Prophylactic Methylergonovine for Twin Cesarean: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prophylactic Methylergonovine for Twin Cesarean (NCT05772156), a randomized phase 4 study. The primary outcome is Change in Maternal Hemoglobin Level.

2. Clinical Question

The trial asks whether an injection of prophylactic methylergonovine immediately after delivery is associated with a different change in maternal hemoglobin after scheduled cesarean delivery for a twin pregnancy than an injection of matching placebo. Its primary outcome is the change in hemoglobin from the preoperative baseline to postoperative day one, described in the registry timeframe as approximately 48 hours.

This is a comparison of assigned groups, not a comparison of patients selected according to whether they later needed additional treatment. Random assignment is intended to make the groups comparable on average, although it cannot guarantee balance in a trial of this size. The posted results report 33 participants in each group. They show a mean hemoglobin change of 1.1 g/dL in the methylergonovine group and 2.1 g/dL in the placebo group. The contrast is reported as a mean difference of -1.0 g/dL, with a confidence interval and p-value shown in the results. Those estimates describe the trial participants and the registry’s stated outcome; they do not establish how the result would apply to other populations or settings.

3. Trial Design

The registry describes this as a Phase 4 randomized controlled trial with a parallel-group design and double masking. The study title focuses on prophylactic methylergonovine in patients undergoing cesarean delivery with twin gestations. The intervention was prophylactic methylergonovine, described as 200mcg IM; the comparator was a matching placebo. The study summary says the assigned injection was given immediately after delivery. The registry record lists Columbia University as sponsor.

The record reports enrollment of 66 and lists the study as completed. It gives a study start date of 2023-03-07 and a primary completion date of 2024-03-03. The posted primary outcome includes 33 participants in each group. The registry summary frames the clinical question around blood loss in scheduled twin cesarean deliveries, while the primary outcome actually posted is change in maternal hemoglobin from baseline to postoperative day one. The primary-outcome timeframe is described as baseline and postoperative day one, approximately 48 hours.

Randomization assigns participants to groups by chance, rather than by clinical characteristics or treatment choice. In general, this helps reduce systematic differences between groups at the point of assignment. Double masking means the registry classifies the trial as masked at two levels, but the identities of the masked parties and the procedures used to maintain masking are not reported in the registry record. The precise randomization procedure, allocation concealment, eligibility criteria, participant flow, and analysis population are also not reported in the registry record.

The registry identifies 19 outcome measures and lists secondary outcomes such as surgical time, estimated blood loss, quantitative blood loss, postpartum hemorrhage, and use of additional interventions. The posted results include the primary hemoglobin outcome and selected secondary outcome summaries. The record does not report the original design’s sample-size justification or a detailed statistical analysis plan. The planning illustrations elsewhere on this page are based on observed effects and should not be mistaken for the trial’s original design rationale.

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 Change in Maternal Hemoglobin Level, measured over Baseline and Postoperative Day 1 (Approximately 48 hours).

The primary endpoint is the change in maternal hemoglobin level, measured in g/dL. The registry says the change is calculated from preoperative day one, used as baseline, to postoperative day one. The timeframe is described as approximately 48 hours. Hemoglobin is a blood measurement that can reflect changes following delivery and blood loss, so comparing the change between randomized groups offers a way to assess whether the groups had different average postoperative changes. It is not itself a direct measurement of blood volume lost.

The endpoint is summarized as a mean with a standard deviation. A mean gives the average change within a group; the standard deviation describes the spread of individual measurements around that group average. The registry reports a mean change of 1.1 g/dL with a standard deviation of 0.7 in the methylergonovine group, and 2.1 g/dL with a standard deviation of 0.9 in the placebo group. The posted comparison expresses the group contrast as a mean difference of -1.0 g/dL.

The endpoint is relevant to the study’s stated interest in bleeding, but interpretation depends on the exact timing and method of blood sampling and on how missing measurements were handled. Those details are not reported in the registry record. The record’s wording describes the change from baseline; it does not provide additional detail about the sign convention beyond the posted group means and contrast.

