Analgesic Efficacy of Repeated Doses of Intravenous (IV) Acetaminophen in Post-operative Pediatric Spine Fusion Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Analgesic Efficacy of Repeated Doses of Intravenous (IV) Acetaminophen in Post-operative Pediatric Spine Fusion Patients (NCT01394718), a randomized phase 3 study. The primary outcome is Total Opiate Requirement.

2. Clinical Question

The registry record describes a trial in children undergoing spinal fusion, with postoperative pain as the condition of interest. The central question is whether repeated intravenous acetaminophen, given alongside usual patient-controlled opioid analgesia, is associated with different opioid requirements during the first postoperative 24 hours than saline placebo alongside usual care.

The outcome is a comparison between assigned groups, not a comparison of opioid use before and after treatment within the same patients. The posted group means are 1.19 mg/kg for saline placebo and 1.01 mg/kg for intravenous acetaminophen. The unadjusted mean difference is -0.18 mg/kg for acetaminophen relative to placebo. These summaries describe the observed participants; they do not by themselves establish a causal effect with high precision or show whether any difference is important to patients.

3. Trial Design

The registry identifies this as a completed, randomized, parallel-group phase 3 trial sponsored by Children's Hospital of Philadelphia. It lists quadruple masking. The brief summary calls the study double-blinded, so the registry record uses different masking descriptions in those fields; further details clarifying the masking procedures are not reported in the registry record. The recorded enrollment is 67.

Participants were assigned to intravenous acetaminophen or saline placebo. The first study-drug dose was administered at skin closure. Doses were scheduled every 6 hours; the arm descriptions specify 42 hours of postoperative acetaminophen and 44 hours of postoperative saline. The stated schedules therefore differ in duration. Both groups also received standard-of-care patient-controlled opioid therapy, using morphine or hydromorphone as directed by the Pain Management Service.

The primary outcome was measured over 24 hours. Pain scores, opioid use, treatment for opioid-related nausea or itching, and postoperative characteristics were described as being monitored for up to 4 days. The registry lists average pain, nausea, and pruritus scores as secondary outcomes. The posted primary outcome summaries include 28.0 participants in the saline group and 29.0 in the acetaminophen group. The available secondary outcome results include average pain score; numerical results for average nausea and pruritus are not reported in the registry record.

The original protocol's allocation details, concealment procedures, full statistical analysis plan, and rationale for the target enrollment are not reported in the registry record. The listed enrollment should not be treated as proof that the trial achieved a particular planned sample size or power.

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.

Before assignment: 281 subjects were screened, 125 approached for consent/assent and 67 consented/assented. Of the initial 67 subjects, 1 was withdrawn by the clinical team, 1 patient's surgery was cancelled, 2 were withdrawn by the family, and 3 were deemed ineligible after consent were removed from the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects were deemed evaluable if a minimum of 24 hours of data was collected post-operatively, with receipt of at least four doses of study drug, prior to study withdrawal or unblinding, with T0 (time zero) being time of administration of first dose of either treatment drug or placebo.

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.

Population: Analysis population includes only those subjects who completed at least 24 hours of post-operative data collection. 3 subjects who were enrolled and received at least 1 dose were removed before reaching the 24 hour post-operative milestone.

6. Primary Endpoint

The registry lists the primary outcome as Total Opiate Requirement, measured over 24 hours.

The primary endpoint is total opiate requirement during the first 24 hours after surgery. The registry says morphine and hydromorphone measurements were totaled and recorded as morphine equivalents in mg/kg/day. This common scale allows opioid use involving either named drug to be represented in a single outcome, rather than treating each drug as a separate endpoint. The listed endpoint unit is mg/kg.

Opioid requirement is relevant to the trial's analgesia question because both groups received opioid-based standard care, while the randomized study treatment was acetaminophen or saline. The endpoint therefore compares opioid use under those two assigned regimens; it is not a direct measurement of pain itself. Pain was separately listed as a secondary outcome.

The registry defines an evaluable participant as one with at least 24 hours of postoperative data, receipt of at least four study-drug doses, and measurement before study withdrawal or unblinding. Time zero was the first dose of study drug or placebo. This definition matters when interpreting the posted arm sizes: they describe the reported outcome population, while the registry enrollment is 67. The reasons some enrolled participants are not represented in the primary outcome summaries are not reported in the registry record.

