Efficacy of IV Acetaminophen Versus Oral Acetaminophen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of IV Acetaminophen Versus Oral Acetaminophen (NCT03365622), a randomized phase 4 study. The primary outcome is Total Opioid Dose (MME) Used in 24 Hours.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase 4 clinical study. The registry lists an enrollment of 214 and a completed status. The study start date is 2018-08-08, and the primary completion date is 2024-04-10. The sponsor is the University of Rochester. The registry title describes an evaluation of intravenous versus enteric acetaminophen in donor nephrectomy and robot-assisted, laparoscopic nephrectomy.

The study compared intravenous acetaminophen with placebo pills against placebo IV, identified as normal saline, plus oral acetaminophen. The brief summary describes the two surgical populations as patients scheduled for laparoscopic donor nephrectomy and patients scheduled for robot-assisted, laparoscopic nephrectomy for cancer at the University of Rochester Medical Center. Standard surgical and post-operative care, including post-operative pain management, was not to be altered according to that summary.

The primary endpoint concerns total opioid dose in morphine milligram equivalents through 24 hours post-operatively, including intra-operative administration. The record also lists secondary measures covering surgical pain, inspiratory capacity, dynamic pain during incentive spirometer use, pain at the 20-24 hour assessment, and time to first narcotic use. Numerical secondary results are available for some, but not all, of those measures.

The registry describes the primary comparison using linear regression and a mean difference in final values. Details of the trial's original sample-size justification, randomization procedure, allocation concealment, analysis populations, and missing-data handling are not reported in the registry record. The masking label is quadruple, but the identities of all masked parties are not specified 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.

Before assignment: There were 57 subjects who were withdrawn, however 6 of those subjects were included in the intent to treat analysis. as they did receive one dose of study medication.

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 Opioid Dose (MME) Used in 24 Hours, measured over 20 to 24 hours post-operatively.

The primary endpoint is total opioid dose, expressed in morphine milligram equivalents (MME), over the period from the study start—when the first acetaminophen dose is administered in the pre-anesthesia holding area—through 24 hours post-operatively. The description explicitly includes opioids administered during the operation. The outcome is recorded as a mean with standard deviation, and the listed timeframe is 20 to 24 hours post-operatively.

MME expresses opioid doses using a common unit, allowing total opioid exposure from the included administrations to be summarized on a shared scale. A mean describes the average amount recorded in each group; the standard deviation describes how much individual values vary around that group average. These are general statistical interpretations of the measure, not additional results from the trial.

Opioid use was selected as the primary measure of interest in this comparison of acetaminophen routes. It captures opioid administration across the stated perioperative period, rather than pain intensity alone. The endpoint description does not say how opioid use was analyzed when a participant had missing doses or incomplete follow-up, and such handling is not reported in the registry record. The recorded outcome timeframe and the detailed endpoint interval are worded differently in the registry; the record does not explain that distinction.

7. Results Posted in the Registry

• Placebo IV (Normal Saline) + Oral Acetaminophen: mean 109.17 versus 103.61 on control; difference 5.56 (95% CI -9.95 to 21.07), standardized effect d = 0.10; z-test p = 0.482.

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 Surgical Pain Intensity

• 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:
  • Placebo IV (Normal Saline) + Oral Acetaminophen: mean 5.00 versus 4.87 on control; difference 0.13 (95% CI -0.44 to 0.70), standardized effect d = 0.06; z-test p = 0.653.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo IV (Normal Saline) + Oral Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

Mean Inspiratory Capacity

• 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:
  • Placebo IV (Normal Saline) + Oral Acetaminophen: mean 67.07 versus 66.60 on control; difference 0.47 (95% CI -5.10 to 6.04), standardized effect d = 0.02; z-test p = 0.869.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo IV (Normal Saline) + Oral Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

Dynamic Pain Score During Incentive Spirometer Use

• 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:
  • Placebo IV (Normal Saline) + Oral Acetaminophen: mean 5.15 versus 4.73 on control; difference 0.42 (95% CI -0.29 to 1.13), standardized effect d = 0.16; z-test p = 0.246.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo IV (Normal Saline) + Oral Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

The numerical secondary results cover average surgical pain intensity, mean inspiratory capacity, and dynamic pain score during incentive spirometer use. Across those results, the reported group contrasts are small relative to the intervals around them, and each reported interval includes zero. This broad pattern does not supply a clear secondary-outcome signal that changes the interpretation of the primary comparison. It should not be taken as proof that the groups are equivalent on these measures.

