Phenylephrine Versus Ephedrine in Pre-eclampsia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phenylephrine Versus Ephedrine in Pre-eclampsia (NCT02025426), a randomized phase 4 study. The primary outcome is Cerebral Tissue Oxygen Saturation.

2. Clinical Question

The primary endpoint is listed as cerebral tissue oxygen saturation, with a unit of mmHg. The measurement period begins at spinal placement and continues until 10 min after delivery. The registry describes the primary outcome as a mean of a continuous measure and reports a mean and standard deviation for each arm. The inferential comparison it reports is a Kruskal-Wallis test, with p = 0.547.

This is a comparison of two assigned vasopressor groups in a particular clinical setting, not a general comparison of these drugs across all uses. The registry summary states that phenylephrine administration is associated with reductions in cardiac output and cerebral tissue oxygen saturation compared with ephedrine. However, the posted primary endpoint means are numerically higher in the phenylephrine group, and the reported test does not indicate a statistically clear difference. Those features make it important to distinguish the registry's summary statement from the posted primary endpoint figures, and to interpret both in light of the small enrollment and the reported analysis.

3. Trial Design

The registry describes a phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Duke University. Its title is Phenylephrine Versus Ephedrine in Pre-eclampsia, and its official title describes the impact of vasopressor administration on maternal and neonatal outcomes in women with pre-eclampsia. The listed condition is pre-eclampsia. The registry reports enrollment of 13 and a terminated status.

The two interventions were phenylephrine and ephedrine. In both arms, the stated purpose of administration was maintaining blood pressure within 10 % of baseline. The registry does not report the allocation ratio, the randomization procedure, the identity of the masked parties, or the reason for termination. Those details are not reported in the registry record.

The listed start date is 2012-09, and the primary completion date is 2016-07-08. The primary measurement period was intraoperative, from spinal placement until 10 min after delivery. These dates describe the registry entries; they do not establish when each participant was enrolled or when each measurement was collected.

The primary endpoint was cerebral tissue oxygen saturation. Cardiac output is listed as a secondary outcome, and the registry records 8 outcome measures and 7 analyses. It does not report the complete set of outcome definitions, analysis populations, or results in the registry record for this explanation. The enrollment figure describes the trial record; the arm-level primary outcome summaries report 9 participants for phenylephrine and 4 for ephedrine. The registry does not explain whether any difference between enrollment and outcome-specific group counts reflects exclusions, missing measurements, or another reason.

Random allocation is intended, in general, to support a fair comparison by reducing systematic differences between assigned groups. Masking can, in general, reduce the influence of expectations on care or outcome assessment. The practical details of those protections in this trial are not reported in the registry record, so their implementation cannot be assessed from the available information.

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 Cerebral Tissue Oxygen Saturation, measured over Intraoperative from spinal placement till 10 min after delivery.

Cerebral tissue oxygen saturation is the trial's primary endpoint. The registry labels it a continuous measure, reports its mean and standard deviation for each arm, and gives the unit as mmHg. Its stated timeframe is intraoperative, from spinal placement until 10 min after delivery. The registry does not give a more detailed measurement definition, device description, or explanation of how readings across that period were reduced to the reported mean.

In general, a continuous endpoint can retain more gradation than an outcome recorded only as an event or category. A mean gives a measure of the group's central level, while a standard deviation describes the spread of individual measurements around that mean. A change in cerebral tissue oxygen saturation may be of interest as a measure of cerebral oxygenation during the specified period. The registry record does not report a threshold for clinical importance or explain how this measure relates to maternal or neonatal outcomes.

The posted means are 30.08 for phenylephrine and 19.1 for ephedrine. Their standard deviations are 29.32 and 7.23, respectively. The reported test is Kruskal-Wallis, rather than a test identified as a comparison of means. Thus, the mean summaries describe the observed groups, while the p-value comes from the stated test; they should not be treated as though the p-value were necessarily calculated from those means and standard deviations under a normal-theory model.

The unit and endpoint definition are reproduced as recorded. Further measurement details, the handling of repeated readings, and any prespecified approach to selecting or aggregating readings are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is treated in the registry as a continuous measure summarized by a mean and standard deviation. The inferential method reported for the two groups is the Kruskal-Wallis test. The registry does not provide a fuller statistical analysis plan, so the reason for selecting this test, any model details, or any adjustments cannot be established from the record.

What does a mean describe?