The group means are 1.19 mg/kg for saline placebo and 1.01 mg/kg for intravenous acetaminophen. A mean is a measure of the group's average outcome, while the standard deviations describe the spread of individual values around those averages. The endpoint can summarize group-level opioid consumption, but the mean and standard deviation do not show every participant's use or its distribution.

7. Results Posted in the Registry

• Intravenous Acetaminophen: mean 1.01 versus 1.19 on control; difference -0.18 (95% CI -0.38 to 0.02), standardized effect d = -0.48; z-test p = 0.074.

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.

Average Pain Score

• 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:
  • Intravenous Acetaminophen: mean 4.62 versus 4.53 on control; difference 0.09 (95% CI -0.95 to 1.13), standardized effect d = 0.04; z-test p = 0.865.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intravenous Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists average pain score, average nausea score, and average pruritus score as secondary outcomes. Numerical results are posted for average pain score, while results for nausea and pruritus are not reported in the registry record. The available pain result shows group means close to one another, with an unadjusted mean difference whose interval includes zero and an unadjusted p-value of 0.865.

Across the outcomes with numerical summaries, the pattern does not provide a clear, precise separation between groups: the primary opioid-use estimate favors a lower observed mean in the acetaminophen arm, while the average pain estimate is close to zero and points slightly in the opposite direction. This is a descriptive comparison of the posted summaries, not evidence that opioid use and pain necessarily move together or that one outcome explains the other. The registry does not report individual-level relationships between opioid use and pain scores.

Secondary outcomes can help characterize other aspects of the postoperative experience, but they are not interchangeable with the primary endpoint. Pain score, nausea score, and pruritus score concern different measures from total opioid requirement. Their interpretation depends on their definitions, timing, completeness, and analysis methods, which are not fully reported in the registry record.

Unadjusted secondary comparisons generally carry less weight than a prespecified primary analysis because testing several outcomes creates more opportunities for an apparently notable result to arise by chance. General statistical explanation: multiplicity procedures can control error rates across a family of tests, but the registry does not report whether any such procedure was planned or used. With results absent for two listed secondary outcomes and no reported analyses, the secondary record cannot establish a comprehensive pattern across all listed measures.

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

• Average Pain Score
• Average Nausea Score
• Average Pruritus Score

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a measured quantity, total opiate requirement, summarized using a mean and standard deviation. A mean difference expresses the group contrast in the original measurement units. In this comparison the contrast is defined as the acetaminophen mean minus the placebo mean, so the estimate of -0.18 mg/kg points toward a lower observed mean in the acetaminophen group. This direction convention is important: reversing the group order would reverse the sign but not change the underlying comparison.

What does the standard deviation describe?

General statistical explanation: the standard deviation describes how spread out individual observations are around the group mean. It is not the uncertainty in the mean difference itself. The registry reports standard deviations of 0.43 for placebo and 0.32 for acetaminophen. A group can have a relatively broad spread of individual outcomes even when its mean is estimated more precisely, and the mean's precision also depends on how many participants contribute data.

What does the mean difference tell us?

General statistical explanation: a difference in means summarizes the average separation between groups on the outcome scale. It does not describe every participant's response, establish the shape of the outcome distribution, or explain why individuals differ. Here the estimated mean difference is -0.18 mg/kg. Its interpretation depends on the assigned contrast, the outcome definition, and the reliability of the data used to calculate it. The registry does not report a threshold for a clinically important difference, so statistical size alone cannot determine clinical importance.

How should the p-value be read?

General statistical explanation: a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor the probability that the result occurred by chance. The posted unadjusted p-value for the primary comparison is 0.074. It does not quantify the chance that the treatment has no effect, and it should not be used alone to judge the size, direction, or importance of the estimate. The registry does not report the sponsor's analysis procedure or a full analysis plan, so the recalculated comparison should be understood as an unadjusted summary-statistic analysis.

Why is the interval useful?

