Phenylephrine in Spinal Anesthesia in Preeclamptic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phenylephrine in Spinal Anesthesia in Preeclamptic Patients (NCT00458003), a randomized na study. The primary outcome is The Umbilical Artery pH.

2. Clinical Question

The clinical context in the registry is concern about hypotension after spinal anesthesia in preeclamptic patients and the potential relevance of newborn acid-base status. The record describes prior concerns about phenylephrine and uterine blood flow, alongside the rationale for comparing it with ephedrine. The trial’s primary endpoint was a newborn blood measurement, rather than a direct measure of maternal hypotension. The registry record does not report the operational definition of hypotension used for treatment, the infusion dosing details, or other protocol details beyond the arm descriptions.

3. Trial Design

The registry identifies NCT00458003 as a completed, randomized, double-masked, parallel-group trial. It lists an enrollment of 110 and a phase of NA. Northwestern University is listed as the sponsor. The recorded start is 2006-07 and the primary completion is 2016-12. The two arms were phenylephrine and ephedrine, each described as an infusion to prevent and treat hypotension associated with spinal anesthesia during cesarean delivery.

The primary endpoint was umbilical artery pH immediately after delivery. The arm-level outcome entries list 54 participants in each group, with a median pH of 7.22 and standard deviation 0.07 for phenylephrine, and a median of 7.2 and standard deviation 0.1 for ephedrine. Separately, the primary outcome description says that 72 newborn blood samples in the phenylephrine group and 74 in the ephedrine group were analyzed, and notes multiple gestations in both groups. The record therefore distinguishes the arm-level participant counts from the newborn sample counts; it does not explain further how the outcome analysis handled multiple gestations.

The listed secondary outcome is umbilical artery blood base excess. The registry record does not report a usable two-arm comparison for that endpoint; it states that values were missing or not estimable. The record does not report the randomization method, allocation concealment procedures, masking details, treatment doses, or a protocol-level analysis plan. It also does not report a sample-size justification or interim-analysis plan. These absences limit how completely the trial’s conduct and prespecified design can be assessed from the registry entry alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 72 newborn blood samples in the phenylephrine group and 74 newborn blood samples were analyzed (there were multiple gestations in both groups)

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 The Umbilical Artery pH, measured over Immediately after delivery.

Umbilical artery pH measures the acidity or basicity of blood sampled from the umbilical artery. The registry specifies that the blood pH was measured immediately after delivery and gives a normal range of pH: 7.18 - 7.38. It explains that a lower pH indicates more acidic blood and a higher pH indicates more basic blood. The endpoint is therefore a newborn blood measurement, not a direct measurement of maternal blood pressure or the incidence of maternal hypotension.

The endpoint was used to compare newborn acid-base status between the phenylephrine and ephedrine groups. In general, a physiologic measurement can provide information about a particular biological outcome, but it does not by itself represent every aspect of health or establish why a difference might occur. The registry’s stated clinical rationale includes concern about newborn acidemia in the setting of maternal hypotension and the choice of vasopressor. That context explains why umbilical artery pH was of interest, but it does not make pH a complete measure of maternal or newborn outcomes.

The registry labels the primary parameter as a median and lists standard deviation as its dispersion measure. It reports group medians of 7.22 and 7.2, with standard deviations of 0.07 and 0.1, respectively. It also notes that multiple gestations occurred in both groups and that the analyzed newborn sample counts were 72 and 74. The record does not provide additional details about sample collection, handling of multiple newborns from the same pregnancy, or missing pH measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is reported as a Wilcoxon (Mann-Whitney) test comparing the phenylephrine and ephedrine groups. The outcome is umbilical artery pH immediately after delivery. The registry records the test result as p = .38 and reports group medians with standard deviations. It does not report the test statistic, a confidence interval, a treatment-effect estimate, or additional detail about the exact test implementation.

What does the Wilcoxon (Mann-Whitney) test compare?

In general, the Wilcoxon (Mann-Whitney) test is a rank-based method for comparing observations from two groups. Instead of requiring the comparison to be expressed as a difference between means, it uses the relative ordering of observations across groups. Its interpretation depends on the distributions being compared. It is often described as a test of whether one group tends to have higher or lower observations than the other, but it does not automatically test only whether two medians differ. If distribution shapes differ, a result may reflect more than a shift in the center.

For this trial, the registry identifies the method and p-value but does not report the underlying individual observations or a confidence interval. The listed medians are useful summaries, but they are not sufficient to reconstruct the rank-based test. The p-value should therefore be read as the registry’s reported test result, not as a measure of the size of a pH difference.

How should the median and standard deviation be read?

In general, the median is the middle value after observations are ordered. The standard deviation describes variation around the mean and is most naturally interpreted alongside a mean. These summaries are not interchangeable. The registry labels the primary parameter as MEDIAN and the dispersion as Standard Deviation; it does not explain this choice or provide a distribution plot or other spread summary in the record. The reported values should be quoted as registered, while recognizing that the information does not fully characterize the distribution of newborn pH measurements.

What does a p-value convey?

