This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effect of IV Acetaminophen on Patients in the Neurocritical Care Unit (NCT01948505), a randomized phase 4 study. The primary outcome is Narcotic Requirement After Surgery.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01948505 |
| Phase | Phase 4 |
| Condition | Post-operative Craniotomy Patients, Carotid Endarterectomy and Carotid Artery Stenosis Patients, Post-op Spine Patients Admitted to the NCCU |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 210 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
The registry lists post-operative craniotomy patients; carotid endarterectomy and carotid artery stenosis patients; post-operative spine patients admitted to the neurocritical care unit; endovascular patients undergoing intracranial intervention; and traumatic brain injury patients who were not taking anything by mouth for at least 12 hours. The primary endpoint description specifically refers to narcotic consumption after craniotomy. The record does not clarify how the listed populations relate to the patients included in that primary analysis.
Intervention
Patients in the experimental group received intravenous acetaminophen, scheduled at 1000mg intravenously every 8 hours, until they could tolerate oral intake and the intravenous line was saline-locked, or until 48 hours on medication had elapsed.
Comparator
The placebo group received intravenous normal saline, scheduled at 100ml intravenously every 8 hours, with the same stated stopping conditions: tolerating oral intake and intravenous saline-lock, or reaching 48 hours on medication.
Primary question
The primary question was whether patients receiving intravenous acetaminophen in addition to the standardized pain protocol had a lower mean narcotic requirement during the first 48 hours after craniotomy than patients receiving placebo. Narcotic use was converted to oral morphine equivalents for the endpoint. The registry narrative says the acetaminophen group did not have a statistically significantly lower mean requirement.
3. Trial Design
The registry describes a phase 4, randomized, triple-masked, parallel-group trial sponsored by the University of Utah. The listed status is completed. The study start is recorded as 2013-08 and primary completion as 2016-11. Enrollment is recorded as 210. The record does not state the allocation ratio or explain the sequence-generation and concealment procedures.
The experimental intervention was scheduled intravenous acetaminophen at 1000mg every 8 hours. The comparator was scheduled intravenous normal saline at 100ml every 8 hours. Both regimens were to continue until the patient could tolerate oral intake and the intravenous line was saline-locked, or until 48 hours on medication had elapsed. The record describes the acetaminophen as being given in addition to a standardized pain protocol, but further details of that protocol are not reported in the registry record.
Although the registry lists several neurocritical care populations, the primary endpoint description is specifically framed around narcotic consumption during the first 48 hours after craniotomy. The record does not explain whether the primary analysis included only craniotomy patients or how the other listed populations were represented in that analysis. That distinction matters when interpreting how directly the primary result applies across the listed clinical groups.
For the primary endpoint, the posted arm estimates each have a reported sample size of 102. The registry separately reports safety counts for groups with 105 at risk. These figures refer to different posted result categories and should not be treated as interchangeable. The analysis population definitions, reasons for any difference between those counts, and participant flow by arm are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Experimental Group | Placebo Group |
|---|---|---|
| STARTED | 105 | 105 |
| COMPLETED | 105 | 105 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Experimental Group | Placebo Group | Total |
|---|---|---|---|---|
| Participants analysed | 102 | 102 | 204 | |
| Age, Continuous | years | 50.6 (47.6 to 53.5) | 50.3 (47.4 to 53.2) | 50.5 (47.5 to 53.3) |
| Sex: Female, Male: Female | Participants | 71 | 54 | 125 |
| Sex: Female, Male: Male | Participants | 31 | 48 | 79 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Narcotic Requirement After Surgery, measured over 48 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Morphine Equivalents |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean narcotic requirement during the first 48 hours after surgery, expressed in morphine equivalents. The registry description says narcotic use was converted into oral morphine equivalents and totaled for each postoperative day. Expressing different narcotic medications on a common morphine-equivalent scale provides a way to summarize their use with one continuous measure.
This endpoint is used to assess narcotic consumption in the context of the trial’s pain-control question. It is a measure of medication use, not a direct measure of pain intensity, sedation, or patient experience. The registry’s brief summary also mentions assessing pain, sedation levels, and common side effects, but the posted primary result is narcotic requirement. Results for other outcomes are not reported in the registry record.