General statistical explanation: a confidence interval gives a range of values compatible with the data under a particular statistical method and its assumptions. It communicates uncertainty about the effect estimate, not the range containing most individual participants. The interval for the primary mean difference crosses zero, indicating that values consistent with the posted summaries include both a negative and a positive group difference. Its width is therefore important alongside the point estimate. The registry does not report the interval's confidence level or the exact method used by a sponsor, and the recalculated comparison is not a reported sponsor analysis.

What assumptions accompany a comparison of means?

General statistical explanation: a conventional unadjusted comparison of means relies on assumptions about the sampling process and the behavior of the estimate. Normal-approximation methods are often more dependable when observations are independent and the sampling distribution of the mean difference is reasonably well behaved. Unequal outcome variability, extreme observations, skewness, or dependence among observations can affect how well a simple method represents uncertainty. The registry gives group standard deviations and sample sizes but does not provide participant-level data, distributions, or diagnostic checks. It is therefore not possible to assess those features from the posted summaries alone.

The study used random allocation according to the registry. In general, randomization supports a fair comparison by reducing systematic differences in expectation between assigned groups, but it does not ensure that the realized groups are identical, especially in a modest sample. Masking may limit some differences in care or measurement, but the registry's brief summary and design fields use different masking descriptions, and procedural details are not reported in the registry record.

The posted primary estimate is recalculated from the group summaries. Its role is descriptive: it supplies an unadjusted estimate of the contrast and uncertainty based on the posted means, standard deviations, and group sizes. The registry lists no reported analyses, so there is no posted adjusted result or documented inferential procedure to compare with this recalculation. The analysis population, handling of missing observations, and any prespecified covariates are not reported in the registry record.

The primary endpoint's evaluability rule also affects interpretation. A participant needed at least 24 hours of data and at least four study-drug doses before withdrawal or unblinding. Such a rule defines which data qualify for the reported endpoint, but the registry does not describe how participants who fail that rule were handled in the original analysis. General statistical principle: excluding participants based on post-randomization events can affect the balance created by randomization if the exclusions are related to outcomes or group assignment. Whether that issue arose in this trial cannot be determined from the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -0.18 mg/kg, with an unadjusted interval extending from -0.377 to 0.017. The interval includes zero and includes both a negative and a positive contrast. Thus the posted summaries are compatible with a lower mean in the acetaminophen group, little or no difference, or a slightly higher mean within the displayed bounds. This range conveys uncertainty that the point estimate alone would conceal.

The group means are 1.19 mg/kg for placebo and 1.01 mg/kg for acetaminophen. Their standard deviations are 0.43 and 0.32, respectively, and the outcome summaries use 28.0 and 29.0 participants. These sample sizes are modest, and the interval remains broad relative to the estimated difference. The interval should not be interpreted as a range of individual opioid requirements; it concerns the group contrast under the recalculation's statistical assumptions.

The posted primary comparison is recalculated from summary statistics and is unadjusted. The registry does not report a sponsor analysis or the interval's confidence level and construction method. For those reasons, the interval is useful as a measure of uncertainty around the posted contrast, but it cannot substitute for a complete account of the trial's analysis plan. The unadjusted p-value is 0.074, consistent with the interval's inclusion of zero in this comparison.

Precision is distinct from clinical importance. The registry does not report a threshold for a meaningful difference in opioid requirement, and the interval alone cannot identify such a threshold. It does show that the estimate is not precise enough to pin down the group contrast to a narrow range around the observed value.

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 based on the observed effect in the posted comparison, with alternative scenarios using 75% and 50% of that observed effect. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For these continuous outcomes the figures are participants per arm, not total event counts.

For the primary endpoint, planning for 100% of the observed effect gives 70 participants per arm for 80% power and 93 participants per arm for 90% power. Planning for 75% of the observed effect gives 124 and 165 participants per arm, respectively. Planning for 50% of the observed effect gives 277 and 371 participants per arm, respectively. The pattern reflects a general statistical relationship: smaller effects are harder to distinguish from random variation, so detecting them at the same power generally requires more participants.

Power is the probability, under a specified effect and model, of obtaining a statistically significant result. The 80% and 90% columns represent different target probabilities under the stated planning assumptions; aiming for higher power requires a larger planned sample in these illustrations. These figures are planning illustrations based on the observed effect, not the original trial design assumptions, which are not reported in the registry record. They are not observed power, and they do not indicate the probability that the trial's conclusion is correct.

