observations, so the distribution of values, outliers, and any within-person pattern over time cannot be assessed from these summaries alone.

How should the mean difference be read?

The comparison is reported as restrictive approach minus liberal approach. Its estimate is -9.0 mmHg. This is a contrast between group means, rather than an individual participant’s change in MAP. The confidence interval endpoints are -10.8 and -7.195. In general, a confidence interval expresses uncertainty in an estimated contrast under a specified statistical procedure. Its interpretation depends on the procedure and confidence level; the confidence level and detailed procedure are not reported in the registry record.

What does the p-value say?

The posted p-value is unadjusted and is reported as p < 0.001. In general, a p-value describes how unusual the observed data, or data more extreme, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor does it quantify the size or importance of a difference. Since the registry gives no analysis entry, the precise test and its assumptions are not reported in the registry record.

Why does randomization matter?

In general, random assignment is intended to make assigned groups comparable in expectation, including with respect to characteristics not measured or reported. It provides a basis for comparing outcomes by assignment. The registry lists randomized allocation and a parallel model. It does not report the sequence-generation method, allocation concealment, or analysis population, so these procedural details cannot be assessed from the record.

What does lack of masking mean?

The record lists masking as none. In general, masking can reduce the influence of knowledge of treatment assignment on care, assessment, or reporting. A continuous measurement such as MAP may be objectively recorded, but the registry does not explain measurement procedures or how knowledge of the assigned target may have affected titration or outcome collection. Thus, the lack of masking is a design feature to keep in mind, not by itself proof that the reported measurement was biased.

Why can variability matter?

In general, variability affects the precision of a group mean and the comparison between groups. When outcomes vary more, distinguishing a group contrast from random variation can be harder without additional observations. The posted standard deviations are 5.0 in both arms. These are descriptive summaries; they do not reveal whether values changed over the vasopressor period or whether the analysis accounted for repeated readings or other data structure. The registry does not report those analytic details.

What does the pilot designation tell us?

The trial is identified as a pilot. In general, pilot trials can be used to assess feasibility and inform later research, and estimates from them can be imprecise. The registry explicitly frames the primary outcome as feasibility and states a difference threshold of at least 5 mmHg. It does not report the original sample-size justification or state that the observed estimate was intended as a definitive estimate of a broader treatment effect. The posted comparison should therefore be understood in the context of its feasibility aim and the limitations of the available record.

10. Confidence Intervals and Precision

The primary outcome comparison is reported as a mean difference of -9.0 mmHg, with a confidence interval from -10.8 to -7.195. The interval lies on the negative side of zero, consistent with the reported direction: the mean MAP while on vasopressors was lower in the restrictive approach group than in the liberal approach group. The interval conveys uncertainty about the size of the mean contrast under the interval procedure, rather than uncertainty about an individual participant’s MAP.

The endpoints indicate that the estimated contrast is not a single exact value. A confidence interval is generally narrower when the estimate is more precise and wider when it is less precise, but interpreting its coverage requires knowing the confidence level and calculation method. Those details are not reported in the registry record. The interval endpoints are reproduced as posted; no additional interval calculation is implied.

The group standard deviations were both 5.0, and the group sizes for this outcome were 58 and 60. These summaries provide context for the comparison, but they do not disclose the distribution of individual measurements or any repeated-measure structure. The reported unadjusted p < 0.001 supplies a separate measure of evidence under a null model; it is not a substitute for the interval and does not tell the reader how precise the estimate is by itself.

Because this is a pilot feasibility outcome, the interval should be read as uncertainty around the observed group contrast, not as a guarantee that a future study would reproduce the same estimate. The registry record does not report an adjusted interval, a confidence level, or additional outcome analyses.

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 calculated from the observed effect, rather than the trial’s own original design justification. The registry’s planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses the stated fraction of the observed effect as the effect to detect.

For an effect equal to 100% of the observed effect, the illustration gives 5 participants per arm for 80% power and 7 participants per arm for 90% power. For 75% of the observed effect, it gives 9 participants per arm for 80% power and 12 participants per arm for 90% power. For 50% of the observed effect, it gives 20 participants per arm for 80% power and 26 participants per arm for 90% power.