In general, a p-value measures how unusual data at least as incompatible with a null hypothesis as the observed data would be, if that null hypothesis and the test assumptions were correct. It is not the probability that the null hypothesis is true, the probability that chance alone caused the findings, or a measure of clinical importance. Here, p = .38 is the result reported for the Wilcoxon (Mann-Whitney) comparison. Without a confidence interval or a treatment-effect estimate, the record does not show a range of values compatible with the data or directly quantify the uncertainty around the group contrast.

Why do the sample counts matter?

The arm summaries list 54 participants in each group. The primary outcome description says that 72 newborn blood samples in the phenylephrine group and 74 in the ephedrine group were analyzed, and notes multiple gestations in both groups. In general, when more than one outcome observation can come from a participant or pregnancy, analyses may need to account for the relationship among observations. Treating related observations as independent can make standard errors and confidence intervals misleading. The registry record does not report whether or how the analysis accounted for multiple gestations, so the statistical handling of this feature cannot be assessed from the entry.

What is not reported about the analysis?

The registry record does not report the statistical analysis plan, analysis population, handling of missing pH values, assumptions used in the test, or a confidence interval for the primary comparison. It does not report a usable two-arm result for the secondary base-excess endpoint, with values described as missing or not estimable. It also does not report whether any multiplicity adjustment was applied. These omissions prevent a complete assessment of how the reported analysis was selected, how robust it may be to missing observations, or how the primary result relates to the additional endpoint.

The record includes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such estimates are planning aids for future studies, not observed power and not additional results from this trial. The record does not report that this illustration was the trial’s original sample-size justification. In general, planning estimates depend on their assumptions and should not be read as evidence about the probability that the completed trial detected a true effect.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a Wilcoxon (Mann-Whitney) test, with p = .38. It also reports the arm summaries as medians and standard deviations. No confidence interval or numerical treatment-effect estimate is included in the registry record, so the sponsor’s result does not give a directly reported range for the between-group effect.

The record does not identify a competing sponsor analysis or report a recalculated numerical result for this primary comparison. Accordingly, there is no reported discrepancy between a sponsor analysis and a separate recalculation to explain. A simple re-analysis from summary statistics would not reproduce the rank-based test without the underlying observations and relevant analysis details. In general, summary-statistic recalculations may use different assumptions or target a different quantity than the sponsor’s test; they should not be treated as the sponsor’s analysis.

The sponsor-reported test and the posted summary values are the available numerical evidence for the primary endpoint in the registry entry. The record does not report the test statistic, analysis population, confidence interval, missing-data approach, or handling of multiple newborn samples from pregnancies with multiple gestations. Those details would be needed for a fuller assessment of the analysis and its precision.

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is umbilical artery pH. The registry also lists umbilical artery blood base excess as a secondary outcome. It reports that values for the other endpoint were missing or not estimable for a two-arm comparison, so a secondary between-group result is not available in the record. The registry lists two outcome measures and two analyses, but it does not provide enough detail to establish the full relationship between each analysis and the outcome measures.

When a study evaluates more than one outcome or makes multiple statistical comparisons, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures are sometimes used to control that issue, depending on the prespecified analysis strategy and the intended interpretation of the outcomes. The registry record does not report whether a multiplicity adjustment was planned or applied, nor does it provide a statistical analysis plan. The primary p-value should therefore be understood as the reported test result, without assuming a particular multiplicity approach.

The record does not report how missing primary outcome measurements were handled, whether all randomized participants were included in the analysis, or how the analyzed population was defined. It lists 54 participants in each arm and reports 72 and 74 newborn blood samples for the primary endpoint, with multiple gestations in both groups. These counts are not interchangeable, and the record does not explain how the analysis dealt with multiple newborns from the same pregnancy. It also does not report whether any outcome data were excluded or imputed.

The registry record does not report interim analyses, stopping rules, or a prespecified sample-size justification. Those omissions do not establish that such procedures were or were not used; they mean the relevant details are not reported in the registry record. Without the analysis plan and missing-data details, readers cannot determine whether the posted result reflects the full planned analysis strategy or assess sensitivity to alternative analysis choices.

12. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fetal hypoxia (37.5%).

The registry’s adverse-event entries distinguish serious events from other adverse events and list deaths separately. For mothers, the record reports zero serious adverse events among 54 in the phenylephrine group and zero among 54 in the ephedrine group. It also reports 21 other adverse events among 54 phenylephrine mothers and 28 among 54 ephedrine mothers. For infants, it reports 27 serious adverse events among 72 in the phenylephrine group and 25 among 74 in the ephedrine group, with zero other adverse events recorded in either group. Deaths are reported as zero in all four listed groups.

The registry lists “Fetal Hypoxia” as a top serious adverse-event term, with 37.5%. The record does not clarify the precise denominator or further context for that percentage, so it should not be interpreted as a group-specific rate. These registry counts describe recorded events; by themselves, they do not establish that an event was caused by an assigned infusion or show the comparative risk with statistical precision. The record does not provide confidence intervals or a detailed event definition in this entry.

