Carbetocin on Myocardial Repolarization Dynamics in Obstetrics Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Carbetocin on Myocardial Repolarization Dynamics in Obstetrics Study (NCT03716076), a randomized phase 4 study. The primary outcome is Tp-e.

2. Clinical Question

The registry describes the study purpose as examining the relationship between carbetocin dose and transmural dispersion of repolarization, or TDR. Tp-e is the registered primary measure, expressed in milliseconds. The comparison is between two active doses, not between carbetocin and no treatment or placebo. The statistical contrast therefore concerns the observed mean Tp-e in the 100 mcg group relative to the 50 mcg group at the specified measurement time.

The posted outcome summaries give a mean Tp-e of 69.5 milliseconds for the 50 mcg group and 74.7 milliseconds for the 100 mcg group. The recalculated unadjusted mean difference is 5.2 milliseconds, with a confidence interval from 1.35 to 9.05 and an unadjusted p-value of 0.008. These figures describe the registered comparison; they do not establish what the difference means clinically or how it relates to arrhythmia risk. A threshold for a clinically important difference is not reported in the registry record.

The study concerns a specific obstetric setting and a measurement taken shortly after dosing. Its results should be read as evidence about this endpoint, timing, and comparison, rather than as an answer to broader questions about other patients, treatment settings, or outcomes.

3. Trial Design

The Carbetocin on Myocardial Repolarization Dynamics in Obstetrics Study is registered as NCT03716076. It is a phase 4 study with randomized allocation, double masking, and a parallel design. The sponsor is the University of British Columbia. The registry lists enrollment of 50 and a completed status. The recorded study start is 2018-11-01, and primary completion is recorded as 2019-06-15.

The trial enrolled healthy parturients scheduled for elective cesarean delivery under spinal anesthesia, according to the official title. Participants were assigned to receive carbetocin post-delivery at either 50 mcg or 100 mcg. The primary comparison uses the 50 mcg group as the control and the 100 mcg group as the other arm. The outcome summaries report 22 participants in the 50 mcg arm and 19 in the 100 mcg arm for the primary endpoint. The registry record does not explain the relationship between those endpoint counts and the listed enrollment.

Randomization is intended, in general, to reduce systematic differences between comparison groups at the point of assignment. Double masking indicates that the registry classifies the study as masked at two levels, but the identities of the masked parties and the practical masking procedures are not reported in the registry record. The record also does not describe the randomization sequence, allocation concealment, or whether assignment used any stratification.

The registered primary endpoint is mean Tp-e, measured 5 minutes after carbetocin administration. The primary endpoint description defines Tp-e as the time interval between the peak and end of the T-wave. Other outcomes include arrhythmia and several QTc and Tp-e measurements at specified times. The registry record does not report a full protocol, eligibility criteria beyond the information in the title, or detailed follow-up procedures. Although the study is completed, the posted statistical analysis details are limited.

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 Tp-e, measured over 5 minutes post-carbetocin administration.

The primary endpoint is Tp-e, measured in milliseconds 5 minutes after carbetocin administration. The registry defines it as the time interval between the peak and the end of the T-wave. The endpoint is continuous, and the posted group summaries are means with standard deviations. The primary comparison is therefore a difference in average Tp-e between the 50 mcg and 100 mcg post-delivery carbetocin groups.

The study description places this measure in the context of transmural dispersion of repolarization, abbreviated TDR. In general, an electrocardiographic interval can be used as a measurable physiological marker when researchers want to compare how a biological process varies across treatment groups. Tp-e was selected as the primary measure for this study's question about carbetocin dose and myocardial repolarization dynamics. The registry record does not provide a detailed rationale for choosing this endpoint over other measures or establish a threshold that would define a clinically meaningful difference.

A continuous measure retains information about the size and direction of individual values, rather than reducing the outcome to a yes-or-no event. A group mean gives a compact description of the central level, while the standard deviation describes how spread out the recorded values are within that group. Neither the mean nor the standard deviation alone describes every participant's measurement. The posted primary summary does not include endpoint-specific ranges or individual-level data.

The endpoint is measured at a particular time after dosing, so the result pertains to that time point. It is not by itself a measure of arrhythmia occurrence, nor does the registry report that Tp-e is a direct clinical outcome in this study. The relationship between this physiological measure and any clinical consequences is not reported in the registry record.

