RCT (Randomized Controlled Trial) of IV Acetaminophen for Post Cesarean Pain Relief: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RCT (Randomized Controlled Trial) of IV Acetaminophen for Post Cesarean Pain Relief (NCT02046382), a randomized phase 4 study. The primary outcome is Total Oxycodone (mg).

2. Clinical Question

The comparison is between assignment to the two scheduled regimens, not between acetaminophen and no postoperative pain management. Both groups were described as receiving a scheduled infusion, and the posted primary outcome concerns rescue oxycodone use. The endpoint therefore addresses one part of the broader clinical question: opioid consumption during the inpatient stay. It is not itself a direct measure of pain intensity, recovery, or satisfaction.

3. Trial Design

The registry describes NCT02046382 as a randomized, triple-masked, parallel-group phase 4 trial of intravenous acetaminophen for post-cesarean pain relief. The record lists an enrollment of 132 and a completed study. The start is recorded as 2014-01 and primary completion as 2016-12. TriHealth Inc. is listed as the sponsor.

Participants were assigned to intravenous acetaminophen or normal saline. The intervention descriptions specify administration every 8 hours for 48 hours, beginning intraoperatively after delivery. The acetaminophen regimen is described as 1000mg in 100mL solution per dose; the saline regimen as 100mL per dose. Each description specifies a total of 6 doses. Randomized allocation and a parallel model mean the comparison is between assigned groups, rather than a within-person crossover. Triple masking indicates the registry's masking classification; the identities of the masked parties are not reported in the registry record.

The primary endpoint is total oxycodone in mg for breakthrough pain during the inpatient stay, with a timeframe of approximately 2 - 7 days. The posted primary results list 57 participants for the intravenous acetaminophen arm and 47 for the normal saline arm. These result counts should not be treated as a reconciliation of the registry's enrollment figure: the reason for the difference is not reported in the registry record.

The registry lists number of participants with narcotic-associated side effects and length of stay as secondary outcomes. It posts results for narcotic-associated side effects, but length-of-stay results are not reported in the registry record. The original sample-size justification, detailed eligibility rules, masking procedures, and planned analysis methods are not reported in the registry record.

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 Total Oxycodone (mg), measured over approximately 2 - 7 days.

The primary endpoint is total oxycodone, measured in mg, used for breakthrough pain during the inpatient stay. The registry gives the timeframe as approximately 2 - 7 days and describes the outcome as a mean with standard deviation. In contrast to a pain score, which records a patient's reported pain intensity at a particular assessment, this endpoint quantifies rescue opioid use over the inpatient period.

It is relevant to the trial's stated question because the registry summary asks whether patients receiving scheduled intravenous acetaminophen use less narcotic pain medication than patients receiving no intravenous acetaminophen. The endpoint is a measure of medication consumption, not a direct measure of pain relief. Oxycodone use can reflect pain, clinician prescribing and administration, patient decisions, and the availability or use of other pain-management options. The registry record does not report enough detail to separate those influences.

A group mean offers a concise description of average use, while the standard deviation describes how much individual observations vary around that average. The endpoint's meaning therefore depends both on the difference in group means and on the spread of observations. It should be interpreted as an inpatient medication-use outcome, not as a complete account of pain, safety, length of stay, or longer-term recovery.

7. Results Posted in the Registry

• Normal Saline: mean 65.00 versus 47.00 on control; difference 18.00 (95% CI 1.34 to 34.66), standardized effect d = 0.42; z-test p = 0.034.

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 Narcotic Associated Side Effects

• 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:
  • Normal Saline: 19.1% (9/47) versus 29.8% (17/57) on control; risk difference -10.7 percentage points (95% CI -27.0 to 5.7), risk ratio 0.64 (0.32–1.31); unadjusted two-proportion z-test p = 0.211.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Normal Saline and the control. The interval gives the range of effects that remain compatible with the data.

The registry identifies narcotic-associated side effects and length of stay as secondary outcomes. Posted numerical results are available for narcotic-associated side effects, but length-of-stay results are not reported in the registry record. The broader study summary mentions self-reported pain scores, but pain-score results are also not reported in the registry record. Accordingly, the secondary evidence is incomplete relative to the range of outcomes described in the record.