In general, power is the chance that a study will detect an effect of a specified size under the assumptions used for planning, if that effect is present. The 80% and 90% columns describe two different planning targets for that chance: the 90% target is more demanding. Smaller effects need more participants to detect them at a given power target, as the planning illustrations show. These figures are not observed power.

The planning calculations are based on the observed contrast, and their assumptions differ from unknown design assumptions for the trial itself. The registry record does not report the trial’s original sample-size justification. These figures should therefore be read only as conditional planning illustrations, not as evidence that the completed trial had a particular planned power or that its sample size was chosen using these assumptions.

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 = -9.000; pooled standard deviation σ = 5.000.
2. n = 2 × (1.96 + 0.842)² × 5.000² / -9.000² = 4.8, rounded up to 5 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 <- -9                      # observed difference in means
sigma <- 5                     # 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(1800877)
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 = 5 (80% power), 7 (90% power)
 75% of observed effect: n per arm = 9 (80% power), 12 (90% power)
 50% of observed effect: n per arm = 20 (80% power), 26 (90% power)
power.t.test: 6 
Simulated power at n = 5 per arm: 0.702 (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 record lists one outcome measure and no posted secondary outcomes. It contains no analysis entries. The primary outcome comparison has an unadjusted p-value, but no multiplicity adjustment or strategy for controlling error across multiple tests is reported in the registry record. With no secondary outcomes posted, the available record does not show a set of additional outcome tests to evaluate. It also does not establish whether any analyses beyond those recorded were conducted.

The record does not report the analysis population used for the primary comparison, such as whether participants were analyzed according to assignment or according to treatment received. It also does not describe exclusions after randomization, protocol deviations, or how missing outcome data were handled. The outcome group sizes are 58 and 60, while the registered enrollment is 120; the registry does not explain the relationship between these counts or whether any outcome observations were unavailable.

Missing-data methods can matter because a complete-case comparison may represent a different set of participants from the randomized population if some observations are absent. In general, methods for handling missingness rely on assumptions about why data are missing. No missing-data method or assumption is reported in the registry record, so it is not possible to assess whether missing observations affected the posted comparison.

The registry also does not report the statistical model, covariate adjustment, handling of repeated MAP readings, or any sensitivity analyses. These details would help a reader understand how the endpoint was reduced to a participant-level value and how the group comparison was estimated. Their absence is a limit on what can be concluded about the analysis, not evidence that any particular method was or was not used outside the registry record.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 60 participants at risk in each group. Zero participants in the liberal approach group and zero in the restrictive approach group were reported as affected by a serious adverse event. The record lists no serious-event terms. It also reports other adverse events for 60 participants at risk in each group: 45 were affected in the liberal approach group and 41 in the restrictive approach group.

These counts describe the registry’s reported event categories and participants at risk. They are not rates calculated here, and the other adverse-event category should not be treated as equivalent to serious adverse events. The record does not provide event definitions, the observation period for these safety results, event-level counts, or an analysis comparing groups. Death counts are not reported in the registry record.

The figures alone do not establish that one approach is safer than the other. They are descriptive counts, and the available registry information does not explain how events were collected, adjudicated, or related to treatment assignment.

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

The primary result describes mean MAP while participants were receiving vasopressors under two randomized target approaches. The liberal approach group had a reported mean of 79.0 mmHg, and the restrictive approach group had a mean of 70 mmHg. The reported mean difference, restrictive minus liberal, was -9.0 mmHg, with a confidence interval from -10.8 to -7.195 and an unadjusted p < 0.001. This is evidence of a difference in the measured endpoint between the assigned groups in this trial.

The result is directly relevant to the registry’s feasibility question because it compares achieved MAP under the two target ranges. The registry defines acceptable adherence using a difference of at least 5 mmHg. However, it does not give a separate adherence analysis or state a final feasibility judgment. The mean contrast should not be expanded into claims about how consistently individual participants met their assigned target.

The result does not establish differences in outcomes that are not reported as endpoints. The record lists no posted secondary outcomes, and the primary endpoint is a blood-pressure measure rather than a clinical event. The posted safety counts are descriptive and lack additional details needed for a comparative safety assessment. Neither the MAP result nor the adverse-event counts should be interpreted as general treatment advice.