7. Results Posted in the Registry

• Prophylactic Methylergonovine: mean 1.10 versus 2.10 on control; difference -1.00 (95% CI -1.39 to -0.61), standardized effect d = -1.24; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Postpartum Hemorrhage

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Prophylactic Methylergonovine: 18.2% (6/33) versus 54.5% (18/33) on control; risk difference -36.4 percentage points (95% CI -57.9 to -14.9), risk ratio 0.33 (0.15–0.73); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Prophylactic Methylergonovine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Requiring Use of Uterotonics

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Prophylactic Methylergonovine: 0.0% (0/33) versus 18.2% (6/33) on control; risk difference -18.2 percentage points (95% CI -31.3 to -5.0); unadjusted two-proportion z-test p = 0.010.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Prophylactic Methylergonovine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Requiring Use of Tranexamic Acid

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Prophylactic Methylergonovine: 6.1% (2/33) versus 21.2% (7/33) on control; risk difference -15.2 percentage points (95% CI -31.3 to 1.0), risk ratio 0.29 (0.06–1.27); unadjusted two-proportion z-test p = 0.073.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Prophylactic Methylergonovine and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results generally point in the same direction as the primary comparison: the posted event counts for postpartum hemorrhage, need for uterotonics, and need for tranexamic acid are lower in the methylergonovine group than in the placebo group. The strength of the statistical evidence is not uniform across these outcomes. The confidence interval for the tranexamic-acid risk difference includes zero, while the reported intervals for the other two outcomes lie below zero. The tables present the counts and estimates, so this discussion focuses on how to read their overall pattern rather than repeating each result.

These outcomes relate to the primary hemoglobin result because they describe clinical events or additional treatments connected to bleeding management, whereas the primary endpoint measures change in a blood marker. Agreement across distinct measures can add context, but the outcomes do not measure the same thing and should not be treated as interchangeable confirmation. Blood-loss measures and treatment decisions may also have different sources of variation and different definitions. The registry lists other secondary outcome categories, including surgical time, estimated blood loss, and quantitative blood loss, but detailed interpretation depends on the particular measure and its posted results.

The secondary comparisons are labeled unadjusted, and the registry record does not report a multiplicity plan. When researchers examine multiple outcomes, the chance of seeing an apparently notable result by chance can increase. This general concern means that unadjusted secondary p-values carry less weight than a result from a clearly prespecified primary test, particularly when the testing hierarchy and analysis plan are not reported. These findings are useful for describing the trial’s pattern, but they should not be treated as independent definitive tests.

There are also limits to how much can be inferred from event counts in a trial with 33 participants per group. Counts can be sensitive to a small number of cases, and the registry record does not provide all definitions or adjudication details for these outcomes. The secondary results are best considered alongside the primary estimate, their own intervals, and the study’s reporting gaps.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Surgical Time
• Estimated Blood Loss
• Quantitative Blood Loss
• Number of Participants With Postpartum Hemorrhage
• Number of Participants Requiring Use of Uterotonics
• Number of Participants Requiring Use of Tranexamic Acid
• Number of Participants Requiring Use of Open-Label Methylergonovine
• Number of Participants Requiring Transfusion (Intraoperative)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports the primary outcome as a continuous measurement: change in maternal hemoglobin level, expressed in g/dL. A continuous outcome can take a range of values rather than representing only whether an event occurred. The posted group summaries are means and standard deviations. The mean describes the average change for participants in a group. The standard deviation describes how dispersed the individual measurements are around that average; it is not the uncertainty in the mean itself.

What does the mean difference represent?

The primary comparison is reported as a mean difference of -1.0 g/dL for prophylactic methylergonovine relative to placebo. In general, a difference between group means is formed by subtracting the comparator group mean from the intervention group mean. Here the posted means are 1.1 g/dL and 2.1 g/dL, respectively, and the registry comparison gives the resulting direction and estimate. The negative sign indicates that the intervention-group mean is lower than the placebo-group mean under this ordering. The difference summarizes groups; it does not mean every participant had a change of that amount.

Why report a standard deviation?

Group means alone do not show how much participant measurements vary. The reported standard deviations, 0.7 and 0.9, give a description of within-group spread. A standard error, by contrast, describes the sampling uncertainty of an estimated mean. The registry’s comparison details include standard errors for the two group means, but do not describe the full analytic procedure that generated them. In general, separating spread among individuals from uncertainty in a group estimate helps readers avoid treating the standard deviation as if it were a confidence interval.

How should the p-value be read?

The primary result includes an unadjusted p-value of < 0.001. In general, a p-value assesses how unusual data at least as extreme as those observed would be under a specified null hypothesis and analysis model. It does not give the probability that a treatment effect exists, and it is not a measure of clinical importance. The reported p-value is unadjusted: the registry record does not state that it accounts for testing multiple endpoints or comparisons. The statistical model, any covariate adjustment, and the planned testing procedure are not reported in the registry record.

What does the standardized effect add?

The registry comparison also reports a standardized effect value of -1.24. Standardizing a mean difference expresses it relative to a measure of variability, which can help place an effect on a scale that is less dependent on the original measurement units. This type of value does not replace the mean difference in g/dL, which remains easier to interpret in the endpoint’s original units. The registry record does not describe which standardized-effect convention was prespecified or used, so the value should be read as a posted summary rather than as evidence of a particular analysis plan.