The available secondary comparison does not provide a clear, precise complement to the primary oxycodone result. Its estimate is uncertain, and its confidence interval spans values on both sides of no difference. That pattern does not establish a secondary outcome difference or rule one out. It also does not resolve whether the primary group-average difference in opioid use corresponded to a difference in self-reported pain, length of stay, or other aspects of recovery.

Secondary outcomes can add context by showing whether a primary result is accompanied by changes in other relevant measures. Their interpretation depends on the number of outcomes examined, the prespecified hierarchy, and the analyses chosen. The registry does not report a multiplicity plan or a detailed statistical analysis plan. When multiple outcomes are tested, unadjusted results can be more likely to include a nominally notable finding by chance. For that reason, unadjusted secondary results generally carry less confirmatory weight than a clearly prespecified primary analysis.

These outcomes should be considered as complementary but not interchangeable. Oxycodone use reflects medication consumption; narcotic-associated side effects address a different aspect of treatment experience; length of stay concerns hospital duration. Missing results for some listed outcomes prevent a comprehensive account of the trial's intended outcome pattern. The posted secondary information can inform the statistical context, but it cannot by itself confirm or negate the primary comparison.

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

• Number of Participants With Narcotic Associated Side Effects
• Length of Stay

9. Statistical Interpretation

10. Statistical Methods Explained

The trial is described as randomized, triple-masked, and parallel-group. Randomization is intended to make assigned groups comparable on average, including with respect to factors that may not have been measured. It does not guarantee that all characteristics will be balanced in a particular trial. Masking is intended to reduce the influence of knowledge of assignment on care or assessment, but the registry does not identify which parties were masked or give procedural details. The parallel model means each participant is assigned to one regimen for the group comparison.

What does a mean difference describe?

A mean summarizes the average value of a continuous outcome. For this endpoint, the outcome is total oxycodone in mg during the inpatient stay. The reported means are 47.0 mg for intravenous acetaminophen and 65.0 mg for normal saline. The comparison reports a mean difference of 18.0 mg in the direction of normal saline relative to intravenous acetaminophen. This direction is important: a positive difference in that stated order corresponds to a higher reported mean in the saline arm. It is a contrast between group averages, not a statement about every individual participant.

The standard deviation describes dispersion of individual observations around the group mean. The posted standard deviations, 39.1 mg and 46.2 mg, indicate that observations vary within both arms. A standard deviation is not the uncertainty interval for the mean difference. It describes variability among observations; the confidence interval describes uncertainty around the estimated contrast. These answer different questions and should not be used interchangeably.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the data and the statistical procedure used to estimate the contrast. For the primary comparison, the reported interval extends from 1.342 to 34.66 mg. It helps show the precision and direction of the estimate: the range is entirely on the positive side of zero for the stated saline-relative-to-acetaminophen contrast, while also allowing a range of possible magnitudes. It is not a range containing a specified proportion of individual participants' oxycodone use, and it is not a guarantee that the true effect lies within the interval.

The registry does not report the method used to construct this interval, whether the primary analysis adjusted for other variables, or details of any distributional checks. It is therefore appropriate to describe the reported interval without attributing a particular model or procedure to it. In general, a confidence interval for a difference is affected by the amount of observed variability and the amount of information in each group. Greater variability or less information tends to produce less precise estimates.

How should the p value be understood?

The primary comparison has an unadjusted p value of 0.034. In general, a p value measures how unusual results at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null model is correct, and it does not measure the size or importance of an effect. Here, “unadjusted” means the posted value is not presented as adjusted for multiple comparisons. The registry does not report the planned multiplicity strategy or the full analysis procedure, so the p value should not be read as resolving those questions.

The registry lists 4 outcome measures and 0 reported analyses. Those record-level counts do not explain the analysis plan or show that no analyses were carried out; they indicate that analysis details are not posted as reported analyses in the record. The endpoint summaries and comparison are available, but the statistical method, analysis population, and handling of missing outcome values are not reported in the registry record.

Why can group variability matter?