7. Results Posted in the Registry

• Participant Receives 100 mcg of Carbetocin Post-delivery.: mean 74.70 versus 69.50 on control; difference 5.20 (95% CI 1.35 to 9.05), standardized effect d = 0.80; z-test p = 0.008.

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.

QTc at 5 Min

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Participant Receives 100 mcg of Carbetocin Post-delivery.: mean 434.20 versus 435.10 on control; difference -0.90 (95% CI -12.30 to 10.50), standardized effect d = -0.05; z-test p = 0.877.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Participant Receives 100 mcg of Carbetocin Post-delivery. and the control. The interval gives the range of effects that remain compatible with the data.

QTc 10 Min

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Participant Receives 100 mcg of Carbetocin Post-delivery.: mean 431.90 versus 431.60 on control; difference 0.30 (95% CI -9.99 to 10.59), standardized effect d = 0.02; z-test p = 0.954.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Participant Receives 100 mcg of Carbetocin Post-delivery. and the control. The interval gives the range of effects that remain compatible with the data.

QTc 5 Min Spinal

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Participant Receives 100 mcg of Carbetocin Post-delivery.: mean 413.60 versus 409.40 on control; difference 4.20 (95% CI -7.01 to 15.41), standardized effect d = 0.23; z-test p = 0.463.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Participant Receives 100 mcg of Carbetocin Post-delivery. and the control. The interval gives the range of effects that remain compatible with the data.

The registered secondary outcomes cover arrhythmia and electrocardiographic measures, including QTc at multiple times and Tp-e at additional times. The posted continuous summaries for QTc at 5 minutes, QTc at 10 minutes, and QTc 5 minutes after spinal anesthesia show small estimated mean differences relative to the primary comparison, with confidence intervals that include zero. These outcomes use different timing or measures, so they provide related but not interchangeable information about the study's question.

As a broad pattern, the secondary continuous summaries do not show the same clear separation between dose-group means as the primary Tp-e comparison. This means that the primary finding should be understood as specific to the registered primary measurement and time, rather than as a uniform pattern across all recorded electrocardiographic outcomes. The secondary outcomes may help describe whether measurements at other times or of other features follow a similar pattern, but they do not independently confirm the primary result.

There are six secondary outcomes listed in the registry, while detailed posted summaries are available for only some of them. Outcome-specific inferential results for the other registered outcomes are not reported in the registry record. Their absence should not be interpreted as evidence of no difference; it means the available record does not give enough information to characterize those comparisons.

Unadjusted secondary results carry less weight when many outcomes and measurement times are considered. In general, multiple testing raises the chance that at least one result will appear statistically notable even if no corresponding effect exists. The registry record does not report whether the secondary analyses were adjusted for multiplicity, designated as exploratory, or arranged in a prespecified testing hierarchy. The displayed secondary comparisons should therefore be treated as descriptive or exploratory evidence unless a fuller analysis plan says otherwise.

Secondary outcomes also differ in clinical meaning and measurement properties. A continuous QTc or Tp-e measure is not the same as an arrhythmia event, and a result at one time point does not establish a pattern over time. The registry record does not report the analysis details needed to combine these measures into a single conclusion. The primary endpoint remains the main registered basis for the dose comparison, with secondary results offering context rather than a separate definitive answer.

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

• Arrhythmia
• QTc at 5 Min
• QTc 10 Min
• QTc 5 Min Spinal
• Tp-e 5 Min Post-spinal
• Tp-e at 10 Min

9. Statistical Interpretation

10. Statistical Methods Explained

The registry classifies the primary endpoint as a continuous measure summarized by a mean and standard deviation. For each dose group, the mean is the arithmetic average of the recorded Tp-e values included in that summary. The standard deviation describes how much those measurements vary around their group mean. It is not the uncertainty of the mean itself; uncertainty in a mean also depends on the number of observations and the analysis assumptions.

What does the mean difference describe?

The displayed comparison is an unadjusted mean difference: the 100 mcg group's mean minus the 50 mcg group's mean. The estimate is 5.2 milliseconds. A positive value means the posted mean is higher in the 100 mcg group for this outcome and time point. This is a difference between group averages, not a statement that every participant in one group had a higher value than every participant in the other group. It also is not an adjusted estimate unless adjustment is explicitly described; the registry record does not report an adjusted primary analysis.