In general, a mean is the arithmetic center of a set of measurements. It is useful for describing a group's average level, but it does not show how observations are distributed or whether a few unusually high or low values influence the average. In this trial, the reported means are 30.08 for phenylephrine and 19.1 for ephedrine. The record gives standard deviations of 29.32 and 7.23, respectively. Those values are descriptive summaries, not estimates of uncertainty around the difference between groups.

What does a standard deviation describe?

In general, a standard deviation describes the dispersion of observations around their group mean. It is not a confidence interval and does not directly state how precisely the group mean or the between-group effect has been estimated. The different reported spreads suggest that the measurements may vary differently between arms, but the record does not provide individual observations or distribution plots to assess their shape. In particular, the available information does not establish whether observations are symmetric, skewed, or influenced by outliers.

What does the Kruskal-Wallis test assess?

In general, the Kruskal-Wallis test is a rank-based method for comparing groups. It uses the ordering of observations rather than relying on a direct comparison of group means under a normal-theory model. The registry reports this method and p = 0.547 for the primary comparison. The record does not describe the exact analysis implementation or provide additional test statistics. Because the test is rank-based, the p-value should not be interpreted as a test specifically of the numerical difference between the two reported means. A rank-based test may be useful when the assumptions of a conventional mean-based analysis are not suitable, but the reason it was chosen for this trial is not reported in the registry record.

How should the p-value be read?

General statistical explanation: a p-value describes the compatibility of data with a null hypothesis under a particular statistical model. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result will repeat. The reported p = 0.547 is not a confidence interval and does not show the range of effect sizes compatible with the data. The registry does not report a confidence interval for the primary between-group comparison, so readers cannot use an interval to assess the range of plausible effects from this record.

A p-value also does not by itself establish clinical importance. A small p-value can accompany an effect that is not important in practice, and a larger p-value can occur when an estimate is imprecise. The trial's arm counts are small, and the registry reports no interval estimate for the comparison. Consequently, the test result should be considered alongside the group summaries, the measurement context, and the uncertainty left unquantified in the posted results.

Why does variability matter?

General statistical explanation: when measurements are highly variable, it can be harder to distinguish a group difference from ordinary fluctuation in the observed data. Unequal variability can also make simple comparisons of means less suitable if their assumptions are not met. The phenylephrine standard deviation is 29.32, while the ephedrine standard deviation is 7.23. The record does not give enough detail to determine the causes of this difference or whether it reflects the underlying population, the small groups, or particular observations. Without individual data, readers cannot evaluate outlier influence or alternative summaries.

Over-dispersion is a term used generally when observed variability exceeds what a model assumes. This trial's outcome is continuous, and the record does not identify an over-dispersion model or report that over-dispersion was assessed. It would therefore be inappropriate to claim that over-dispersion was present or addressed. More generally, matching the analysis to the distribution and spread of an outcome matters because model assumptions affect uncertainty estimates and test results.

What can a recalculation add?

A recalculation from summary statistics is generally an unadjusted analysis that depends on the summaries and assumptions available. For this two-arm continuous endpoint, a recalculated comparison is not reported as estimable in the registry record. No recalculated effect estimate, confidence interval, or p-value is available in the registry record for this explanation. The reported group means and standard deviations should not be used to imply an unreported inferential result, especially when the registry's test is rank-based.

The registry entries do not identify a sample-size justification or an analysis plan. A sample-size illustration, where presented, is a planning exercise based on assumptions and an effect to detect; it is not observed power and does not change what the trial's data show. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect defined as a fraction of the observed effect. Those are planning assumptions, not evidence about the original design or a guarantee that a future study would achieve a particular result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Phenylephrine", "Ephedrine")
n   <- c(9, 4)
m   <- c(30.08, 19.1)
sp  <- c(29.32, 7.23)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Phenylephrine  9  30.080  29.320  7.543  52.617
CARM  Ephedrine  4  19.100  7.230  7.595  30.605

11. Analyses Reported by the Sponsor

The sponsor's reported analysis for the primary comparison is a Kruskal-Wallis test, with p = 0.547. The registry also posts arm-level means and standard deviations. These are different kinds of information: the means and standard deviations summarize the observed groups, while the test provides the reported inferential comparison. Because the test is rank-based, its p-value should not be described as a direct test of the difference between those means.

A recalculated two-arm continuous comparison is not reported as estimable in the registry record. There is therefore no recalculated estimate or p-value to set against the sponsor's test. The record does not flag a discrepancy between a sponsor analysis and a recalculation. The sponsor's reported test is the available inferential analysis; the arm summaries remain useful for describing the posted endpoint values but do not replace that test.