General statistical explanation: when a continuous outcome has a broad distribution, a group mean can conceal considerable overlap among individuals. In planning a study, greater variability makes it harder to distinguish a given difference in means from random variation. Some outcomes may also have skewed distributions or unusually large values; the registry does not report distributional information for oxycodone use, so no particular shape should be assumed. If a continuous outcome is strongly skewed, methods that rely on a normal approximation may not describe it well. The record does not say whether this was assessed or addressed.

The planning illustrations explicitly use a normal approximation, equal allocation, and a two-sided significance level of 0.05. These are assumptions for those planning calculations, not evidence about the original trial design. In general, a normal approximation is a simplifying way to estimate how much information may be needed for a comparison. If the true distribution differs substantially from assumptions, actual operating characteristics may differ from the illustration.

Randomized assignment supports a between-group comparison, but interpretation also depends on following the assigned groups, the definition and timing of measurement, and how missing information is handled. The registry identifies the primary outcome timeframe as approximately 2 - 7 days and describes use during the inpatient stay. It does not state whether the analysis followed intention-to-treat principles, whether participants were excluded from the outcome analysis, or how incomplete medication records were treated. Those omissions limit independent assessment of the estimate.

11. Confidence Intervals and Precision

The primary mean difference is 18.0 mg, with a confidence interval from 1.342 to 34.66 mg. The interval is entirely above zero for the stated contrast of normal saline relative to intravenous acetaminophen. It also spans a substantial range of possible difference magnitudes, so the point estimate should not be treated as exact. The posted p value is 0.034 and is unadjusted; it does not replace the interval as a description of precision.

The group standard deviations are 39.1 mg for intravenous acetaminophen and 46.2 mg for normal saline. These describe variation among participants' oxycodone use, not uncertainty in the estimated group means. Both standard deviations are sizable in relation to the reported means, indicating that the group averages do not describe every participant's experience. The confidence interval is the more relevant posted measure for judging uncertainty in the between-arm contrast.

Precision is also influenced by the number of observations contributing to the outcome. The posted endpoint results list 57 participants in the acetaminophen arm and 47 in the saline arm. The registry's overall enrollment is 132, and the record does not explain why the endpoint counts differ from that enrollment figure. It does not report missing-data handling, exclusions, or the analysis population, so the degree to which these counts reflect all randomized participants cannot be determined from the record.

For the secondary side-effect comparison, the risk-difference interval runs from -0.270 to 0.057, spanning zero. That interval is also wide, which leaves uncertainty about the direction and size of the difference. The primary and secondary intervals address distinct outcomes and should not be conflated. More broadly, confidence intervals communicate uncertainty under the methods used; they do not capture every source of uncertainty, such as outcome measurement, incomplete reporting, or differences between the study setting and other settings.

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 participants per arm for 80% power and participants per arm for 90% power. They are not total-event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each row, the effect to detect is the stated fraction of the observed effect. The record does not report the trial's original sample-size justification or design assumptions.

In general, power is the chance that a planned analysis will detect an effect of a specified size under the assumptions used for planning. The 80% power column gives the number of participants per arm calculated for an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the number per arm calculated for a 90% chance. These are planning targets, not guarantees about the outcome of a future or completed study. They are not observed power.

The rows use the observed effect, 75% of the observed effect, and 50% of the observed effect as planning scenarios. Smaller effects require more participants to detect, all else held constant. The displayed figures are illustrations based on those assumptions, rather than a reconstruction of the study's original design. They should not be interpreted as evidence that the trial was designed around the observed result, or as a substitute for the unreported original justification. The planning calculations do not account for information absent from the registry, including its original assumptions about outcome variability, loss to follow-up, or analysis methods.

