Neuraxial Preservative Free Morphine for Normal Spontaneous Vaginal Delivery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neuraxial Preservative Free Morphine for Normal Spontaneous Vaginal Delivery (NCT04017442), a randomized phase 4 study. The primary outcome is Opioid Consumption in MME.

2. Clinical Question

The trial also lists outcomes concerning pain, obstetric quality of recovery, postpartum depression screening, and exclusive breastfeeding. These outcomes broaden the questions the study set out to examine, but the registry record does not post numerical results for all of them. The interpretation therefore centers on the primary opioid-consumption measure and distinguishes that descriptive result from the limited secondary results available.

The clinical question is specifically about opioid consumption in the short period after delivery. It is not a direct measure of pain relief, longer-term opioid use, recovery in general, or the later outcomes listed in the record. The available summary also does not describe participant characteristics or the reasons a clinician might select one intervention rather than another; the randomized design, rather than a detailed account of clinical context, is the basis for understanding the comparison.

3. Trial Design

This was a prospective, randomized, parallel-group trial described in the official title as double blind. The registry lists quadruple masking. It does not identify which people or roles were masked, or provide details about allocation concealment, the randomization sequence, or how masking was maintained. The study is listed as phase 4 and completed.

The planned enrollment was 160. The posted primary outcome includes 80.0 participants in the morphine group and 77.0 in the saline group. These outcome counts do not by themselves explain how participants moved through the trial, whether every randomized participant contributed outcome data, or why the counts differ. Participant flow and the handling of missing outcomes are not reported in the registry record.

Patients presenting for normal spontaneous vaginal delivery with neuraxial anesthesia were to receive preservative-free morphine or saline after delivery. The arm descriptions specify 2mg morphine and 4 mL saline. The record does not give a more detailed account of the administration procedure, timing beyond after delivery, or any additional care procedures.

The registry lists a start date of 2019-10-19 and a primary completion date of 2023-08-31. It lists opioid consumption in MME within 24 hours of delivery as the primary outcome. Four secondary outcomes are also listed: pain score, the Obstetric Quality of Recovery Score (OBSQ10), participants with Edinburgh Postnatal Depression Scale (EPDS) >10, and exclusive breastfeeding. Although the record lists five outcome measures overall, it contains no reported analysis entries. A sample-size justification for the trial, a detailed statistical analysis plan, and planned interim analyses are not reported in the registry record.

The parallel randomized structure makes the intended comparison one between the two assigned groups. The summary does not specify an allocation ratio, and no such ratio should be inferred from the outcome counts. Nor does the record establish whether the posted summaries follow an intention-to-treat, per-protocol, or other analysis population.

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:

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 Opioid Consumption in MME, measured over within 24 hours of delivery.

The primary endpoint is opioid consumption, expressed in morphine milligram equivalents, within 24 hours of delivery. MME is a way to express quantities of different opioids on a common scale. This lets a summary describe combined opioid use even when participants may receive different opioid medicines.

The registry describes conversions used for the endpoint: 2 mg oral hydromorphone is treated as 8 MME, and 5 mg oxycodone as 7.5 MME. It also describes converting intravenous hydromorphone to morphine using a 4:1 ratio, followed by a 1:3 ratio to convert intravenous to oral. Those rules form part of how the recorded outcome was constructed; the registry does not provide further detail about all medication records or calculation procedures.

Consumption is relevant to the trial’s stated question because it measures opioid use during a defined period after delivery. It is distinct from a pain score: use can be influenced by pain, prescribing and administration practices, participant preferences, and other factors. The endpoint therefore describes medication consumption, not pain itself or a complete account of recovery.

The primary measure is reported as a median and full range. A median summarizes the center of observed values without being determined by unusually high values in the same way as a mean. The full range shows the lowest and highest posted values, but does not show how observations are distributed between those endpoints. The record does not post a confidence interval or a sponsor-reported comparative estimate for this primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry is limited. It identifies the trial as randomized, parallel-group, and quadruple-masked, and gives a primary endpoint summarized by median and full range. It does not post a statistical analysis plan or reported analysis entry. The explanations below distinguish the general meaning of the summaries from what can be established about this particular trial.

What does a median summarize?

In general, the median is the middle observation after values are ordered. It is a measure of location, not a measure of how spread out all observations are. It can be useful when outcome values are skewed or include unusually large observations, since extreme values do not pull the median in the same way they can pull a mean. That general advantage does not make the median a complete description: two groups can have the same median and different distributions.

Here, the registry gives each group a median of 0.0 MME and also gives a full range. The range describes only the lowest and highest posted values. It does not report quartiles, the number of zero-use participants, or a graphical distribution in the registry record for this explanation. Thus, it is not possible to tell from the range alone whether the values are concentrated near zero or spread across the interval.

What does a comparison estimate add?