In general, an unadjusted comparison uses the group summaries without accounting for covariates or other features of the trial design beyond what is reflected in those summaries. Random assignment supports a comparison of assigned groups, but it does not itself document which analysis population was used or how missing values were treated. The registry record does not report those details. The displayed recalculation should therefore be understood as a simple summary-statistic comparison, not as confirmation of the exact analysis conducted by the sponsor.

How should the confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimate. Its lower and upper limits mark values that are compatible with the data under the calculation's assumptions and interval procedure. For this primary comparison, the posted recalculated interval runs from 1.35 to 9.05 milliseconds. It describes uncertainty in the estimated mean difference; it does not give the range of individual Tp-e measurements, and it does not guarantee that the true difference lies within these particular limits.

The confidence level and specific interval procedure are not reported in the registry record. No particular test or model is named in the reported analysis entry. The p-value and interval displayed with the recalculation should consequently be read as unadjusted summary-statistic results, not as a fully documented sponsor analysis. The calculated comparison is not flagged as discrepant from a sponsor result, but the sponsor's numerical result and method are not available in the analysis entry.

What does the p-value contribute?

In general, a p-value measures the compatibility of the observed data with a specified null hypothesis, conditional on the model and assumptions used to calculate it. The primary comparison's unadjusted p-value is 0.008. This value is not the probability that the observed effect is due to chance, and it does not measure the probability that one dose is better or worse. It also cannot determine whether a difference is clinically important. That judgment needs clinical context and a meaningful threshold, which are not reported in the registry record.

A p-value depends on both the estimated effect and the precision of the estimate. A small p-value does not by itself show that the estimate is precise enough for every decision, while a larger p-value does not demonstrate that groups are equivalent. Equivalence or non-inferiority requires an appropriate question, margin, and analysis plan; none is reported in the registry record.

Why does variability matter?

General statistical explanation: variability affects how precisely a group mean and a difference between group means can be estimated. Greater variation among participants tends to make a group mean less precise if other features are unchanged. When outcomes are counts or rates, over-dispersion means that observed variability exceeds what a simple model assumes; accounting for it can widen uncertainty and change inference. The primary outcome is continuous rather than a count, and the registry record does not report an over-dispersion model or a need for one.

For Tp-e, the posted standard deviations are 7.7 milliseconds and 4.7 milliseconds in the two arms. They are descriptive statistics. They do not establish that the data are normally distributed, that observations are independent, or that there are no outliers. Individual observations, distribution plots, and diagnostic checks are not reported in the registry record. General methods for comparing means often rely on assumptions about independent observations and the behavior of sampling distributions; which assumptions and checks were used for the sponsor analysis is not reported in the registry record.

The arm summaries list endpoint sample sizes of 22 and 19. The registry record does not explain missing outcome data, exclusions after randomization, or whether these are all randomized participants with available primary measurements. The enrollment figure is 50, but it should not be assumed that every enrolled participant contributed to every endpoint summary. In general, missingness can affect precision and can also introduce bias if the likelihood of an observed measurement is related to participant characteristics or outcomes. The missing-data process and any method for addressing it are not reported in the registry record.

The design is described as randomized, double-masked, and parallel. In general, randomization helps balance prognostic characteristics on average across groups, while masking may reduce some behavior or measurement differences. Those design labels do not replace reporting of allocation procedures, masking details, adherence, and analysis populations. The record does not state whether the primary analysis followed assigned treatment regardless of actual receipt, nor does it describe a per-protocol analysis.

There are multiple registered outcomes and repeated measurement times. In general, examining many outcomes or time points increases the chance that at least one unadjusted result appears notable by chance. The registry record does not report a multiplicity strategy, a hierarchy of secondary hypotheses, or an adjustment across endpoints. The primary endpoint is identified, but the exact pre-specified testing sequence and any interim-analysis plan are not reported in the registry record. These omissions matter when interpreting secondary comparisons, not because they invalidate the descriptive values, but because they leave the wider inferential context uncertain.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 5.2 milliseconds, with a confidence interval from 1.35 to 9.05 milliseconds. The interval describes uncertainty around the difference in group means, not variation among individual measurements. Its width reflects the amount of information in the observed summaries together with the interval calculation's assumptions. The confidence level and the procedure used to form this interval are not reported in the registry record.