The posted primary estimates are means with 95% confidence intervals. The experimental group mean is 123.5 morphine equivalents, with a 95% confidence interval from 102.9 to 144.2. The placebo group mean is 134.2, with a 95% confidence interval from 112.1 to 156.3. The record gives the endpoint timeframe as 48 hours. The registry narrative says the experimental group did not have a statistically significantly lower mean narcotic requirement than the placebo group.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results report mean narcotic requirements of 123.5 morphine equivalents in the experimental group and 134.2 in the placebo group. The corresponding 95% confidence intervals are 102.9 to 144.2 and 112.1 to 156.3. These are group-level estimates of narcotic use during the stated 48-hour timeframe, not individual patient outcomes.
The registry narrative states that the experimental group did not have a statistically significantly lower mean requirement than the placebo group. The record does not provide a p-value, a confidence interval for the between-group contrast, or an adjusted estimate. It is therefore not possible to state from the posted results how compatible the data are with particular values for the treatment contrast. Nor should the two arm-specific confidence intervals be substituted for a confidence interval of the difference between arms.
A confidence interval describes uncertainty around an estimated mean under the statistical model used to calculate it. It is not a range containing every participant’s outcome, and it does not mean that each value within the interval is equally likely. The posted intervals convey uncertainty for each group mean; they do not, on their own, establish the precision of the contrast that answers the comparative question.
The registry gives a negative statement about statistical significance, but does not report the statistical test, model, or adjustment strategy behind that statement. The posted results therefore support a bounded interpretation: the registry reports no statistically significant lower mean narcotic requirement for the acetaminophen group, while the numerical arm means and their uncertainty should be read as estimates rather than definitive evidence about the contrast. No claim about pain relief, sedation, or other benefits follows from this primary endpoint alone.
Enrollment is recorded as 210, while the primary endpoint estimates are each accompanied by a group sample size of 102. The registry does not explain the analysis population or the relationship between enrollment and the endpoint counts. Without information on exclusions, missing outcome data, and analysis procedures, the reason for that distinction and its implications cannot be determined from the registry record.
9. Statistical Methods Explained
The primary outcome is continuous: it is a mean amount of narcotic use expressed in morphine equivalents. For a continuous outcome, a group mean summarizes the average level of the measured quantity among the participants included in that group’s analysis. It does not describe the full distribution, so it does not show whether individual values were tightly clustered or widely spread.
What do the confidence intervals describe?
The registry reports a 95% confidence interval for each arm mean. In general, a confidence interval conveys the statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision than a wider interval for the same quantity. The intervals concern the separate group means; the main comparative question concerns the difference between groups. A direct interval for that contrast is not reported in the registry record.
Confidence intervals should not be interpreted as individual ranges or as a guarantee that the true value lies within the displayed endpoints. Their long-run interpretation depends on the method and assumptions used to construct them. The registry identifies the interval level but does not describe the calculation method, distributional assumptions, or any adjustment used for the primary analysis.
Why is the comparison more than a comparison of two means?
The scientific question is comparative: whether mean narcotic requirement differed between the randomized groups. A valid estimate of that contrast depends on how the endpoint was analyzed, which participants were included, and how any unavailable measurements were handled. The two reported means are useful descriptive estimates, but they do not reveal the exact contrast estimate or its uncertainty. The registry narrative reports that the experimental group did not have a statistically significantly lower mean requirement; the underlying test statistic and p-value are not reported in the registry record.
Random allocation is intended, in general, to support a fair comparison by reducing systematic differences between groups at assignment. It does not ensure that every later analysis is free of bias. The interpretation also depends on adherence to the assigned regimen, outcome measurement, follow-up, and the analysis population. Details about these matters are not reported in the registry record.
What does statistical significance tell readers?