These outcomes address related but distinct aspects of post-operative experience and function. Pain scores are not the same measure as total opioid dose, and inspiratory capacity is a different type of outcome again. Agreement in broad statistical direction across measures can offer context, but it does not make the secondary outcomes interchangeable or establish a common treatment effect. The primary outcome remains the designated main comparison in the registry record.

The registry lists other secondary outcomes, including surgical pain at the 20-24 hour assessment and time to first narcotic use. Numerical summaries for those outcomes are not reported in the registry record. The record identifies 11 secondary outcomes as posted, but the detailed numerical information available for interpretation is incomplete in the registry record.

Unadjusted secondary results generally carry less weight when many outcomes are assessed, because multiple testing can make at least one result appear noteworthy even without a consistent underlying effect. The registry does not report a multiplicity adjustment, a prespecified hierarchy for secondary endpoints, or a plan distinguishing confirmatory from exploratory comparisons. Thus, secondary outcomes can provide context for the primary result, but should not be treated as independent definitive tests without those design details.

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

• Average Surgical Pain Intensity
• Average Surgical Pain Intensity
• Mean Inspiratory Capacity
• Mean Inspiratory Capacity
• Dynamic Pain Score During Incentive Spirometer Use
• Dynamic Pain Score During Incentive Spirometer Use
• Surgical Pain Score During the 20-24 Hour Assessment
• Time to First Narcotic Use

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a linear-regression analysis of the primary outcome, with the parameter described as a mean difference in final values. Alongside it, an unadjusted recalculation compares the posted group means using their standard deviations and group sizes. These approaches answer related questions but are not identical: the recalculation is based directly on summary statistics, while the registry's reported analysis is a regression. The covariates, if any, in that regression are not reported in the registry record.

What does a mean difference represent?

A mean difference subtracts one group's average from the other group's average. The recalculated primary comparison is oriented as the oral-acetaminophen group minus the intravenous-acetaminophen group. A positive estimate therefore indicates a higher observed group mean in the oral-acetaminophen arm; a negative estimate indicates a lower mean in that arm. This direction describes the numerical comparison, not a judgment about benefit. Interpretation also depends on the outcome's meaning and the range of values compatible with the confidence interval.

The reported group means are 103.6 MME and 109.2 MME, with standard deviations of 58.16 and 57.59. Standard deviation is a description of variation among individual observations, not a measure of uncertainty in the group mean. The standard error instead describes the sampling uncertainty of an estimated mean. The posted standard errors for the two primary group means are 5.596 and 5.594. General statistical explanation: standard errors are used to quantify the uncertainty involved in estimating a population quantity from a sample.

How should the confidence interval be read?

The recalculated 95% confidence interval for the mean difference runs from -9.948 to 21.07 MME. In general, a confidence interval gives a range of values compatible with the observed data under the analysis assumptions and conveys precision as well as direction. Because this interval crosses zero, the summary-statistic comparison does not rule out no difference; it also permits differences in either direction. A confidence interval is not a guarantee that the true value lies within the particular interval, and it does not assign a probability to each value in the range.

The registry's linear-regression estimate is 6.306, with a 95% confidence interval from -8.242 to 20.854. Differences between that estimate and the recalculated estimate can arise because the procedures are different. The record does not describe enough of the regression specification to explain the difference further. The discrepancy indicator is false, but that does not make the two estimates the same or remove the distinction between the sponsor's reported analysis and the unadjusted recalculation.

What does the p-value add?

The recalculated unadjusted p-value is 0.482, and the reported regression p-value is 0.394. In general, a p-value evaluates how unusual the data would be under a null model of no difference, given the model's assumptions. It is not a measure of the probability that the null hypothesis is true, and it does not state the probability that a result occurred by chance. A p-value alone does not show whether a difference is important; the estimate and interval are needed to understand its direction and precision.

