Preoperative Acetaminophen and Carbohydrate Loading: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preoperative Acetaminophen and Carbohydrate Loading (NCT03131713), a randomized phase 3 study. The primary outcome is Maximum Pain Score.

2. Clinical Question

The study also describes ratings of pain, anxiety, thirst, hunger, and fatigue at points during the surgical visit, followed by a phone contact 48 hours after surgery to ask about maximum postoperative pain, analgesic use, and complications. This makes the timing description worth noting: the primary outcome entry says Day of surgery, while the study summary describes a 48-hour contact for maximum postoperative pain. The registry record does not make clear whether these descriptions refer to the same primary measure. The main comparison is therefore best read according to the endpoint label attached to the posted primary results, with that timing ambiguity in mind.

3. Trial Design

This was a randomized, open-label, parallel-group Phase 3 trial listed as completed. The registry record reports enrollment of 101 participants. The primary endpoint summaries include 45 participants in the control group and 51 in the intervention group; the record does not explain the difference between the enrollment figure and the endpoint group counts.

Participants were assigned to usual perioperative care or to usual care plus acetaminophen and a carbohydrate drink. The control description includes patient education about skin cancer diagnosis, treatment, and prognosis; encouragement to take food and fluids as needed; and acetaminophen on request. The intervention description adds acetaminophen 1000mg and two pouches of a commercially available carbohydrate drink at the beginning of surgery. The drink is described as containing 50gm carbohydrate in approximately 250ml total fluid.

Masking is listed as none, so the trial was not blinded according to the registry record. The study summary describes ratings during the surgical visit and a follow-up phone contact 48 hours after surgery. It says the investigators compared perioperative functional status and pain medication use between groups. The record lists several secondary outcomes, including thirst, hunger, anxiety, fatigue, postoperative analgesic use, and maximum postoperative pain.

The trial's original sample-size justification, detailed allocation procedure, and full statistical analysis plan are not reported in the registry record. The posted results identify group summaries and comparisons, but do not describe an adjusted analysis or the handling of all enrolled participants. Those gaps limit how specifically the design and analysis can be reconstructed from the public 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: No significant events during pre-assignment stage

Overall Study

Reasons for not completing this period:

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 Maximum Pain Score, measured over Day of surgery.

The registry record names Maximum Pain Score as the primary endpoint. It describes a pain scale from 0-100, with higher values indicating a worse outcome and lower values indicating a better outcome. The reported measure is a mean, with standard deviations describing variability within each group. A mean provides a compact summary of the scores, while the standard deviation indicates how dispersed individual scores were around that mean.

Pain is relevant to the stated study question because the intervention was intended to be evaluated in relation to pain and functional status around Mohs surgery. A group mean comparison can show whether the average posted score differed between the randomized groups. It does not show how every participant experienced pain, whether differences were concentrated among particular participants, or whether a difference was important to patients. The registry record does not report a threshold for a clinically meaningful difference.

There is a timing ambiguity in the record. The primary endpoint entry gives the timeframe as Day of surgery, whereas the study summary describes a phone assessment 48 hours after surgery that asks about maximum postoperative pain. The primary results should be interpreted with the stated endpoint label, but the registry record does not clearly reconcile these timing descriptions. That uncertainty is relevant to what pain period the primary comparison represents.

7. Results Posted in the Registry

• Intervention: mean 1.20 versus 2.80 on control; difference -1.60 (95% CI -1.96 to -1.24), standardized effect d = -1.84; z-test p = <0.001.

8. Secondary Efficacy Endpoints

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

Thirst

• 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:
  • Intervention: mean 10.50 versus 9.40 on control; difference 1.10 (95% CI -6.74 to 8.94), standardized effect d = 0.06; z-test p = 0.783.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intervention and the control. The interval gives the range of effects that remain compatible with the data.