In general, a statistical significance test evaluates how compatible observed data are with a specified null hypothesis under a statistical model. A finding that is not statistically significant does not establish that the groups are identical, nor does it establish that a clinically meaningful difference is impossible. It means the stated analysis did not meet its criterion for statistical significance. The registry does not report the significance threshold, the test, or the exact p-value, so those details cannot be assessed.
Statistical significance also does not measure the clinical importance of an effect. Clinical interpretation would require context about what change in morphine equivalents would matter, as well as attention to the uncertainty around the between-group estimate. A threshold for a clinically important difference is not reported in the registry record.
How should planning illustrations be understood?
Sample-size illustrations based on an observed effect are planning calculations, not evidence that the completed trial had a particular probability of detecting an effect. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations are conditional on those assumptions and on the chosen target effect. They are not the trial’s observed power and do not change the interpretation of the posted result.
The registry does not report its original sample-size justification or statistical analysis plan. It also does not report whether the analysis used an adjusted model, whether there were interim analyses, or how the reported confidence intervals were derived. Those omissions limit independent assessment of the statistical procedure and its relationship to the study design.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures and reports no secondary results. The primary result described is narcotic requirement after surgery; results for the other outcome measure are not reported in the registry record. The registry does not report a multiplicity adjustment, a hierarchy of outcomes, or a plan for interpreting multiple tests. Without those details, readers cannot assess whether or how the possibility of multiple comparisons was addressed.
Handling of missing primary outcome data is also not reported in the registry record. The endpoint estimates are each accompanied by a group sample size of 102, while overall enrollment is recorded as 210. The registry does not state whether the difference reflects missing measurements, eligibility for the analysis, exclusions, or another reason. It does not report imputation methods, sensitivity analyses, or participant-level flow through the analysis.
The record does not specify whether the primary analysis followed an intention-to-treat approach, included only participants who received treatment, or used another analysis population. It also does not give details on adherence, withdrawals, or how participants who stopped the assigned regimen were handled. These omissions matter because analysis choices can affect the interpretation of a randomized comparison, especially when outcomes are unavailable or treatment exposure differs from assignment.
Details about covariate adjustment, subgroup analyses, and any interim monitoring are not reported in the registry record. The absence of those details does not establish that such procedures were or were not used; it means they cannot be evaluated from the posted information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Experimental Group | 0 | 105 | 0.0% |
| Placebo Group | 0 | 105 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Experimental Group | 0 of 105 |
| Placebo Group | 0 of 105 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Experimental Group | 0 of 105 |
| Placebo Group | 0 of 105 |
The registry reports zero serious adverse events among 105 participants at risk in the experimental group and zero among 105 at risk in the placebo group. It also reports zero other adverse events in each group, with 105 at risk in each. Deaths are recorded as zero in both groups. No serious adverse event terms are listed.
These figures are counts within the safety groups recorded in the registry. They do not establish that no adverse events occurred outside the categories or observation period captured by the record, and zero reported events do not prove that an event is impossible. The registry does not report event definitions, surveillance procedures, timing, severity criteria, or the method used to determine whether events were related to treatment.
The safety counts have a reported at-risk number of 105 per group, whereas the primary outcome estimates each have a reported sample size of 102. The registry does not explain this difference. Safety findings should therefore be read using their own reported denominators rather than assumed to share the primary outcome analysis population. These counts alone do not support a broad comparison of safety between treatments.
12. What the Result Does, and Does Not, Mean
The posted primary result is a comparison of mean narcotic requirement, expressed in morphine equivalents, during the first 48 hours after surgery. The experimental group mean is 123.5 and the placebo group mean is 134.2. The registry narrative states that the experimental group did not have a statistically significantly lower mean requirement. This describes the reported analysis; it does not show that the groups had identical outcomes.
The result does not establish whether any difference between the groups would be clinically important. The record does not give a threshold for a meaningful change, a direct confidence interval for the between-group contrast, or a p-value. The arm-specific confidence intervals describe uncertainty in the group means, not the range of possible individual outcomes or the uncertainty of the contrast itself.