What can be learned from binary secondary outcomes?

Some secondary outcomes are counts of participants with an event, such as postpartum hemorrhage, or participants requiring an additional intervention. For such outcomes, the group summaries are event counts among the participants shown. A risk difference describes the difference between the group event proportions, with its sign depending on the comparison order. In general, a confidence interval around a risk difference conveys uncertainty about that contrast. For the posted secondary comparisons, some intervals include zero and others do not. These results are unadjusted, and they should not be treated as if the trial had a single prespecified confirmatory test for each one unless that plan is documented. The registry does not report such a plan.

Why can trial size affect interpretation?

Statistical estimates are influenced by both the effect size and the amount of information in the data. A trial with relatively few participants may produce less precise estimates, particularly for outcomes that occur infrequently. Randomization helps guard against systematic allocation differences in expectation, but a modest enrollment does not ensure that all relevant characteristics are balanced. The posted primary outcome includes 33 participants per group; the registry record does not provide enough information to determine how many participants were randomized, excluded, or missing from each analysis.

The trial’s own original sample-size assumptions, statistical analysis plan, interim analyses, missing-data procedures, and analysis-population definitions are not reported in the registry record. This is distinct from the planning illustrations elsewhere on this page, which use observed effects and stated generic assumptions. Those illustrations are not a substitute for the design decisions made before enrollment. Without the original plan, readers cannot verify whether the primary analysis, endpoint timing, and secondary testing were conducted as intended.

In general, statistical significance and precision are related but different considerations. A small p-value does not eliminate uncertainty about the effect’s magnitude, while a confidence interval helps display a range of estimates compatible with the observed data under the method used. The posted primary interval is wholly below zero; the secondary intervals vary. How these estimates should influence a broader evidence assessment depends on study conduct, endpoint quality, and other evidence, several details of which are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -1.0 g/dL, with a confidence interval from -1.389 to -0.611. The interval lies on the negative side of zero for the stated comparison direction. It communicates uncertainty around the estimated group difference: values across the interval are more compatible with the data than values far from it under the interval’s method. A confidence interval does not mean that the true effect has a particular probability of falling inside this one calculated interval. The confidence level and interval-construction method are not reported in the registry record.

The p-value for the primary comparison is < 0.001. This is consistent with the interval not including zero, but the p-value and interval answer different questions. The p-value summarizes compatibility with a null hypothesis under an analysis model; the interval emphasizes the range of estimates compatible with the data under its method. Neither alone establishes clinical importance or guarantees that a similar estimate would be observed in another trial.

The secondary-outcome intervals illustrate why precision matters. For postpartum hemorrhage, the reported risk-difference interval is -0.579 to -0.149. For use of uterotonics, it is -0.313 to -0.050. For use of tranexamic acid, it is -0.313 to 0.01, which includes zero. These intervals should be interpreted alongside the group counts and the unadjusted status of the comparisons. Their width reflects uncertainty, and results for less frequent outcomes can be particularly imprecise.

All of these estimates come from a trial whose primary results include 33 participants in each group. The registry record does not report details such as missing observations or the exact statistical methods used to form the intervals. Those gaps limit independent assessment of precision. The figures displayed in the results should therefore be read as estimates with uncertainty, not as exact measurements of an underlying effect.

12. 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 sample-size section is a planning illustration based on the observed effects, not the trial’s original design calculation. For the continuous primary outcome and the binary secondary outcomes with planning entries, the figures are participants per arm. They are not total enrollment figures. The sample-size assumptions stated for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column describes the planned number of participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and assumptions were correct. The 90% power column describes the corresponding planning target for a 90% chance. These are design probabilities under a model, not probabilities that the posted trial result is true. The entries are illustrations for future planning, not a retrospective score of this completed trial.

Rows that plan for 100%, 75%, and 50% of the observed effect show how the target effect size changes the planning requirement. A smaller effect is harder to distinguish from random variation, so detecting a smaller effect generally requires more participants. The curve should be read as a visual presentation of the planning relationship, not as additional trial results. It does not show observed power, and this is not observed power.

For time-to-event outcomes, the planning convention would be total events; the outcomes are not time-to-event outcomes, so their planning figures are participants per arm. These illustrations rely on the observed effect, which can be an unstable basis for planning when estimated in a small trial. A design based on an effect smaller than the one observed would require a larger target. The registry record does not report the assumptions or calculations used to plan the original enrollment of 66.