The trial is described as a pilot, randomized, parallel, and unmasked. Those features provide context for the comparison, while missing analysis details limit assessment of the methods. The record does not report the original sample-size justification, analysis population, missing-data approach, statistical model, or confidence level. The most defensible reading is therefore focused: the registry reports different average MAP values between the two assigned approaches during vasopressor use, with an interval and unadjusted p-value, but does not establish broader clinical consequences.

16. Why This Trial Matters Statistically

This trial is statistically useful as an example of separating a feasibility measure from a clinical outcome. Its primary question concerns whether the assigned vasopressor targets produced a difference in mean MAP while participants were receiving vasopressors. The registry defines a difference of at least 5 mmHg as the threshold for acceptable adherence. That framing helps clarify what the primary endpoint was designed to assess: separation of achieved pressure levels between approaches.

The result also illustrates why a group mean contrast, its uncertainty, and a p-value are distinct pieces of information. The mean difference gives the estimated direction and size of the comparison; the confidence interval communicates uncertainty around that estimate under its procedure; and the unadjusted p-value describes compatibility with a null model. None alone gives a complete account of the trial, and none by itself establishes a clinical consequence.

Randomization and parallel assignment make the comparison interpretable as one between assigned approaches, while the lack of masking and the absence of detailed analysis information remain relevant when judging the strength of inference. The record does not report the analysis population, missing-data handling, or original sample-size justification. Those omissions matter because statistical interpretation depends not only on the reported estimate but also on how the data were collected and analyzed.

The trial’s pilot designation and feasibility focus are also important. Planning illustrations based on the observed contrast can help explain how assumed effect size and power targets relate to required participants, but they are not a substitute for the unknown original design rationale. Overall, the record offers a compact illustration of estimation, uncertainty, and the boundary between a measured physiological endpoint and claims about outcomes not reported.

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.

Several trial-specific limitations affect interpretation of the registry results. First, the study is identified as a pilot and the primary endpoint is a feasibility measure. The record does not report a separate feasibility conclusion or adherence results beyond the group MAP means. Therefore, the reported comparison does not describe how often individual participants stayed within their assigned target range.

Second, masking is listed as none. The registry does not describe the MAP measurement process, the frequency of measurements, or how measurements were combined while participants were on vasopressors. This limits assessment of possible influences of treatment awareness or measurement procedures on the endpoint.

Third, several analytic details are absent: the original sample-size rationale, statistical test or model, analysis population, missing-data handling, confidence level, and any sensitivity analyses are not reported in the registry record. The record lists 120 enrolled, while the primary-outcome group sizes are 58 and 60, without explaining the counts. No analysis entries or secondary outcomes are posted.

Finally, the safety information is limited to participant counts in serious and other adverse-event categories. Definitions, observation timing, event-level information, and deaths are not reported in the registry record. These limits mean the posted summary cannot support a detailed evaluation of event patterns or a broad assessment beyond the reported endpoint and counts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Optimal VAsopressor titraTION Pilot Randomized Controlled Trial — NCT01800877.
• Registry record last updated 2019-03-12; status last verified 2019-02.
• Results first posted 2019-03-12.
• 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 NCT01800877, the Optimal VAsopressor titraTION Pilot Randomized Controlled Trial. It is listed as a completed, randomized, parallel-group pilot trial with no masking, and registered enrollment of 120. The primary feasibility outcome was MAP while on vasopressors from randomization until 28 days.

The liberal approach targeted 75 to 80 mmHg and the restrictive approach targeted 60 to 65 mmHg. The reported means were 79.0 mmHg and 70 mmHg, respectively; the mean difference for restrictive versus liberal was -9.0 mmHg, with a confidence interval from -10.8 to -7.195 and an unadjusted p < 0.001.

The registry lists no posted secondary outcomes or analysis entries. It reports zero participants affected by serious adverse events in each group and other adverse events among 45 of 60 participants in the liberal group and 41 of 60 in the restrictive group. Death counts are not reported in the registry record.