The endpoint measures narcotic use, not pain intensity, sedation, or patient satisfaction. Although the registry’s brief summary identifies pain, sedation, and common side effects as topics of interest, secondary results are not reported in the registry record. No conclusion about those outcomes can be drawn from the primary endpoint estimate.
The trial’s listed patient groups span several neurocritical care settings, while the primary endpoint description refers to patients after craniotomy. The registry does not clarify which listed populations contributed to the primary analysis or how representative that analysis was of the broader set of groups. The applicability of the primary result across those settings therefore cannot be determined from the posted information.
Finally, the registry record does not provide the full analysis plan, details of missing data, or the analysis population definition. These limitations do not negate the reported estimates, but they constrain how fully their precision, robustness, and scope can be assessed.
13. Why This Trial Matters Statistically
This trial illustrates why the endpoint and the treatment question need to be read together. The primary measure is mean narcotic consumption converted into morphine equivalents, while the broader stated interests include pain, sedation, and side effects. Medication use is a distinct outcome from those other measures. A result on narcotic requirement alone cannot substitute for evidence about pain intensity or sedation.
It also highlights the difference between an arm-specific estimate and a direct treatment contrast. The registry reports a mean and confidence interval for each group and states that the experimental group did not have a statistically significantly lower mean requirement. The comparative estimate and its uncertainty are not posted. This makes it important to distinguish the descriptive summaries from the statistical test underlying the narrative conclusion.
The record also shows why analysis populations and denominators matter. Enrollment is listed as 210, primary endpoint estimates have a reported sample size of 102 in each group, and safety groups have 105 at risk in each group. Those figures are reported for different parts of the results, and the registry does not explain their relationship. Clear reporting of participant flow and analysis populations helps readers understand who contributed to each estimate.
Finally, a completed randomized trial can still leave key statistical details unavailable in its registry record. Information about missing data, multiplicity, the analysis model, and the original sample-size rationale is not reported. Recognizing these boundaries is part of interpreting trial results carefully: a numerical estimate can be described precisely while the evidence remains limited in what it establishes.
14. 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 does not report the statistical analysis plan, the method used to calculate the confidence intervals, the comparative effect estimate, or the p-value. The narrative conclusion states that the experimental group did not have a statistically significantly lower mean narcotic requirement, but the analysis details supporting that statement are not available in the registry record.
The primary endpoint description focuses on patients after craniotomy, while the listed conditions include several other neurocritical care populations. The record does not specify which populations were included in the primary analysis, how they were distributed across groups, or whether the result was intended to represent all listed conditions. This limits assessment of the result’s scope.
Participant flow, missing outcome data, and analysis population definitions are not reported. The primary endpoint groups each have a reported sample size of 102, while safety groups report 105 at risk. The reason for these different counts is not stated. The record also does not describe adherence, discontinuation, or treatment exposure after randomization.
The registry gives no detailed description of the standardized pain protocol, the endpoint measurement process, or the methods for assessing safety outcomes. It does not report a clinically important difference for narcotic requirement, secondary outcome results, or multiplicity procedures. These gaps restrict assessment of clinical importance, robustness, and the completeness of the evidence available in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of IV Acetaminophen on Patients in the Neurocritical Care Unit — NCT01948505.
- Registry record last updated 2023-04-24; status last verified 2018-05.
- Results first posted 2023-04-24.
- 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.
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18. Record Summary
This completed, randomized, triple-masked, parallel-group phase 4 trial compared scheduled intravenous acetaminophen with intravenous normal saline in neurocritical care patients. The registry lists enrollment of 210 and records the study start as 2013-08 and primary completion as 2016-11.
The primary endpoint was mean narcotic requirement during the first 48 hours after surgery, expressed in morphine equivalents. The experimental group mean was 123.5, with a 95% confidence interval from 102.9 to 144.2; the placebo group mean was 134.2, with a 95% confidence interval from 112.1 to 156.3. The registry narrative says the experimental group did not have a statistically significantly lower mean requirement.
Secondary results, analysis details, missing-data procedures, and the relationship between the reported primary and safety group counts are not reported in the registry record. Safety counts record zero serious adverse events, zero other adverse events, and zero deaths in both groups.