13. 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 = -1.000; pooled standard deviation σ = 0.806.
2. n = 2 × (1.96 + 0.842)² × 0.806² / -1.000² = 10.2, rounded up to 11 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 <- -1                      # observed difference in means
sigma <- 0.806225774829855                     # 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(5772156)
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 = 11 (80% power), 14 (90% power)
 75% of observed effect: n per arm = 19 (80% power), 25 (90% power)
 50% of observed effect: n per arm = 41 (80% power), 55 (90% power)
power.t.test: 11.2 
Simulated power at n = 11 per arm: 0.787 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and 19 outcome measures, with 18 secondary outcomes posted. Multiple outcomes create a multiplicity issue: if each is tested separately, some results may appear statistically persuasive by chance even when there is no corresponding underlying difference. In general, a prespecified testing hierarchy or an adjustment for multiple testing can help control this concern. The registry record does not report a multiplicity strategy, a hierarchy among secondary endpoints, or a detailed statistical analysis plan.

The primary comparison has an unadjusted p-value of < 0.001. The secondary comparisons shown also have unadjusted p-values. Their interpretation should therefore account for the possibility of multiple testing rather than treating each p-value as an isolated confirmatory result. The record lists zero analysis entries and the displayed secondary outcomes have no reported analysis entries. This does not establish what analyses may have been conducted outside the registry; it means that a full account of those analyses is not reported in the registry record.

Missing-data handling is not reported in the registry record. The record does not state how many participants had a missing primary hemoglobin measurement, whether any outcomes were unavailable, or how missing observations were handled. It also does not identify the analysis population—for example, whether the posted comparison includes everyone randomized, only participants with observed outcomes, or another defined group. These details matter because excluding participants or measurements can affect the balance created by randomization.

The record does not report interim analyses, stopping rules, protocol deviations, or whether analyses were adjusted for baseline variables. The original sample-size justification and detailed prespecified analysis methods are also not reported in the registry record. These omissions do not prove that such procedures were absent; they limit what can be verified from the posted information. Readers should distinguish between what the registry reports and what may have been specified or done elsewhere.

As a result, the primary estimate can be described from the posted group summaries, but a full appraisal of risk of bias and confirmatory status requires details that are not reported in the registry record. The distinction is especially important for secondary outcomes, where multiplicity, outcome definitions, and analysis populations could alter how much weight the apparent pattern deserves.

15. 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 adverse-event summary lists 33 participants at risk for serious adverse events in each group and reports zero serious adverse events in both groups. It also lists 33 participants at risk for other adverse events in each group and reports zero other adverse events in both groups. The record reports zero deaths in each group and lists no serious adverse-event terms.

These figures describe what is recorded in the registry; they do not establish that no adverse events of any kind occurred outside the reported categories or observation period. The registry record does not report detailed event definitions, the period of safety follow-up, collection methods, or how events were assessed. It also does not provide information about whether the listed at-risk counts represent all randomized participants or a safety population defined separately.

Zero recorded events in a group should not be read as proof that the risk is zero. With limited numbers of participants, uncommon events may not appear in the observed record. The safety summary is therefore a description of the posted counts, not a complete characterization of safety or a basis for comparing risks beyond these recorded data.

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

The result shows that, among the participants included in the posted primary outcome summaries, the mean hemoglobin change was 1.1 g/dL in the prophylactic methylergonovine group and 2.1 g/dL in the placebo group. The reported mean difference is -1.0 g/dL, with a confidence interval from -1.389 to -0.611 and an unadjusted p-value of < 0.001. This is evidence of a group difference in the measured endpoint in this trial, subject to the assumptions and reporting limitations.

It does not show that every participant had the same response, nor does it directly quantify blood loss. The primary outcome is a change in hemoglobin; the registry’s study summary describes the broader interest as blood loss in scheduled twin cesarean deliveries. The secondary outcomes provide related but distinct information. They do not remove uncertainty about the primary endpoint or establish that every clinically relevant measure changed in the same way.

The result also does not establish the mechanism behind the observed group difference, how it would generalize to other patient populations or settings, or whether the same estimate would be obtained in another study. Enrollment was 66, with 33 participants in each group in the posted primary results. In a trial of this size, estimates can remain sensitive to individual observations, especially for less common outcomes. Important details such as eligibility criteria, missing-data handling, analysis population, and the original statistical plan are not reported in the registry record.

Statistical evidence and clinical meaning are related but not identical. The p-value does not tell readers whether a difference is important to patients or clinicians, and the confidence interval does not supply a threshold for importance. The registry record does not report a threshold for a clinically important hemoglobin change. The finding should therefore be understood as an estimated difference in the posted measurement, not as a stand-alone judgment about treatment decisions.