The brief summary states that phenylephrine is associated with reductions in cerebral tissue oxygen saturation compared with ephedrine, while the posted primary means are higher for phenylephrine. The record does not explain the difference in direction between that statement and the posted primary endpoint summaries. The analysis should not resolve this inconsistency by favoring an unreported calculation or by treating the brief summary as a substitute for the numerical outcome. Further details of the sponsor's analysis, including its prespecified status, adjustments, and interpretation, are not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 7 analyses, and identifies cardiac output as a secondary outcome. The primary endpoint is cerebral tissue oxygen saturation. The registry entries available for this explanation do not include the complete outcome list, the results for the secondary outcome, or the relationship between all recorded outcome measures and analyses. Those details are not reported in the registry record.

Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are examined. The more opportunities there are to identify a result, the greater the chance that at least one finding may appear notable by chance if no adjustment or other prespecified strategy is used. The record does not report whether multiplicity was addressed, whether outcomes were ordered hierarchically, or whether any outcomes were designated as exploratory. It would be inappropriate to infer either that adjustment was used or that it was omitted from the analysis.

The registry does not report missing-data counts, reasons for missing measurements, or methods for handling missingness. Although outcome summaries list 9 participants in the phenylephrine group and 4 in the ephedrine group, the record does not explain how those analysis counts relate to the enrollment entry of 13. It does not state whether every enrolled participant contributed a primary measurement, whether participants were excluded, or how incomplete intraoperative measurements were treated. These matters are not reported in the registry record.

The analysis population is also not described in the registry entries. The registry does not specify whether the posted comparison follows intention-to-treat, per-protocol, or another population definition. It does not state whether participants were analyzed according to assignment or treatment received. Without that information, the results can be described only as the posted arm summaries and reported test, without assigning them to a particular analysis population.

These omissions matter when interpreting a small trial because outcome selection, missing measurements, and analysis-population decisions can affect what the estimates represent. The record does not allow readers to assess those aspects of the analysis. No conclusion about the presence, extent, or handling of missing data or multiplicity can be drawn from silence in the registry.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The posted adverse-event figures report 0 serious adverse events among 9 participants at risk in the phenylephrine group and 0 among 4 participants at risk in the ephedrine group. The record also reports 0 other adverse events in each group and 0 deaths in each group. No top serious adverse-event terms are listed.

These figures describe what the registry record reports for the stated groups. They are not proof that no adverse events could occur, and they do not establish that the groups have equal safety. In general, when few participants are observed, even an event that is not recorded during a trial may remain possible in a broader population. The available figures also do not give event timing, definitions, severity categories beyond the serious-event classification, or details of how events were collected.

The adverse-event counts are distinct from the primary endpoint analysis. They do not establish the effect of either intervention on cerebral tissue oxygen saturation or cardiac output, and the primary endpoint p-value does not summarize safety. The registry record does not report additional safety methods, follow-up duration for adverse events, or whether the reported figures cover the entire trial period. Interpretation should therefore remain limited to the zero counts and group-specific at-risk figures recorded, without extending them to broader claims about safety.

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

The posted results show group-level primary endpoint summaries for cerebral tissue oxygen saturation during the period from spinal placement until 10 min after delivery. The mean is 30.08 with standard deviation 29.32 in the phenylephrine group and 19.1 with standard deviation 7.23 in the ephedrine group. The reported Kruskal-Wallis test has p = 0.547. These data do not provide strong statistical evidence of a difference under the reported test, but they also do not establish equivalence or rule out a meaningful difference.

The results do not show the precision of a between-group effect because the registry does not report a confidence interval for that comparison. The small arm counts and differing spreads further limit how firmly the group summaries can be generalized. A p-value alone cannot establish the size, direction, or clinical importance of an effect. The record does not report a clinical-importance threshold for this endpoint.

The trial's brief summary says that phenylephrine administration is associated with reductions in cardiac output and cerebral tissue oxygen saturation compared with ephedrine. For the posted primary endpoint, the phenylephrine mean is higher, and the reported comparison has p = 0.547. The record does not explain that difference between the narrative summary and primary endpoint values. The cardiac output result itself is not included in the registry record for this explanation, even though cardiac output is listed as a secondary outcome.