Hunger

• 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:
  • Intervention: mean 17.90 versus 19.90 on control; difference -2.00 (95% CI -13.56 to 9.56), standardized effect d = -0.07; z-test p = 0.735.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intervention and the control. The interval gives the range of effects that remain compatible with the data.

Anxiety

• 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:
  • Intervention: mean 2.20 versus 7.60 on control; difference -5.40 (95% CI -10.78 to -0.02), standardized effect d = -0.42; z-test p = 0.049.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Intervention than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the question beyond the primary pain score. They include thirst, hunger, anxiety, fatigue, postoperative analgesic use, and maximum postoperative pain. Numerical summaries in the record include thirst, hunger, and anxiety. The other listed secondary outcomes are not reported in the registry record in the numerical summaries. The posted pattern is not uniform: the thirst and hunger comparisons have estimates close to zero relative to their reported uncertainty, while the anxiety comparison is in the direction of a lower score in the intervention group and has an interval just below zero at one limit.

These outcomes can provide context for the primary result, but they are not interchangeable measures. A pain score, anxiety rating, hunger rating, and medication-use outcome reflect different experiences or behaviors. The secondary results do not confirm the primary finding simply by being measured alongside it, and they do not explain why the primary scores differed. The registry record does not report a combined measure or an analysis that integrates these domains.

The secondary comparisons are unadjusted, and the record does not report a multiplicity strategy. When several outcomes are examined, the possibility of finding at least one apparently notable result by chance increases. This is particularly important when a result is near a conventional threshold. For that reason, unadjusted secondary findings are best viewed as exploratory signals rather than definitive evidence. Their interpretation should consider the estimates and confidence intervals, not only the p-values, and should avoid treating any single secondary comparison as conclusive.

The registry also does not report whether all listed secondary outcomes were prespecified in the same way, how missing observations were handled, or whether multiple time points were analyzed. Without that information, the secondary results have less inferential weight than a clearly specified primary comparison. They can still identify questions for further evaluation, but the posted registry summaries alone cannot establish a comprehensive effect across perioperative symptoms or medication use.

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

• Thirst
• Hunger
• Anxiety
• Fatigue
• Number of Participants Using Post-operative Analgesic
• Maximum Post-op Pain Score

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary result is a comparison of group means for a continuous outcome. A continuous measure can take values along a scale rather than being limited to categories. The registry describes the pain score as ranging from 0-100 and reports each group's mean and standard deviation. The mean summarizes the group's average score; the standard deviation describes how much participant scores varied around that average. A standard deviation is not the same as a confidence interval: it reflects variability among observed scores, whereas a confidence interval describes uncertainty in an estimated quantity such as a group difference.

What does the mean difference represent?

The reported mean difference is for intervention versus control. A negative value means the intervention group's average was lower under that subtraction order. Because the registry says lower pain scores represent better outcomes, the direction can be described in relation to the scale. The estimate is -1.6. This is a difference on the reported pain scale, not a relative change or a percentage. No additional transformation is described in the registry record.

How should the confidence interval be read?

A confidence interval describes a range of estimates compatible with the observed data and the method used to construct the interval. In repeated use of a valid procedure, intervals would cover the underlying quantity at the procedure's stated confidence level at the corresponding long-run rate. The primary interval is reported as -1.961 to -1.239. Its limits are both below zero, so it does not include a zero mean difference. The interval's width communicates precision: a narrower interval indicates a more precisely estimated difference, while a wider interval leaves more values plausible. The registry record does not state the confidence level or give the full method used to calculate this interval.

What does the p-value add?

The primary comparison has an unadjusted p-value of <0.001. In general, a p-value describes how unusual data at least as inconsistent with a null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The term unadjusted means this value is not described as corrected for multiple comparisons. The registry record lists no reported analyses, so details of the inferential procedure beyond the posted comparison and p-value are not available.

Why does variability matter?