The registry identifies a superiority analysis. A superiority test asks whether the evidence supports a difference in the specified direction or across the groups, depending on the test specification. The record does not report whether the test was one- or two-sided, its prespecified decision threshold, or additional details of the analysis plan. The separate planning illustration specifies a two-sided significance level of 0.05, but those are planning assumptions for that illustration and not evidence about the trial's original analysis plan.

Why do analysis choices matter?

Randomization is intended to support a fair comparison by assigning participants to study groups without selecting their treatment on the basis of prognosis. In general, analyses can nevertheless differ in how they handle baseline characteristics, missing observations, and the population included. The registry labels the study randomized but does not report the randomization method, allocation concealment, analysis population, or missing-data method. It is therefore not possible to assess those details from the registry record.

The primary outcome is continuous and summarized by means and standard deviations. General statistical explanation: mean-based methods are most directly interpretable when the outcome and model assumptions are suitable; unusual distributions or influential values can affect means and regression estimates. The registry does not report diagnostics or distributional details for opioid use, so those features cannot be evaluated from the posted summary.

Multiplicity is another general concern when several outcomes are tested. If many tests are interpreted without a prespecified strategy, the chance of at least one apparently unusual result can increase. The registry lists multiple secondary outcomes, but an adjustment approach or hierarchy for interpreting them is not reported in the registry record. The secondary results should consequently be treated as supportive or exploratory rather than as independent confirmation of the primary result unless the full analysis plan establishes otherwise.

11. Confidence Intervals and Precision

The primary unadjusted mean difference is 5.56 MME, and its 95% confidence interval extends from -9.948 to 21.07. This interval is wide enough to include zero and values on either side of it. It therefore conveys uncertainty about both the direction and size of the difference, rather than locating the effect precisely around the point estimate. The standard deviations, 58.16 and 57.59, also show substantial variation in individual opioid-dose observations relative to the group means, though they do not alone determine the confidence interval.

The registry's regression estimate is 6.306, with a 95% confidence interval from -8.242 to 20.854. The two intervals are similar in that both include zero and allow for effects in either direction, but their endpoints differ because one analysis is a regression and the other is an unadjusted recalculation from posted summary statistics. The registry does not report the regression covariates or other modeling details needed to explain that difference more specifically.

In general, a confidence interval's width reflects statistical precision: narrower intervals indicate less uncertainty about the estimate, while wider intervals leave a broader range of values compatible with the data and model. Precision is not the same as clinical importance. A narrow interval could still include effects that matter, and a wide interval can leave important possibilities unresolved. The registry does not report a threshold for a clinically important MME difference or an equivalence margin, so the clinical implications of the interval cannot be judged against a stated benchmark.

The enrollment figure alone does not determine precision. Variation in opioid use and the analysis method also matter, and the actual analyzed group sizes are listed with the posted outcome. The confidence interval should be interpreted as uncertainty around the estimated group contrast, not as a range containing individual patients' doses.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not a record of the trial's original design calculation. They are expressed as participants per arm for 80% power and participants per arm for 90% power. The 80% column means the illustrative design would have an 80% chance of detecting the stated effect under its assumptions if that effect were real; the 90% column represents a higher target chance under the same framework. These are planning probabilities, not guarantees for a particular study.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The row labels describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects require more participants to detect with the same power, which is why the planning figures increase as the target effect becomes a smaller fraction of the observed effect.

For this continuous outcome, the figures are participants per arm, not total events. The record's general note distinguishes these from time-to-event illustrations, which would be reported as total events; that is not the format for this outcome. The displayed estimates should be read as conditional illustrations: changing the target effect or assumptions would change the planning result. The original trial's own sample-size assumptions and justification are not reported in the registry record. These figures are not observed power; they are prospective planning illustrations calculated from the observed effect, not a measure of what the completed trial achieved.