The interval's lower and upper limits are both on the positive side of zero. In the context of the stated contrast, that is consistent with a higher mean in the 100 mcg group. The limits also indicate that the data are compatible with a range of positive differences, rather than identifying one exact value. The point estimate is the center of the reported comparison, but it should not be treated as known without uncertainty.

For a continuous endpoint, precision is affected by the observed variability and the amount of endpoint information. The group summaries report standard deviations of 7.7 milliseconds and 4.7 milliseconds, with endpoint counts of 22 and 19. These summaries allow a simple unadjusted recalculation, but they do not substitute for individual-level data or full analysis documentation. The registry record does not provide missing-data details, diagnostic checks, or a sponsor-reported interval for the primary comparison.

Statistical precision is different from clinical importance. The registry record does not define a threshold for a meaningful Tp-e difference, so the interval cannot by itself establish whether the range matters clinically. Nor does it speak directly to arrhythmia events or other outcomes. Its scope is the mean Tp-e difference at the specified measurement time between the registered dose groups.

The p-value of 0.008 is another way of expressing evidence relative to a null comparison under calculation assumptions; it is not a measure of interval precision or effect importance. Both the estimate and its interval are needed for a fuller account of the numerical result. They remain unadjusted recalculations from posted group summaries because the registry's analysis entry does not report the sponsor's numerical estimate or method.

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 planning figures are illustrations based on the observed mean difference, not the trial's original design justification. For this continuous outcome, they are expressed as participants per arm, not as total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses a stated fraction of the observed effect as the effect to detect: the full observed effect, 75% of it, or 50% of it.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect and the assumptions were correct. The 90% power column uses a higher target chance of detection, so it requires more participants per arm for the same effect scenario. Power is a property of a planned design under stated assumptions; it is not a guarantee of a statistically significant result.

The displayed planning scenarios show the general relationship between effect size and sample size: planning to detect a smaller effect requires more participants. The observed difference is used as the reference for those scenarios, but the observed estimate is uncertain and may not equal the effect that would be found in another study. The planning figures do not account for information that is not specified in the assumptions, such as missing measurements or departures from the model.

The registry record does not report the trial's own sample-size justification or the assumptions used when its original design was planned. The listed enrollment and the endpoint counts are actual registry entries, whereas the planning figures are hypothetical design illustrations. These planning calculations are not observed power; they do not describe the probability that the completed trial's result was correct or the probability that a treatment effect exists.

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 = 5.200; pooled standard deviation σ = 6.490.
2. n = 2 × (1.96 + 0.842)² × 6.490² / 5.200² = 24.5, rounded up to 25 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 <- 5.2                      # observed difference in means
sigma <- 6.49005155840608                     # 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(3716076)
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 = 25 (80% power), 33 (90% power)
 75% of observed effect: n per arm = 44 (80% power), 59 (90% power)
 50% of observed effect: n per arm = 98 (80% power), 131 (90% power)
power.t.test: 25.4 
Simulated power at n = 25 per arm: 0.796 (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 lists a primary endpoint alongside multiple secondary outcomes and measurement times. When several statistical comparisons are conducted, the chance of obtaining at least one nominally notable result can increase. General approaches to this issue include prespecifying a primary hypothesis, controlling the family-wise error rate, controlling the false discovery rate, or treating secondary analyses as exploratory. Which approach, if any, was used is not reported in the registry record. The record does not describe an adjustment across the primary and secondary comparisons or a hierarchy governing their interpretation.

The primary outcome is identified as Tp-e at 5 minutes after carbetocin administration, but the registry's reported-analysis entry does not give a method, estimate, interval, or p-value. The recalculated p-value is unadjusted. It should not be read as accounting for other outcomes, time points, or any multiplicity plan. Whether a pre-specified statistical analysis plan included procedures not represented in the registry is not reported in the registry record.