The group standard deviations are 1.1 and 0.6. Variability affects how much uncertainty there is in a comparison: all else equal, more variation makes a group difference harder to estimate precisely, while more observations can improve precision. This is a general statistical principle, not an additional finding about the trial. For outcomes with over-dispersion, meaning variability substantially greater than a model expects, standard model-based uncertainty can be misleading unless the analysis accounts for it. The posted primary outcome is summarized as a mean and standard deviation, but the record does not report whether investigators assessed distributional assumptions or used any robust method.

The registry lists a randomized, parallel design and no masking. Randomization is intended to make groups comparable on average, including on characteristics not measured, but it does not guarantee identical groups in a particular trial. Lack of masking can matter for subjective ratings such as pain because participants know their group assignment. The record does not report a method that would eliminate or quantify this possibility. It also does not provide baseline group characteristics in the registry record, so no statement about their balance is possible.

There are several secondary outcomes, and their results should be treated separately from the primary result. When multiple outcomes are tested, the chance of at least one apparently unusual result can increase. A multiplicity adjustment or a prespecified hierarchy can address this, but the registry record does not report such a plan. The anxiety comparison has an unadjusted p-value of 0.049, which therefore deserves more caution than a single primary comparison considered in isolation. A p-value near a conventional threshold does not remove concerns about multiplicity, selective reporting, or imprecision.

The registry also includes planning illustrations based on observed effects. These use a two-sided significance level of 0.05, equal allocation, and a normal approximation, and show participants per arm for continuous outcomes. They are not evidence of the trial's original design rationale. The original sample-size justification and design assumptions are not reported in the registry record. The illustrations are planning tools rather than a measure of the trial's observed power.

11. Confidence Intervals and Precision

Precision is described most directly by the confidence interval around the primary mean difference. The reported estimate is -1.6, with limits of -1.961 and -1.239. The interval gives a range of values compatible with the data under the procedure used; it does not guarantee that the true difference lies within those particular limits. Its limits are both on the negative side of zero, and the registry also reports an unadjusted p-value of <0.001.

The posted primary group summaries are based on 45 control participants and 51 intervention participants. The standard deviations are 1.1 and 0.6, respectively. These values help describe the observed score distributions but do not themselves express uncertainty in the mean difference. The confidence interval is the relevant posted summary for that uncertainty. The registry record does not state the confidence level or enough method detail to independently assess the interval construction.

Statistical precision and clinical importance are different questions. An interval can be precise around a difference whose practical importance is uncertain. The record does not report a threshold for a meaningful change in pain score, nor does it describe patient preferences or a decision criterion. The primary outcome timing is also unclear because its entry says Day of surgery while the study summary describes a 48-hour postoperative phone assessment. This uncertainty affects the interpretation of what the interval estimates.

Confidence intervals for the secondary comparisons are shown in the posted tables. Intervals that include zero are compatible with both directions of a mean difference under the reported comparison; they do not establish that the groups are equivalent. Conversely, an interval that excludes zero does not by itself establish clinical importance, especially when multiple outcomes and analysis choices are involved.

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 table and curve are planning illustrations based on the observed effect, not the trial's original design calculation. For these continuous outcomes, the figures are participants per arm, rather than a total across both arms or a count of events. The general convention for time-to-event tables is different: those report the total number of events. This trial's listed primary measure is continuous.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. Rows show planning for 100%, 75%, and 50% of the observed effect. Columns show participants per arm for 80% power and participants per arm for 90% power. In plain language, power is the chance that a planned study would detect an effect of the chosen size under the assumed model and significance threshold, if that effect were present. The 90% column uses a higher chance of detection than the 80% column and therefore calls for more participants in the planning illustration.