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 = -0.180; pooled standard deviation σ = 0.378.
2. n = 2 × (1.96 + 0.842)² × 0.378² / -0.180² = 69.2, rounded up to 70 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 <- -0.18                      # observed difference in means
sigma <- 0.378021163428716                     # 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(1394718)
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 = 70 (80% power), 93 (90% power)
 75% of observed effect: n per arm = 124 (80% power), 165 (90% power)
 50% of observed effect: n per arm = 277 (80% power), 371 (90% power)
power.t.test: 70.2 
Simulated power at n = 70 per arm: 0.802 (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 identifies one primary outcome, total opiate requirement, and lists average pain, nausea, and pruritus as secondary outcomes. It does not report a complete statistical analysis plan, the number of hypotheses formally tested, or any multiplicity adjustment. The posted secondary data include numerical results for average pain; numerical results for nausea and pruritus are not reported in the registry record. No reported analyses are listed.

General statistical explanation: when multiple outcomes or multiple comparisons are examined, the chance of at least one apparently unusual result can increase. A prespecified hierarchy or adjustment method can address that concern, but neither the use nor the absence of such a method can be established from the registry record. The primary comparison's unadjusted p-value should therefore not be treated as evidence that all outcome testing was controlled as a family. Secondary comparisons warrant particular caution because their relationship to the primary question and their place in a testing plan are not described.

The record describes an evaluable population for the primary endpoint: participants needed at least 24 hours of postoperative data and at least four study-drug doses before withdrawal or unblinding. It does not report how many randomized participants failed those criteria, why any data were unavailable, or what missing-data method was used. The record also does not say whether the main analysis followed an intention-to-treat principle or another analysis population definition. The listed arm sizes for the primary outcome are 28.0 and 29.0, while the recorded enrollment is 67; the reason for the difference in these counts is not reported in the registry record.

General statistical explanation: missing data can affect estimates if the probability of having an observed outcome is related to treatment assignment or to the outcome itself. Excluding participants under a post-randomization evaluability rule can also change the composition of the groups being compared. Without participant flow, reasons for missingness, and sensitivity analyses, the direction or size of any such effect cannot be determined. These gaps limit assessment of how robust the reported summaries are to missing outcomes and exclusions.

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 safety figures report zero participants affected by serious adverse events in the saline placebo group, among 28 participants at risk, and zero in the intravenous acetaminophen group, among 29 participants at risk. It also reports zero participants affected by other adverse events in each group, using the same respective at-risk counts. These are counts of participants affected, not a complete description of event severity, timing, or possible relationship to study treatment.

The deaths field is null for both groups, so deaths are not reported in the registry record; a null entry should not be rewritten as a reported zero. The serious adverse event terms list is empty. The registry does not provide event-level descriptions, follow-up-specific safety details, or an explanation of whether the absence of listed events reflects no events or limited reporting.

These registry figures describe what was posted for the recorded at-risk groups. They do not establish that an event could not occur, and the sample sizes are limited. Safety interpretation should therefore remain bounded to the recorded counts and should not be extended to unreported events or populations.

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

The posted primary outcome summaries show a mean total opiate requirement of 1.19 mg/kg in the saline placebo group and 1.01 mg/kg in the intravenous acetaminophen group over 24 hours. The unadjusted mean difference is -0.18 mg/kg. Its interval crosses zero, and the unadjusted p-value is 0.074. These data describe a lower observed group mean with acetaminophen, but leave uncertainty about the size and direction of the underlying group difference.

The result does not establish equivalence. A non-significant comparison is not proof that the treatments have the same effect; it can also reflect imprecision. Nor does the result establish that acetaminophen reduces opioid use. The interval includes contrasts in both directions, and the registry record does not provide a reported sponsor analysis or a full statistical plan. No threshold for a clinically important difference in opioid requirement is reported, so the statistical estimate alone cannot determine whether a difference would matter in practice.

The endpoint measures opioid consumption, while pain was listed as a separate secondary outcome. The posted average pain summaries do not establish a clear group difference either, and outcomes for nausea and pruritus are not reported in the registry record. The primary result should not be interpreted as a complete account of analgesia, side effects, mobility, diet advancement, or discharge. Although the registry says some postoperative characteristics were to be measured, numerical results for those characteristics are not reported in the registry record.