For a comparative question, an estimate of the difference between groups is generally more informative than separate summaries alone. It describes the magnitude and direction of a contrast on a stated scale. A confidence interval gives a range of values compatible with the data and the method used, under the assumptions of that method. In general, a narrow interval indicates greater precision than a wide interval; an interval spanning values on both sides of no difference leaves uncertainty about the direction of the contrast.

The primary result does not include a posted comparative estimate or confidence interval. Because the endpoint is reported as a median with full range and no primary analysis is listed, the reader cannot infer a formal comparison or its precision from the two medians. A difference between range endpoints is not a substitute for a treatment-effect estimate: the range reflects extremes and is sensitive to the most unusual observed values.

How should the secondary risk difference be read?

For the EPDS screening outcome, the registry posts a risk difference, an interval, and an unadjusted p-value. In general, a risk difference compares the proportions with an outcome between two groups on an absolute scale. A confidence interval communicates uncertainty around that estimate, while a p-value describes how unusual the observed data would be under a specified null model and its assumptions. A p-value does not give the probability that a hypothesis is true, the probability that chance alone caused the result, or the size or clinical importance of an effect.

The EPDS p-value is posted as unadjusted. That means the record does not show that it was adjusted to account for examining multiple outcomes or comparisons. The posted confidence interval spans values on either side of no difference, so it does not resolve the direction of the association. This is a secondary result; it does not fill the gap in the primary endpoint analysis.

Why can skew and over-dispersion matter?

As a general statistical matter, consumption outcomes can be asymmetric: many observations may be near zero while a smaller number are larger. A mean-based method that assumes a simple symmetric distribution may fit such data poorly. Count outcomes can also be over-dispersed, meaning that their variability exceeds what a basic count model expects. Analysts may then use methods that accommodate the observed distribution, or present robust summaries and uncertainty estimates.

These are general considerations, not claims about the distribution or model used in this trial. The registry does not report participant-level data, a model for the primary outcome, a distributional assessment, or a method for handling over-dispersion. It would therefore be inappropriate to attribute a particular modeling choice to the investigators.

What do the planning illustrations represent?

The sample-size section contains planning illustrations based on the observed EPDS effect. The registry’s stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation, with alternative planning scenarios based on fractions of the observed effect. These are hypothetical calculations for future planning, not the design justification for this trial and not observed power.

Using an effect estimated from a small study as a planning input can produce unstable illustrations. In general, observed effects are uncertain, and a planning exercise based on them does not establish that the original study had adequate power. The registry does not report the trial’s own sample-size assumptions, target effect, or justification. The planning table should therefore be read as an illustration under stated assumptions, not as evidence about what the trial was designed to detect.

More broadly, randomization supports a planned group comparison, but interpretation still depends on complete outcome ascertainment, appropriate analysis, and clear reporting of the analysis population. The registry record does not supply those details for the primary endpoint. The posted summaries can be described, but the methods needed to assess their uncertainty and robustness are not available.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and four secondary outcomes. The record does not report a statistical analysis plan describing how these outcomes were prioritized, whether secondary analyses were confirmatory or exploratory, or how multiplicity was to be handled. It does not report a family-wise error procedure, a hierarchical testing sequence, or another adjustment strategy. The posted EPDS comparison is explicitly unadjusted.

Multiplicity matters because repeated testing can increase the likelihood of seeing a result that appears notable even when there is no underlying effect. This general concern does not mean that any particular result is false; it means that an unadjusted secondary result should be interpreted cautiously, especially when the analysis plan and full set of results are not available.

Missing-data procedures are not reported in the registry record. The record does not describe how missing endpoint values were identified, whether they were imputed, how sensitivity analyses were performed, or whether missingness was considered in the analysis. The primary outcome counts are 80.0 in the morphine group and 77.0 in the saline group, while planned enrollment is 160. Those figures alone do not reveal the number or reasons for missing observations, nor do they establish which participants were included in each analysis.

The analysis population is also not reported. The record does not say whether participants were analyzed according to randomized assignment, treatment received, or another rule. It does not describe exclusions after randomization or provide a participant-flow account. These details matter because they affect the interpretation of a randomized comparison, particularly if participants lack outcome data or do not follow their assigned intervention.

Finally, no primary analysis entry is posted. The registry record does not report interim analyses, covariate adjustment, sensitivity analyses, or a protocol-based sample-size justification. Their absence from the record means these methods cannot be evaluated; it is not a basis for assuming which methods were or were not used outside the posted record.

11. 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 5% reporting threshold.

The posted adverse-event summaries list zero serious adverse events and zero other adverse events in each group. The group counts at risk are 80 for morphine and 77 for saline, and deaths are listed as zero in both groups. These are the figures recorded for the trial’s adverse-event summary.

A zero count in a registry summary means that no events of that category are posted for the listed group; it does not establish that the intervention has no risks. The record does not give event definitions, the period over which events were collected, the method of surveillance, or additional detail about how events were classified. It also does not provide enough information to evaluate how completely safety events were ascertained.