The record does not report an interim-analysis plan, early stopping rules, or repeated-look adjustments. It would therefore be inappropriate to assume that interim analyses occurred or did not occur. The same applies to the planned sample-size rationale: the registry record does not report the original calculation or its effect-size assumptions. The posted planning illustration is based on the observed effect and is not a replacement for the trial's original design documentation.

Endpoint summaries give group counts, but the record does not describe missing data, reasons for missingness, exclusions, or how incomplete records were handled. It also does not state the primary analysis population, such as whether all randomized participants were analyzed in their assigned groups. These details matter because missingness and exclusions can affect both precision and comparability. The enrollment entry should not be treated as proof that every enrolled participant contributed data to every outcome.

The adverse-event record lists 25 participants at risk in each arm, while the primary endpoint summaries list different arm-specific counts. The registry does not explain the relationship between these outcome-specific counts and the safety denominators. They should be read as separate entries for separate reporting purposes rather than assumed to represent the same analysis population. The record does not report a reconciliation or a detailed participant flow account.

These omissions do not change the arithmetic of the posted descriptive summaries, but they limit assessment of how the sponsor's planned methods were implemented. A fuller protocol and analysis plan would be needed to evaluate endpoint hierarchy, handling of missing data, analysis populations, interim monitoring, and multiplicity procedures.

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 record reports zero serious adverse events among 25 participants at risk in the 50 mcg group and zero among 25 participants at risk in the 100 mcg group. It also reports zero other adverse events in each arm and zero deaths in each arm. These are the registry's posted safety counts for the categories recorded.

Zero reported events in these entries means that no events were counted in the stated categories and denominators in the registry record. It does not establish that an event is impossible, nor does it show that the groups have identical safety profiles. With no reported events, a comparative event-rate estimate cannot be read from these counts. The registry record does not list serious adverse-event terms.

The safety denominators differ from the primary endpoint counts, and the record does not explain how the safety population was defined or why those counts differ. The safety entries should not be treated as if they necessarily describe the same set of participants as the primary outcome summaries. Timing, surveillance procedures, and event ascertainment details are not reported in the registry record.

These figures are a concise account of the adverse-event information posted, not a complete assessment of safety. No clinical conclusion should be drawn from the absence of recorded events alone.

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

The posted primary summaries indicate a higher mean Tp-e in the 100 mcg arm than in the 50 mcg arm 5 minutes after administration. The recalculated unadjusted mean difference is 5.2 milliseconds, with an interval from 1.35 to 9.05 and an unadjusted p-value of 0.008. This describes the observed group comparison in the registry record, alongside uncertainty around the estimated mean difference.

The finding does not by itself establish that the difference is clinically important. The record does not provide a threshold for interpreting a difference in Tp-e or explain how this measurement should translate into a clinical outcome. The endpoint is a physiological measurement, not an arrhythmia event. Although arrhythmia is listed as a secondary outcome, inferential details for that outcome are not reported in the registry record.

The comparison also does not establish the effect of carbetocin versus no carbetocin. Both groups received carbetocin; the contrast is between the 50 mcg and 100 mcg post-delivery doses. It does not establish effects at other doses, times, or in other patient populations. The trial's stated setting is healthy parturients scheduled for elective cesarean delivery under spinal anesthesia.

Randomization and double masking are design features recorded by the registry, but full information about implementation, analysis populations, missing data, and the analysis plan is absent. The displayed comparison is a recalculation from summary statistics and is unadjusted. It is not a substitute for a complete sponsor analysis or participant-level evaluation.

Likewise, a p-value does not state the probability that a hypothesis is true, and a confidence interval does not show the range of values for individual participants. The interval and p-value answer different statistical questions from whether a result is clinically important or whether the groups can be considered equivalent. The registry record does not report an equivalence margin, non-inferiority margin, or a threshold for meaningful change.

The safety entries list no serious or other adverse events and no deaths in either arm, using their reported denominators. Those counts are limited to the registry's recorded categories and do not prove an absence of all possible harms. Overall, the posted information supports a focused statistical description of this dose comparison and its primary measurement, while leaving broader clinical interpretation and several analysis details unresolved.

17. Why This Trial Matters Statistically

This study illustrates why outcome definition and measurement timing are central to interpreting a clinical trial. The primary question is not a broad assessment of every possible effect of carbetocin. It is a comparison of mean Tp-e between two post-delivery doses at a specified time in a defined obstetric setting. Keeping that scope explicit prevents a numerical result from being generalized to other outcomes or populations without evidence.