The appropriate conclusion is limited: among the participants represented in the posted primary summaries, the observed opioid-use mean was lower in the acetaminophen group, with substantial uncertainty around the unadjusted contrast. The available record does not support stronger claims about the size, certainty, clinical importance, or broader consequences of that contrast.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an estimated direction and a well-resolved treatment contrast. The observed primary mean is lower in the acetaminophen group, but the unadjusted interval crosses zero and the p-value is 0.074. Reporting only the direction of the point estimate would overstate what the data settle; reporting the interval makes the uncertainty explicit.

The example also shows why endpoint definitions matter. Total opioid requirement was calculated from morphine and hydromorphone measurements expressed as morphine equivalents, whereas pain was a separate secondary measure. A result on one outcome should not be treated as a direct substitute for another. The registry's evaluability criteria further identify which participants qualified for the primary outcome summaries, making the analysis population relevant to interpretation.

Planning figures based on the observed effect make another statistical issue visible: a study sized around a particular observed contrast may require substantially more participants per arm if the target effect is smaller or if higher power is sought. Such figures are illustrations, not evidence about the trial's original planning or its observed power. The registry does not report its original sample-size justification.

Finally, the record separates what can be learned from posted summaries from what remains unavailable. Numerical data for some listed secondary outcomes, the analysis plan, missing-data procedures, and detailed safety descriptions are not reported in the registry record. This distinction helps readers avoid interpreting an incomplete set of results as a full account of every outcome or every analysis.

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 primary group summaries include 28.0 participants in the placebo arm and 29.0 in the acetaminophen arm, while the registry records enrollment of 67. The reasons those counts differ are not reported in the registry record. The evaluability rule required at least 24 hours of data and at least four study-drug doses before withdrawal or unblinding, but participant flow and the handling of those not meeting the rule are not described. This limits assessment of whether the outcome summaries preserve the benefits of randomization.

The registry lists no reported analyses. The primary comparison is an unadjusted recalculation from the posted summaries, and the full statistical plan, any covariate adjustment, and the sponsor's analysis procedure are not reported in the registry record. The record also does not describe distributional checks, sensitivity analyses, or procedures for missing outcomes.

The brief summary calls the trial double-blinded, whereas the design field identifies quadruple masking. The record does not clarify how masking was implemented. The arm descriptions specify different postoperative study-drug durations: 42 hours for acetaminophen and 44 hours for saline. The registry does not explain the difference. These documentation features do not by themselves establish a flaw, but they limit detail available for judging conduct and interpretation.

Numerical results for nausea and pruritus are not reported in the registry record, despite their listing as secondary outcomes. Safety reporting is limited to participant counts affected, with deaths not reported and no serious-event terms listed. The registry also does not report a threshold for clinically important differences. Together, these gaps constrain conclusions about secondary effects, missingness, analysis robustness, and the practical importance of the primary estimate.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Analgesic Efficacy of Repeated Doses of Intravenous (IV) Acetaminophen in Post-operative Pediatric Spine Fusion Patients — NCT01394718.
• Registry record last updated 2016-04-18; status last verified 2016-03.
• Results first posted 2016-04-18.
• 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 describes a completed, randomized, parallel-group phase 3 trial comparing repeated intravenous acetaminophen with saline placebo in pediatric spinal fusion patients. Both groups received standard-of-care patient-controlled opioid therapy. The primary endpoint was total opiate requirement over 24 hours, expressed as morphine equivalents.

The placebo and acetaminophen group means were 1.19 mg/kg and 1.01 mg/kg, respectively. The unadjusted mean difference was -0.18 mg/kg, with an interval crossing zero and an unadjusted p-value of 0.074. The posted estimate points toward a lower observed mean with acetaminophen but remains uncertain.

The registry lists average pain, nausea, and pruritus as secondary outcomes, but numerical results are available only for average pain. It reports zero participants affected by serious or other adverse events in each arm; deaths are not reported. The analysis plan, missing-data handling, and original sample-size justification are not reported in the registry record.