These safety figures should therefore be read as a limited descriptive account, not as a comprehensive safety assessment. They do not alter the interpretation of the primary opioid-consumption endpoint, and they do not establish comparative safety beyond the adverse-event entries shown.

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

The result shows that the posted median opioid consumption within 24 hours of delivery was 0.0 MME in both randomized groups. It also shows that the reported full ranges extended above zero in both groups, with different upper endpoints. That is the extent of the primary result that can be stated directly from the registry summaries.

It does not show that every participant used no opioids, that the group distributions were alike, or that the two interventions are equivalent. Equal medians do not establish equivalence, and the record provides neither a prespecified equivalence margin nor a primary comparative estimate with an uncertainty interval. The ranges alone cannot fill that gap.

The result also does not establish whether the interventions differ in pain, quality of recovery, postpartum depression screening, or breastfeeding. Those are separate outcomes. The registry lists them, but does not post numerical results for all of them. The available secondary comparison is not a substitute for a complete, prespecified analysis of the primary outcome.

More generally, a clinical trial result is best understood through its estimate, uncertainty, analysis methods, and completeness of outcome reporting. Here, the registry provides a concise descriptive primary summary but no reported primary analysis entry. Missing-data handling, analysis population, and the trial’s statistical plan are not reported. These gaps limit the conclusions that can be drawn from the posted record.

The trial is a randomized comparison, which gives its design a clear intended contrast between morphine and saline. However, the design label does not independently resolve limitations in the available reporting. The posted data do not justify a recommendation about treatment or a claim that one intervention works or does not work. They support a descriptive account of the observed summaries and a recognition that the comparative effect remains uncertain in this record.

13. Why This Trial Matters Statistically

This trial illustrates a common statistical distinction: a clear clinical question does not guarantee that the posted results answer it with equal clarity. The primary endpoint is defined in a clinically interpretable way—opioid consumption in MME during a specified period—but the registry presents medians and ranges without a primary comparative estimate or uncertainty interval.

The equal reported medians may look straightforward, yet they do not tell the reader how values are distributed or how precisely the groups differ. The ranges add information about observed extremes, but do not describe the pattern between them. This is why endpoint summaries and a treatment-effect analysis serve different purposes.

The record also shows why secondary findings need context. A trial can list several outcomes that matter to different domains, but incomplete results and unadjusted comparisons make it difficult to judge a coherent pattern. Multiplicity, analysis populations, missing outcomes, and prespecification are not technical afterthoughts: they determine how confidently findings can be interpreted.

Finally, the planning illustrations show how sample-size calculations depend on assumptions about the effect to be detected and the design. They are not observed power and do not replace a trial-specific design justification. Keeping planning exercises separate from the trial’s observed results is essential for sound interpretation.

14. 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 important limitation for interpreting this trial from the registry record is the absence of a reported primary comparison. The primary endpoint is summarized by group, but there is no posted estimate of the difference, confidence interval, or inferential analysis. The equal medians therefore cannot establish equivalence or quantify the precision of a group contrast.

The median and full range offer limited detail about the distribution of opioid consumption. The record does not provide quartiles, the number of participants with zero use, or participant-level values. Without those summaries, the variability and shape of the outcome cannot be assessed fully.

There is also limited information about the study population and trial conduct. Eligibility details, participant characteristics, allocation concealment, masking roles, protocol adherence, and participant flow are not reported in the registry record. The outcome counts do not explain the difference between the posted group sizes or identify the analysis population.

Missing-data handling, the statistical analysis plan, the trial’s sample-size justification, and any interim analyses are not reported. For secondary outcomes, numerical results are not posted for all listed measures, and the EPDS comparison is unadjusted. These reporting gaps limit both the completeness of the outcome picture and the assessment of how analyses were selected.

Safety interpretation is also constrained by the absence of event definitions, surveillance details, and a stated observation period. The zero event counts describe the posted summary, but cannot establish the absence of risk. Together, these limitations mean the record supports a narrow descriptive reading rather than a comprehensive evaluation of comparative effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Neuraxial Preservative Free Morphine for Normal Spontaneous Vaginal Delivery — NCT04017442.
• Registry record last updated 2024-08-14; status last verified 2024-07.
• Results first posted 2024-08-14.
• 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.

18. Record Summary

The registry record describes a completed phase 4, randomized, parallel-group trial with quadruple masking and planned enrollment of 160. It compares 2mg preservative-free morphine with 4 mL preservative-free saline after delivery among patients presenting for normal spontaneous vaginal delivery with neuraxial anesthesia. The listed primary outcome is opioid consumption in MME within 24 hours of delivery.

The posted primary summaries report a median of 0.0 MME in both groups, with full ranges of 0.0 to 47.5 MME for morphine and 0.0 to 72.0 MME for saline. The registry contains no reported analysis entries, and a primary comparative estimate is not posted. Several secondary outcomes are listed, but numerical results are not available for all of them. The record does not report the analysis plan, missing-data methods, or trial-specific sample-size justification.