Smaller effects are harder to distinguish from random variation, so detecting a smaller effect generally requires more participants. The table illustrates that planning relationship using the observed estimate as its reference; it does not show the number of participants needed for a clinically meaningful effect unless that effect is the one being represented. This is not observed power. The trial's own sample-size assumptions and justification are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.600; pooled standard deviation σ = 0.871.
2. n = 2 × (1.96 + 0.842)² × 0.871² / -1.600² = 4.6, rounded up to 5 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.6                      # observed difference in means
sigma <- 0.870558636982904                     # 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(3131713)
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 = 5 (80% power), 7 (90% power)
 75% of observed effect: n per arm = 9 (80% power), 12 (90% power)
 50% of observed effect: n per arm = 19 (80% power), 25 (90% power)
power.t.test: 5.8 
Simulated power at n = 5 per arm: 0.723 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and several secondary outcomes, but it does not report a multiplicity adjustment, testing hierarchy, or other strategy for controlling the interpretation of multiple comparisons. Multiplicity arises when several hypotheses are tested: even if no underlying differences exist, one or more results may appear unusual by chance. This does not make every secondary result uninformative, but it means unadjusted p-values should not be read as if each were the only test conducted.

The record lists no reported analyses. It therefore does not provide a full statistical analysis plan, including whether the primary comparison was prespecified in the form posted, how repeated ratings were handled, or whether any covariates or subgroup analyses were planned. The trial's original sample-size justification and any planned interim analyses are not reported in the registry record. No interim analysis should be inferred from the completed status or from the posted results.

Missing-data information is also not reported in the registry record. The primary summaries include 45 control participants and 51 intervention participants, while overall enrollment is listed as 101. The record does not explain the difference, identify missing primary scores, or describe imputation or other handling of incomplete observations. It is therefore not possible to determine from these summaries whether the primary analysis included all randomized participants or a subset. The analysis population and any exclusions are not reported.

These omissions affect interpretation rather than changing the arithmetic of the posted summaries. A complete account would clarify which participants contributed to each outcome, how incomplete data were treated, and whether the analysis followed a prespecified plan. Without those details, the posted p-values and intervals can be described, but their relationship to the full trial design and all analyses cannot be fully evaluated.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry record reports zero serious adverse events among the 45 control participants at risk and zero among the 51 intervention participants at risk. It also reports zero other adverse events in each group and zero deaths in both groups. These figures describe what was posted for the groups and at-risk counts shown in the safety record.

A zero count in a trial does not prove that an event cannot occur or that the intervention has no safety risks. The record does not provide detailed event definitions, a safety follow-up timeframe, or information about how events were collected and adjudicated. It also does not report additional safety analyses in the registry record. These limitations matter when interpreting the absence of reported events, especially when the number of participants is limited.

Accordingly, the appropriate reading is that no serious or other adverse events and no deaths were reported in the listed groups in this registry record. This is a description of the posted safety data, not a comparative safety conclusion.

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

The posted primary comparison is a difference in average pain scores between randomized groups. It shows a lower mean score in the intervention group, and the confidence interval for the mean difference is entirely below zero. The scale description indicates that lower scores represent better outcomes. These findings describe the posted data and their statistical uncertainty; they do not, on their own, establish how participants experienced the intervention or whether any difference was important to them.

The registry record does not report a threshold for clinical importance. Statistical evidence against a zero difference and clinical importance are distinct: the first concerns how compatible the observed data are with a null comparison under an analysis, while the second requires context about patient experience and meaningful change. The posted record also leaves uncertainty about timing, because the primary outcome entry names the day of surgery and the summary describes a postoperative phone assessment at 48 hours.

The trial tested a package added to usual care: acetaminophen and a carbohydrate drink, alongside the usual care described for the intervention group. The registry results do not isolate the contribution of either component. The open-label design also means participants knew their assignment, which can matter for subjective self-reported outcomes. The record does not quantify the effect of this feature.

The results should not be generalized beyond the population and setting described without additional evidence. The registry record concerns patients undergoing Mohs micrographic surgery for non-melanoma skin cancers. It does not establish what would happen in other procedures, populations, or care settings. Nor do the posted summaries establish effects on all outcomes listed in the study description, since several secondary outcomes are not numerically.