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 = 18.000; pooled standard deviation σ = 42.449.
2. n = 2 × (1.96 + 0.842)² × 42.449² / 18.000² = 87.3, rounded up to 88 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 <- 18                      # observed difference in means
sigma <- 42.449231499545                     # 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(2046382)
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 = 88 (80% power), 117 (90% power)
 75% of observed effect: n per arm = 156 (80% power), 208 (90% power)
 50% of observed effect: n per arm = 350 (80% power), 468 (90% power)
power.t.test: 88.3 
Simulated power at n = 88 per arm: 0.793 (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 record lists multiple outcome measures, including the primary oxycodone endpoint and secondary outcomes. It does not report a strategy for controlling multiplicity, such as a prespecified hierarchy or an adjustment across tests. The primary p value is explicitly unadjusted. This means it should be interpreted as a result for the reported comparison, not as evidence that the family of outcome comparisons was controlled for false-positive findings. The record does not provide enough information to determine how the investigators intended to interpret several outcome tests together.

The registry's analysis count is recorded as 0, and the reported analyses list is empty. Numerical outcome summaries and comparisons are nevertheless posted. The record does not explain this difference or provide a full statistical analysis plan. It does not state which outcomes were designated as primary in the original protocol, whether analyses were prespecified, or whether any outcomes or analyses were added or changed. These details are not reported in the registry record.

Missing-data procedures are also not reported. The available record does not say whether every randomized participant contributed a primary outcome value, how incomplete medication records were handled, or whether any imputation or sensitivity analyses were used. The participant counts attached to the primary outcome differ from the overall enrollment figure, but the reason is not reported in the registry record. The intended analysis population, including whether the analysis followed assigned groups regardless of adherence, is likewise not reported.

These gaps matter because analysis choices can affect both the estimated group difference and its uncertainty. They also make it harder to assess the risk of bias from selective outcome reporting or exclusions. The registry's randomized and masked design is relevant context, but those design labels do not answer questions about outcome availability or analysis decisions. Interpretation should therefore remain anchored to the posted estimates and their reported uncertainty, while recognizing that multiplicity, missing-data handling, and analysis-population details cannot be independently assessed from the registry record.

15. Safety Results

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

Other (non-serious) adverse events

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

The registry's serious adverse event figures report 0 events among 65 participants at risk in the intravenous acetaminophen group and 0 among 67 participants at risk in the normal saline group. The other adverse event figures also report 0 events among 65 participants at risk and 0 among 67 participants at risk, respectively. These are the event counts and at-risk group sizes posted for safety reporting.

Zero reported events in these groups should be read narrowly. They do not establish that no adverse events occurred outside the registry's reporting definitions, observation period, or reporting process, and they do not demonstrate that the regimens have identical safety profiles. The registry does not report the safety observation duration or further details of event ascertainment. The death figures are not reported in the registry record. No serious adverse event terms are listed.

The safety group sizes differ from those listed for the primary endpoint. The record does not explain the relationship between those denominators and the endpoint analysis counts. Safety counts are not a substitute for the primary efficacy outcome, and the available figures alone do not support a broad safety conclusion.

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

The posted primary comparison describes lower average total oxycodone use in the intravenous acetaminophen arm than in the normal saline arm during the inpatient stay. The reported difference is 18.0 mg in the direction of higher use in the saline arm, with a confidence interval from 1.342 to 34.66. This is evidence about the posted group means and their uncertainty for a specific medication-use endpoint.

It does not establish that every participant receiving acetaminophen used less oxycodone, that pain was lower, or that the difference was caused solely by the assigned infusion. The primary endpoint is opioid consumption, not a self-reported pain score. The registry's stated interest in pain scores does not make those results available; pain-score results are not reported in the registry record. The record also does not report length-of-stay results, despite listing length of stay as a secondary outcome.

The comparison does not answer questions about pain or medication use after discharge, longer-term recovery, or other clinical outcomes beyond those reported. The timeframe is approximately 2 - 7 days, and the description focuses on inpatient use. The posted data also do not establish how results would generalize beyond the trial's cesarean-delivery setting or to care practices different from those used in the study.

Statistically, the estimate is not exact. The confidence interval indicates uncertainty about the magnitude of the group difference, and the standard deviations show variation in individual oxycodone use. The unadjusted p value should not be treated as a measure of clinical importance or as a probability that the treatment effect is real. The absence of reported analysis details, missing-data procedures, and multiplicity plans further limits how fully the result can be evaluated.