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 = 5.560; pooled standard deviation σ = 57.878.
2. n = 2 × (1.96 + 0.842)² × 57.878² / 5.560² = 1,701.1, rounded up to 1,702 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 <- 5.56                      # observed difference in means
sigma <- 57.8783903078052                     # 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(3365622)
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 = 1,702 (80% power), 2,278 (90% power)
 75% of observed effect: n per arm = 3,025 (80% power), 4,049 (90% power)
 50% of observed effect: n per arm = 6,805 (80% power), 9,109 (90% power)
power.t.test: 1702 
Simulated power at n = 1,702 per arm: 0.797 (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. Analyses Reported by the Sponsor

The registry reports the sponsor's primary analysis as linear regression, with a mean difference in final values of 6.306, a 95% confidence interval from -8.242 to 20.854, and p = 0.394. The unadjusted recalculation from the posted group means, standard deviations, and group sizes gives a mean difference of 5.56, a 95% confidence interval from -9.948 to 21.07, and p = 0.482. The recalculation is not a substitute for the sponsor's analysis: it does not reproduce a regression model, and the registry does not report the model specification in enough detail to do so.

Both analyses yield confidence intervals spanning zero and neither provides clear statistical evidence of a difference in the primary outcome. Their estimates and p-values are not identical, which is expected when a regression analysis and an unadjusted summary-statistic calculation use different procedures. The discrepancy indicator is false. The registry record does not report enough methodological detail to determine whether the regression adjusted for particular variables or handled observations in a particular way.

The sponsor's reported analysis is the trial's own posted analysis and should be distinguished from the recalculation rather than blended with it. Neither estimate alone demonstrates equivalence or establishes the clinical importance of possible differences; the record does not provide an equivalence margin or an MME threshold for clinical importance.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, and the posted record includes several comparisons. Testing multiple outcomes creates a multiplicity issue: as the number of statistical tests grows, interpreting each result using an unadjusted threshold can increase the chance of a misleading positive finding. This is a general statistical concern, not evidence that any particular result in this trial is false.

An analysis plan may address multiplicity through a hierarchy of endpoints, adjustment procedures, or a clear designation of exploratory outcomes. Such an approach is not reported in the registry record. The record also does not report whether the primary outcome was the sole confirmatory endpoint or how secondary comparisons were intended to support interpretation. Consequently, the secondary results should be read cautiously and in the context of the primary outcome.

The registry record does not describe how missing outcome data were handled, whether participants with incomplete data were included in particular analyses, or whether any sensitivity analyses were conducted. It also does not specify the analysis populations, such as whether the primary analysis followed assignment regardless of treatment received. The outcome-specific group sizes vary in the posted summaries, but the record does not explain why they differ or how missingness was addressed.

These omissions limit assessment of possible bias. In general, missing data can affect a comparison if the likelihood of an observation being missing is related to treatment or outcome, and different analysis populations can answer different questions. The registry's posted estimates remain interpretable as reported summaries and analyses, but the available record does not permit a full evaluation of these choices. Details of the prespecified statistical analysis plan are not reported in the registry record.

16. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cognitive and attention disorders (0.9%), urinary tract infections and epididymal and testicular infections (0.9%), anemias non-hemolytic and marrow depression (0.9%).

The serious adverse event listing records 1 affected participant in the intravenous acetaminophen and placebo pills group, with 108 at risk, and 1 affected participant in the placebo IV plus oral acetaminophen group, with 106 at risk. Deaths are listed as 0 in both groups. These are the registry's posted figures; they do not establish that all safety outcomes were captured or that there were no other harms.

The record lists three serious-event terms with a displayed percentage of 0.9% for each: cognitive and attention disorders; urinary tract infections and epididymal and testicular infections; and anemias non-hemolytic and marrow depression. The registry information does not specify in this summary how those terms map to the individual group listings, so they should not be assigned to a particular arm based on these figures alone.

Other adverse events are listed as affecting 14 participants in the intravenous group and 16 in the oral group. The registry does not provide enough detail to characterize their severity, duration, relatedness to treatment, or clinical importance. Counts of adverse events are descriptive and should be considered alongside the completeness and definitions of safety reporting, which are not detailed in the registry record.

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

The registry results describe a randomized comparison of intravenous acetaminophen and oral acetaminophen in nephrectomy patients, with total opioid use through 24 hours post-operatively as the primary measure. The posted means are close in scale, and both the registry's regression analysis and the unadjusted recalculation have confidence intervals that include zero. The results therefore do not establish a statistically clear difference in the primary outcome.

That finding does not prove that the regimens have identical effects. The intervals leave room for a range of possible differences, and the registry does not state an equivalence margin or a threshold for a clinically important difference in MME. Nor does a non-significant result show that either approach is effective or ineffective in general. It describes the evidence available for this comparison and outcome, in the trial's recorded setting and population.