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

The registry record shows that the primary endpoint was newborn umbilical artery pH measured immediately after delivery. It reports a median of 7.22 with standard deviation 0.07 for phenylephrine and a median of 7.2 with standard deviation 0.1 for ephedrine. The sponsor-reported Wilcoxon (Mann-Whitney) test gave p = .38. These registry entries describe the posted summaries and test result; they do not establish equivalence, prove the absence of a difference, or quantify a precise range of plausible group effects.

In general, interpretation of a trial result depends on more than a p-value. Effect estimates, confidence intervals, outcome distributions, analysis populations, and protocol details help show both the magnitude and precision of a comparison. The registry record does not report a confidence interval or numerical effect estimate for the primary comparison. It also does not report how multiple newborn samples from pregnancies with multiple gestations were handled, even though such gestations are noted in both groups.

The primary endpoint is one newborn blood measurement and should not be treated as a complete summary of maternal or newborn health. The registry also lists umbilical artery blood base excess, but a two-arm result is not available because values are described as missing or not estimable. Safety entries list adverse events by maternal and infant groups, but the record does not provide enough detail to infer causation or a precise comparative safety effect.

Accordingly, the posted information supports a narrow reading: it documents the trial design, the pH summaries, and the sponsor-reported statistical test. It does not, on its own, settle broader questions about treatment effects, clinical importance, or outcomes not adequately reported in the registry record. The general statistical point is that a non-small p-value cannot establish that two treatments have the same effects; evidence of equivalence would require an appropriate design and analysis, which are not reported.

14. Why This Trial Matters Statistically

This trial is statistically noteworthy because its primary outcome is recorded at the newborn level while the arm summaries are expressed as participants. The registry lists 54 participants in each group and reports 72 and 74 newborn blood samples, noting multiple gestations in both groups. In general, when observations are clustered within a pregnancy, statistical methods may need to account for their dependence. The registry record does not report whether this was addressed, leaving an important question about the analysis unit and precision.

The endpoint summaries also pair medians with standard deviations, while the primary test is rank-based. These choices can be reported together, but each describes different statistical features. In general, a median and standard deviation do not fully convey the distributional information used by a rank-based test. The registry does not provide further distributional summaries or a confidence interval, limiting interpretation of both the magnitude and precision of the comparison.

The record illustrates why a p-value alone is not enough to judge a clinical comparison. The reported p = .38 is a test result, not a measure of effect size, equivalence, or clinical relevance. A confidence interval or an effect estimate would add information about uncertainty, but neither is reported for the primary comparison. The unavailable secondary base-excess comparison further limits the outcomes that can be assessed from this entry.

Finally, the registry gives useful information about randomization, masking, the parallel design, interventions, and enrollment, but several analysis details are not reported. This includes the analysis population, missing-data handling, multiplicity approach, and any prespecified sample-size justification. The case demonstrates how statistical interpretation depends on clear reporting of both the outcome summaries and the methods used to analyze them.

15. 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 entry does not report a confidence interval or an effect estimate for the primary comparison. The p-value and arm summaries therefore do not show the precision of the group contrast. The outcome is labeled as a median with standard deviation, and the record does not explain the summary choice or provide further information about the outcome distributions.

The primary outcome description reports newborn blood sample counts of 72 and 74, whereas the arm-level summaries list 54 participants in each group. Multiple gestations are noted in both arms. The registry does not report how observations from newborns in the same pregnancy were handled, whether the analysis accounted for their possible dependence, or how the discrepancy between participant and sample counts relates to the analysis population.

Other analysis details are also not reported in the registry record: the statistical analysis plan, randomization procedure, allocation concealment, masking procedures, dosing details, missing-outcome handling, and analysis population. The record does not report whether multiplicity adjustments or interim analyses were used, or the trial’s original sample-size justification. These are reporting limitations; their absence from the entry does not establish what procedures were or were not followed.

The secondary base-excess outcome has no reported two-arm comparison because values are described as missing or not estimable. The adverse-event listing includes counts and a top serious-event term, but it does not provide detailed definitions, confidence intervals, or enough context to assess causation. Taken together, these omissions restrict interpretation to the outcomes and statistics explicitly recorded, rather than allowing a comprehensive assessment of the trial’s conduct or all possible benefits and harms.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phenylephrine in Spinal Anesthesia in Preeclamptic Patients — NCT00458003.
• Registry record last updated 2022-06-02; status last verified 2022-05.
• Results first posted 2022-06-02.
• 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.

19. Record Summary

NCT00458003 is a completed, randomized, double-masked, parallel-group trial sponsored by Northwestern University. It compared phenylephrine and ephedrine infusions intended to prevent and treat spinal anesthesia-associated hypotension during cesarean delivery in preeclamptic patients. The registry lists enrollment of 110, a start date of 2006-07, and primary completion in 2016-12.

The primary endpoint was umbilical artery pH immediately after delivery. The registry reports median pH values of 7.22 for phenylephrine and 7.2 for ephedrine, and a Wilcoxon (Mann-Whitney) test result of p = .38. It does not report a confidence interval for the comparison. Umbilical artery blood base excess is listed as a secondary outcome, but its two-arm values are missing or not estimable. The record also reports maternal and infant adverse-event counts, while leaving important analysis details unreported.