The secondary findings and safety counts also need context. Secondary comparisons are unadjusted, the registry does not report a multiplicity plan, and zero recorded adverse events do not prove that the risk of an event is zero. The data support a careful description of this trial’s results, but the record alone cannot answer all questions about robustness, safety, or applicability.

17. Why This Trial Matters Statistically

This trial is statistically interesting because it places a randomized comparison in a specific setting identified by the registry: cesarean delivery with twin gestations. The study summary notes that these pregnancies are at higher risk of postpartum hemorrhage, while the primary outcome is a measurable change in maternal hemoglobin. The design compares prophylactic methylergonovine with matching placebo rather than relying on a comparison between patients who received different care by choice. That randomized structure is relevant to interpreting group differences, while the small enrollment means uncertainty and balance still require attention.

The posted primary estimate is accompanied by a confidence interval and a p-value, allowing readers to examine both the direction and precision of the group contrast. The secondary outcomes extend the picture to recorded hemorrhage and additional treatment measures. Looking across distinct endpoints can be informative, but the unadjusted secondary results and absent multiplicity plan make it important not to treat every apparent difference as a separate confirmation.

The record also illustrates why registry transparency matters. Design details such as the original sample-size rationale, statistical analysis plan, analysis population, missing-data handling, and interim analyses are not reported in the registry record. Without them, readers cannot fully assess whether the posted analyses match the intended procedures. The planning illustrations on this page are useful for understanding how assumptions about effect size and power relate to enrollment, but they are not a reconstruction of the original trial design.

Finally, the endpoint distinction matters: hemoglobin change is related to bleeding but is not itself a direct blood-loss measure. A statistically clear difference in this endpoint does not automatically settle interpretation of other outcomes. The value of the trial’s report is in its defined randomized comparison and the estimates it makes available, read together with their precision and the limits of the registry record.

18. 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 posted primary outcome includes 33 participants per group, and the overall enrollment is 66. This is a limited base for estimating group differences and especially for describing less common events. The registry record does not report participant characteristics in the material, so it is not possible to assess how closely the study population resembles other groups of patients undergoing cesarean delivery with twin gestations.

The registry’s summary describes scheduled twin pregnancy cesarean deliveries, but detailed eligibility criteria and the handling of exclusions are not reported in the registry record. Nor does the record state whether all randomized participants contributed to each outcome. Missing measurements, protocol deviations, withdrawals, and the analysis population are not described. These omissions make it harder to judge whether the posted groups preserve the benefits of randomization through analysis.

The primary outcome is hemoglobin change rather than a direct measurement of blood loss. Although the registry lists estimated and quantitative blood loss among its secondary outcome categories, the measurement procedures and definitions are not reported. The primary timeframe is described as baseline and postoperative day one, approximately 48 hours, but further detail about sample collection and the exact timing of measurements is not reported in the registry record.

The registry classifies the study as double-masked, but it does not identify which parties were masked or describe how masking was maintained. It does not report the method used to generate the random sequence or how allocation was concealed. These details are relevant to evaluating potential biases in treatment assignment, care, and outcome assessment.

Finally, the record does not report the original sample-size justification, detailed analysis plan, multiplicity strategy, interim analyses, or missing-data methods. Secondary results are unadjusted and should be interpreted cautiously. The reported absence of adverse events is limited to the counts recorded in the registry, with safety follow-up and event ascertainment details not reported. These reporting gaps do not show that procedures were absent, but they limit independent evaluation of the trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Prophylactic Methylergonovine for Twin Cesarean — NCT05772156.
• Registry record last updated 2025-06-13; status last verified 2025-05.
• Results first posted 2025-06-13.
• 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.

22. Record Summary

The registry record describes NCT05772156, titled “Prophylactic Methylergonovine for Twin Cesarean,” as a completed Phase 4 randomized, double-masked, parallel-group trial sponsored by Columbia University. Enrollment is listed as 66. The study start date is 2023-03-07, and the primary completion date is 2024-03-03.

The primary outcome is change in maternal hemoglobin level from baseline to postoperative day one, approximately 48 hours. The posted means are 1.1 g/dL for prophylactic methylergonovine and 2.1 g/dL for placebo; the reported mean difference is -1.0 g/dL, with a confidence interval from -1.389 to -0.611 and p < 0.001. Selected secondary results and adverse-event counts are summarized elsewhere on this page.

The registry does not report the original sample-size rationale, detailed statistical plan, analysis population, or missing-data procedures. Those omissions limit how completely the posted estimates can be assessed.