The appropriate interpretation is therefore specific: the registry reports a difference in mean inpatient oxycodone use between randomized groups, with uncertainty described by the posted interval. This result alone cannot establish an overall effect on pain relief, recovery, safety, or the balance of benefits and harms.

17. Why This Trial Matters Statistically

This trial illustrates why the endpoint chosen for a clinical question matters. The registry summary frames the study around both self-reported pain and narcotic medication use, while the posted primary endpoint is total oxycodone used for breakthrough pain during the inpatient stay. Medication use is a clinically relevant measure, but it is not identical to pain intensity. Separating these concepts helps prevent an outcome about prescribing or consumption from being interpreted as a direct measure of symptom relief.

The record also illustrates the value of reading an estimate together with its uncertainty. A difference in means is a compact summary, but the standard deviations show that individual outcomes vary, and the confidence interval conveys uncertainty in the group contrast. The p value alone cannot communicate the range of plausible effect sizes or the clinical importance of the endpoint.

Randomization and masking are important design features, yet they do not remove the need for transparent reporting of the analysis population, missing-data handling, multiplicity procedures, and planned methods. Those details are not reported in the registry record. This limits independent assessment of how the posted comparison was constructed, despite the availability of group summaries and an unadjusted comparison.

Finally, registry results can be incomplete relative to a trial's stated aims. Here, secondary outcomes include length of stay, while results are posted for narcotic-associated side effects; the other listed outcomes are not all represented by posted results. Statistical interpretation therefore includes both evaluating the estimates that are available and identifying what the record does not establish. This distinction is essential when communicating trial findings without overstating their scope.

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.

Several limitations specific to this record constrain interpretation. The primary endpoint counts listed for the two arms do not match the overall enrollment figure, and the reason for that difference is not reported in the registry record. The record does not explain whether the endpoint counts reflect missing observations, exclusions, or a different analysis population. Without that information, the relationship between enrollment and the primary comparison cannot be fully assessed.

The registry does not report the original sample-size justification, detailed eligibility criteria, or the statistical analysis plan. The planning illustrations are based on stated assumptions and the observed effect; they do not reconstruct the original design. Analysis details such as adjustment for covariates, handling of missing data, and adherence to assigned treatment are not reported. The record's analysis count is 0 even though outcome summaries and comparisons are posted, and it does not explain that record-level discrepancy.

The outcomes available for interpretation are incomplete relative to the stated aims. Self-reported pain-score results and length-of-stay results are not reported in the registry record. The registry lists narcotic-associated side effects, but no broader summary of all aspects of recovery is available in the posted results. Safety observation details are not reported, and the death figures are not reported in the registry record.

The primary endpoint is an inpatient opioid-use measure, with a timeframe of approximately 2 - 7 days. It cannot on its own establish longer-term outcomes or directly quantify pain. The group standard deviations indicate variation in the endpoint, and the posted result is a group-average contrast rather than an account of individual responses. The registry also does not identify which parties were masked or describe the procedures used to maintain masking. These are reporting limitations, not proof that the trial did not use such procedures.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: RCT (Randomized Controlled Trial) of IV Acetaminophen for Post Cesarean Pain Relief — NCT02046382.
• Registry record last updated 2018-08-16; status last verified 2018-02.
• Results first posted 2018-01-23.
• 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

NCT02046382 is a completed, randomized, triple-masked, parallel-group phase 4 trial sponsored by TriHealth Inc. The registry records enrollment of 132, a start of 2014-01, and primary completion in 2016-12. It compared scheduled intravenous acetaminophen with normal saline after cesarean delivery.

The primary endpoint was total oxycodone in mg for breakthrough pain during the inpatient stay, with a timeframe of approximately 2 - 7 days. The posted means were 47.0 mg for intravenous acetaminophen and 65.0 mg for normal saline. The reported mean difference was 18.0 mg in the normal-saline-relative-to-acetaminophen direction, with a confidence interval from 1.342 to 34.66 and an unadjusted p value of 0.034.

The record lists narcotic-associated side effects and length of stay as secondary outcomes. Length-of-stay results and self-reported pain-score results are not reported in the registry record. The original sample-size justification, detailed analysis plan, and missing-data procedures are also not reported.