The findings also do not address every relevant aspect of post-operative care. The primary endpoint is total opioid dose over a defined period; pain intensity, inspiratory capacity, and other secondary outcomes are separate measures. The study summary says standard surgical and post-operative care, including pain management, was not to be altered, but the record does not provide details sufficient to interpret all care components or their contributions to outcomes.

The study's limitations in the registry record include unavailable detail on the original design assumptions, analysis populations, missing-data methods, multiplicity strategy, and regression specification. Those omissions make it difficult to assess some sources of uncertainty beyond the statistical intervals. The appropriate conclusion is bounded: the posted results do not show a clear between-group difference in the primary outcome, while the precision and unreported design details prevent a claim of equivalence or a broad clinical conclusion.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate and a significance test are not enough to interpret a clinical comparison. The primary mean difference is accompanied by a confidence interval that spans zero and includes values on either side. That combination makes the uncertainty visible: the point estimate alone may suggest a direction, but the interval shows that the evidence is compatible with other directions and magnitudes as well.

It also illustrates the distinction between a sponsor-reported model and an unadjusted recalculation. Both are useful to identify and compare, but they are not interchangeable. The regression result reflects the analysis reported in the registry, while the summary-statistic calculation offers a transparent, simple comparison based on group means and variability. The record's limited description of the regression prevents a more detailed reconciliation.

Finally, sample-size planning depends on the effect the study is intended to detect. Planning illustrations based on the observed effect show how smaller target effects call for more participants under the stated assumptions. They cannot retrospectively establish whether the completed trial was adequately designed for an effect judged clinically important, because the original design justification and clinical threshold are not reported in the registry record.

For clinical researchers, the central statistical lesson is to consider outcome definition, estimate, interval, analysis method, and reporting completeness together. A result that does not establish a difference is not a demonstration of equivalence, and secondary outcomes require caution when multiplicity handling is unclear. These distinctions matter when translating registry statistics into a disciplined account of what the study can support.

19. 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 gives limited detail about the trial's methods beyond randomization, quadruple masking, and a parallel model. It does not describe the randomization sequence, allocation concealment, identities of masked parties, or the original sample-size justification. Those details would help readers assess conduct and the rationale for the study's planned size, but are not reported in the registry record.

The primary endpoint description refers to opioid use from the first acetaminophen dose through 24 hours post-operatively, while the listed timeframe is 20 to 24 hours post-operatively. The registry does not explain how the timeframe label relates to the longer interval in the description. The available record also does not specify the regression covariates, analysis populations, missing-data method, or sensitivity analyses. These gaps limit interpretation of how the reported analysis relates to the full trial design.

The registry identifies a range of secondary outcomes, but detailed numerical summaries are not available for all of them in the record. It does not report a multiplicity strategy, a hierarchy among outcomes, or criteria for clinical importance. Without those details, secondary results are best treated as context rather than decisive evidence.

Finally, the posted summary statistics do not describe the distribution of opioid use or provide diagnostic information for the regression model. General concerns about skewness or influential values may matter for mean-based analyses, but their relevance cannot be determined from the registry summary. These are limitations of what the registry record reports, not proof that the trial's conduct or analyses were flawed.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy of IV Acetaminophen Versus Oral Acetaminophen — NCT03365622.
• Registry record last updated 2025-06-29; status last verified 2025-06.
• Results first posted 2025-06-29.
• 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.

23. Record Summary

NCT03365622 is a completed, randomized, quadruple-masked, parallel-group Phase 4 study sponsored by the University of Rochester. It compared intravenous acetaminophen with placebo pills against placebo IV plus oral acetaminophen in patients undergoing nephrectomy. The registry lists an enrollment of 214 and dates the study start to 2018-08-08 and primary completion to 2024-04-10.

The primary outcome was total opioid dose in MME through 24 hours post-operatively, including intra-operative opioids. The posted group means were 103.6 and 109.2. The registry's linear-regression analysis and the unadjusted recalculation both have 95% confidence intervals that include zero. The record also contains some numerical secondary outcomes and adverse event counts, but does not report several details needed to fully assess analysis populations, missing data, multiplicity, or the original sample-size plan.