These findings are specific to the recorded trial population, interventions, and intraoperative measurement period. They do not establish what would occur in other settings, under other treatment conditions, or for outcomes not reported in the registry record. Nor do the reported adverse-event counts establish that either intervention is free of risk. The appropriate conclusion is limited: the registry posts these group summaries and this test result, while leaving important questions about precision, missingness, analysis populations, and the secondary outcome unanswered.

The terminated status is part of the registry record, but the reason for termination is not reported. It cannot by itself show whether trial conduct, outcome availability, or analysis decisions were affected. No medical advice or treatment recommendation follows from these statistics.

15. Why This Trial Matters Statistically

This trial illustrates why a numerical result should be read together with its endpoint definition, analysis method, and uncertainty. The primary outcome is a continuous measurement reported as group means and standard deviations, but the reported inferential test is Kruskal-Wallis. A reader should not assume that the p-value directly tests the difference between the displayed means. Keeping descriptive summaries separate from the inferential method helps avoid attributing a result to the wrong statistical quantity.

The example also shows why a non-significant test is not the same as evidence of no effect. The reported p-value is 0.547, and the registry does not provide a confidence interval for the between-group comparison. Without an interval, the range of effects compatible with the results is not directly visible. The trial's small arm counts and the difference in reported standard deviations make precision especially relevant to interpretation, although the record does not provide individual data to examine the distributions.

Another statistical issue is consistency across types of reporting. The brief summary describes reductions in the primary endpoint with phenylephrine, while the posted means place the phenylephrine value higher. An analyst should identify that mismatch rather than silently choose one account or create a new result from incomplete information. The primary test, descriptive summaries, and narrative statement each need to be distinguished.

Finally, the record demonstrates the limits of registry-level interpretation. The status is terminated, but the reason is not reported; missing-data handling, analysis populations, and multiplicity methods are also not reported. Those absences constrain what can be concluded about the conduct and analysis. Transparent reporting of these elements is important because readers need to understand not only the numerical result, but also what data were analyzed and how uncertainty was assessed.

16. 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 most immediate limitation is the small size of the reported endpoint groups: the registry posts 9 participants for phenylephrine and 4 for ephedrine. The record does not explain why these outcome-specific counts appear alongside enrollment of 13, or whether every enrolled participant contributed to the primary analysis. Missing measurements, exclusions, and analysis-population rules are not reported in the registry record.

The primary endpoint summaries include a large standard deviation for phenylephrine relative to its mean and a smaller reported standard deviation for ephedrine. With limited group counts, summary estimates can be sensitive to individual observations. Individual measurements and distribution details are not reported, so outliers, skewness, or the stability of the variability estimates cannot be assessed. The record provides no confidence interval for the primary between-group comparison.

The reported inferential method is Kruskal-Wallis, but the reason for selecting it and its implementation are not described. The registry does not report a full statistical analysis plan, prespecification details, covariate adjustment, or how repeated measurements during the intraoperative period were handled. It also does not report whether multiplicity was addressed across the 8 outcome measures and 7 analyses.

The brief summary and the posted primary endpoint means differ in direction. The record does not explain this inconsistency. Cardiac output is listed as a secondary outcome, but its result is not present in the registry record for this explanation. The registry does not report a threshold for clinical importance for cerebral tissue oxygen saturation.

The trial is listed as terminated, with no reason reported. The registry entries do not state whether termination affected enrollment, follow-up, outcome collection, or analysis. These limitations mean that the posted figures should be read as a limited registry account, not as a complete description of trial conduct or a definitive estimate for a broader population.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Phenylephrine Versus Ephedrine in Pre-eclampsia — NCT02025426.
• Registry record last updated 2020-10-14; status last verified 2020-09.
• Results first posted 2020-10-14.
• 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.

20. Record Summary

The registry describes a phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Duke University, with a terminated status and enrollment of 13. It compares phenylephrine with ephedrine for maintaining blood pressure within 10 % of baseline in women with pre-eclampsia undergoing cesarean delivery under spinal anesthesia.

The primary endpoint is cerebral tissue oxygen saturation, measured from spinal placement until 10 min after delivery. The reported mean and standard deviation are 30.08 and 29.32 for phenylephrine, and 19.1 and 7.23 for ephedrine. The reported Kruskal-Wallis p-value is 0.547. Cardiac output is listed as a secondary outcome, but its result is not reported in the registry record for this explanation.

The record does not report a confidence interval for the comparison, the reason for termination, missing-data handling, analysis-population definitions, or multiplicity methods. The posted primary endpoint test and summaries do not resolve the inconsistency between the registry's brief summary and the direction of the means.