It also demonstrates the distinction between a group-level estimate and its uncertainty. The mean difference gives the direction and size of the observed contrast, while the confidence interval communicates uncertainty in that estimate. The unadjusted p-value adds information about compatibility with a zero-difference null model, but it does not replace the estimate or determine clinical relevance. A meaningful interpretation needs the endpoint's clinical context, which the registry does not supply as a threshold.

The comparison is an example of a recalculation from posted group summaries when the registry's own analysis entry does not report its inferential details. Such recalculation can help readers understand the scale and precision of a simple unadjusted contrast. It cannot recover undocumented choices about model form, missing data, analysis population, or multiplicity. Statistical transparency depends not only on a numerical result but also on clear reporting of these choices.

Multiple secondary outcomes make careful interpretation especially important. Related electrocardiographic measurements can provide context, but they do not automatically form a single coherent test, and unadjusted comparisons may be difficult to interpret when many hypotheses are considered. The registry record does not state the multiplicity strategy, so secondary findings deserve cautious weight.

Finally, the safety entries show how denominators and outcome-specific populations can differ in registry records. Clear participant flow and analysis-population reporting are necessary for readers to understand which observations inform each result. These considerations apply broadly to clinical trial reporting and are particularly relevant when sample sizes are modest and outcomes are measured at multiple times.

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 registry record leaves important details about the trial conduct and analysis unreported. It identifies randomization, double masking, and a parallel design, but does not describe the randomization procedure, allocation concealment, who was masked, or how masking was maintained. The record also does not provide a protocol or a detailed statistical analysis plan, so the prespecified analysis choices cannot be checked against the posted summaries.

The primary statistical analysis entry contains no method or inferential result. The available mean difference, interval, and p-value are recalculated from posted summary statistics and are unadjusted. They do not show whether the sponsor used a different model, adjusted for other variables, or conducted additional analyses. The discrepancy flag is false, but this does not supply the missing analysis documentation.

Endpoint counts are 22 in one primary arm and 19 in the other, while the listed enrollment is 50. The safety entries use 25 at-risk participants in each arm. The registry record does not explain participant flow or reconcile these outcome-specific counts. Missing-data reasons, exclusions, adherence, and analysis-population definitions are also not reported. Consequently, the relationship between enrollment and each analysis set cannot be assessed from this record alone.

The registry lists six secondary outcomes, but detailed summaries are posted for only some of them. It does not state how multiplicity was addressed, whether secondary analyses were exploratory, or whether any outcome hierarchy was specified. It also does not report interim analyses or the original sample-size assumptions. The planning illustration based on the observed effect cannot establish the study's original design rationale.

The posted endpoint summaries provide means and standard deviations but not participant-level data, distributional diagnostics, ranges, or a clinically meaningful difference threshold. The study setting is specific, and the record does not establish generalizability to other populations or clinical settings. These limitations constrain both the statistical audit and clinical interpretation without changing the values that are posted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Carbetocin on Myocardial Repolarization Dynamics in Obstetrics Study — NCT03716076.
• Registry record last updated 2021-05-14; status last verified 2021-04.
• Results first posted 2021-05-14.
• 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.

22. Record Summary

NCT03716076 is a completed phase 4, randomized, double-masked, parallel study sponsored by the University of British Columbia. It compared post-delivery carbetocin doses of 50 mcg and 100 mcg in healthy parturients scheduled for elective cesarean delivery under spinal anesthesia. The registry lists enrollment of 50.

The primary endpoint was mean Tp-e in milliseconds at 5 minutes after carbetocin administration. The posted arm means were 69.5 in the 50 mcg group and 74.7 in the 100 mcg group. The recalculated unadjusted mean difference was 5.2, with a confidence interval from 1.35 to 9.05 and an unadjusted p-value of 0.008.

The registry does not report the sponsor's primary analysis method or numerical result in its analysis entry. Details about missing data, analysis populations, multiplicity, and the original sample-size rationale are not reported in the registry record. Safety entries list zero serious adverse events, zero other adverse events, and zero deaths in each arm, using the reported safety denominators.