In short, the record reports a lower average primary pain score for the intervention group, with a confidence interval that excludes zero. The available information does not settle clinical importance, the exact time period represented by the primary measure, completeness of follow-up, or the robustness of conclusions across multiple outcomes and analysis choices.

17. Why This Trial Matters Statistically

This trial illustrates why a statistically notable result should be read alongside its endpoint definition, scale, uncertainty, and design. The primary estimate is a mean difference on a pain scale, and its confidence interval conveys more about precision than the p-value alone. The scale's direction also matters: here, lower scores are described as better, so the sign of the estimate has a clear descriptive interpretation.

It also shows how registry records can leave important interpretive details unresolved. The primary endpoint is labeled Day of surgery, while the study summary describes a 48-hour postoperative assessment of maximum pain. The public record does not reconcile these descriptions. A reader can report the posted result accurately while still recognizing that the target time period is uncertain.

The secondary outcomes highlight the role of multiplicity. Several symptoms and behaviors were considered, but the record does not report a correction strategy or detailed analysis plan. An unadjusted secondary p-value should therefore carry less weight than a clearly prespecified primary comparison. This is not a reason to ignore secondary outcomes; it is a reason to interpret them in context and avoid overclaiming.

Finally, the planning illustrations offer a useful distinction between designing a future study and assessing the one completed. The sample-size rows use the observed effect and stated planning assumptions. They can show how smaller target effects require more participants, but they cannot recover the trial's original planning rationale. Keeping those uses separate helps prevent planning figures from being mistaken for evidence about observed power or proof of the result.

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 affect interpretation. First, the timing of the primary measure is ambiguous: the endpoint entry gives Day of surgery, while the study summary describes a phone assessment 48 hours after surgery for maximum postoperative pain. The registry record does not clarify whether these refer to the same outcome assessment.

Second, the primary endpoint summaries include 45 control and 51 intervention participants, while total enrollment is 101. The record does not explain the difference or report how many participants were randomized, analyzed, or missing data for each outcome. Missing-data methods and the analysis population are not reported in the registry record.

Third, the trial is open-label and includes subjective ratings. Knowledge of assignment may influence self-reported outcomes, but the registry does not quantify or address this possibility. The intervention also combines acetaminophen with a carbohydrate drink, so the posted comparison cannot distinguish their separate contributions.

Fourth, no clinical-importance threshold, full statistical analysis plan, multiplicity procedure, or original sample-size justification is reported in the registry record. The posted secondary results are unadjusted, and numerical summaries for all listed secondary outcomes are not available. The record also does not provide enough information to assess baseline balance, protocol deviations, or the completeness of safety and follow-up ascertainment.

These limitations do not invalidate the posted group summaries. They constrain what can be concluded from them and identify details that a full report would need to clarify.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Preoperative Acetaminophen and Carbohydrate Loading — NCT03131713.
• Registry record last updated 2019-10-07; status last verified 2019-10.
• Results first posted 2019-10-07.
• 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

This completed, randomized, open-label, parallel-group Phase 3 trial compared usual perioperative care with usual care plus acetaminophen 1000mg and a carbohydrate drink in patients undergoing Mohs micrographic surgery for non-melanoma skin cancers. The registry reports enrollment of 101 participants.

The primary endpoint is Maximum Pain Score, described on a 0-100 scale with higher scores indicating worse outcomes. The posted means are 2.8 for control and 1.2 for intervention, with a mean difference of -1.6 and a confidence interval from -1.961 to -1.239. The unadjusted p-value is <0.001.

The record also lists secondary outcomes and reports zero serious adverse events, other adverse events, and deaths in both groups. The primary outcome timing, missing-data handling, analysis population, multiplicity plan, and original sample-size justification are not reported clearly in the registry record.