Effect IV Ibuprofen and Inflammatory Responses: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect IV Ibuprofen and Inflammatory Responses (NCT01938040), a randomized phase 4 study. The primary outcome is Stress Response Inflammation Markers :Cortisol and C Reactive Protein (CRP).

2. Clinical Question

The clinical question is about postoperative inflammatory-response measurements and their relation to recovery, rather than a single reported clinical recovery outcome. The study summary says investigators sought to study ways to improve recovery after surgery and describes inflammation as part of the body's response to injury. It also notes that participants were asked to complete questionnaires and that blood samples were collected, including samples while patients were under anesthesia.

Several secondary outcomes are listed, including IL-6, IL-10, quality of recovery, fatigue, cognitive recovery, and geriatric depression measures. The registry record does not report numerical results for these outcomes in the information available for this analysis. It therefore does not establish what differences, if any, were observed in inflammatory markers, recovery measures, or questionnaire outcomes.

3. Trial Design

The registry identifies this as a completed, randomized, parallel-group, phase 4 pilot study. Enrollment is listed as 60. Participants were assigned to intravenous ibuprofen or placebo. The ibuprofen arm is described as receiving 800mg in 100cc of normal saline over 5 minutes; the placebo arm is described as receiving 100mL of normal saline over 5 minutes.

The registry's masking field says triple masking, while the official study title describes the study as double blind. These descriptions are both present in the record; it does not explain the difference or identify which roles were masked. Allocation concealment procedures, the method used to generate the random sequence, and whether assignment was stratified are not reported in the registry record.

The study is listed as having started in 2013-05, with primary completion in 2014-08 and an overall status of completed. The sponsor is listed as University of Medicine and Dentistry of New Jersey. These registry entries describe the study record and do not, by themselves, establish when analyses were completed or results were made available.

The primary outcome concerns serum cortisol and CRP at 2 hours following the end of surgery, with the description also noting preoperative and intraoperative measurements. The registry lists 11 outcome measures and one analysis, but does not give a complete analysis population, a participant flow, or outcome-specific denominators. It also does not report protocol details such as the planned treatment contrast or a sample-size justification. The sample-size material associated with the record is described as a planning illustration based on an observed effect, not as the original trial design rationale.

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: Of the 60 patients randomized 5 did not receive study medication. The surgical case was either cancelled or the subjects withdrew consent.

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 Stress Response Inflammation Markers :Cortisol and C Reactive Protein (CRP), measured over 2 hours following end of surgery.

The primary outcome is titled “Stress Response Inflammation Markers: Cortisol and C Reactive Protein (CRP).” It describes serum concentrations drawn in the Post Anesthesia Care unit at 2 hours following surgery and compared with measurements taken preoperatively and intraoperatively. The record gives pg/mL as the unit and identifies the measure as a mean with standard deviation.

Cortisol and CRP are presented in the registry as markers related to stress response and inflammation. In general, repeated measurements can describe how a marker varies across the perioperative period, while a comparison between randomized groups can assess whether their observed measurement patterns differ. The stated postoperative time point situates the measurement after the operation; the earlier measurements provide context for the perioperative course. The registry does not describe a single prespecified summary such as a change score, a treatment-by-time contrast, or an area-under-the-curve measure.

The primary outcome description includes more than one marker and more than one measurement occasion. The posted record does not reduce these categories and time points to one comparison. Accordingly, the primary endpoint can be described from the registry's measurement plan, but a numerical estimate, uncertainty interval, or test result for it is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized and parallel-group. In a randomized study, assignment is intended to make treatment groups comparable on average with respect to factors that could affect outcomes. Randomization does not guarantee identical groups, particularly in a pilot study, and the registry does not report the sequence-generation or allocation-concealment procedures. The parallel-group description means participants were assigned to a treatment group rather than described as crossing between treatments.

What does masking mean in this record?

Masking is intended to limit the influence of knowledge about assigned treatment on participant experiences, clinical care, or outcome assessment. The registry field identifies triple masking, whereas the official title calls the study double blind. The record does not define which people were masked, or explain the wording difference. It is therefore appropriate to report both registry descriptions without inferring who knew treatment assignments.

How should the primary measurements be understood?

The primary measure is continuous: the registry specifies means and standard deviations for serum cortisol and CRP, with pg/mL as the unit. A mean describes the arithmetic average, while a standard deviation describes the spread of individual measurements around that average. These are different quantities: the standard deviation is not the uncertainty of the mean or of a treatment-group difference.

Measurements are described at preoperative and intraoperative occasions and at 2 hours following the end of surgery. Repeated observations from the same person are generally related rather than independent. In general, an analysis of repeated measurements needs to account for that within-person relationship if it uses multiple observations together. The registry does not report whether its analysis used a repeated-measures model, separate comparisons at each time point, a change-from-baseline approach, or another method. It also does not specify how cortisol and CRP were combined or treated as separate primary measures.

What do confidence intervals and p-values contribute?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. Its width reflects precision: narrower intervals indicate greater precision, while wider intervals indicate less precision. A p-value describes how compatible the observed data are with a specified null hypothesis under a statistical model; it does not measure the size or clinical importance of an effect. Neither an interval nor a p-value for a reduced primary treatment comparison is reported in the registry record, so those measures cannot be interpreted for the primary outcome.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, its standard errors and uncertainty intervals can be too small, and tests can appear more decisive than warranted. The registry identifies continuous outcomes summarized by means and standard deviations, but does not report a model or an assessment of over-dispersion. This concept is therefore general context, not a finding about this trial.

What do the planning assumptions mean?

The record describes planning illustrations calculated from the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, these illustrations are expressed as participants per arm for 80% power or another stated power level. These are planning scenarios, not observed participant counts, and not observed power. They are also not evidence that the trial was designed with those assumptions. The original sample-size rationale is not reported in the registry record.

In general, a planning calculation estimates the number of participants needed to detect a specified effect under stated assumptions. It depends on the effect size, variability, significance level, allocation, and the chosen power target. Because the planning scenarios are based on an observed effect, their interpretation is conditional on that estimate and its uncertainty; the calculation does not establish that the effect is real or clinically important.

What can be inferred from the analysis count?

The record lists one analysis and 11 outcome measures. Those entries do not identify the analysis method or clarify whether the single listed analysis includes multiple outcomes, time points, or treatment contrasts. No model specification, adjustment set, handling of repeated measures, or multiplicity procedure is reported in the registry record. General methodological considerations can explain what such choices mean, but they cannot establish which choices were made in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary cortisol and CRP outcome and secondary measures of IL-6, quality of recovery, fatigue, IL-10, cognitive recovery, and geriatric depression. When several outcomes, markers, or time points are examined, the chance of obtaining at least one apparently notable result can increase if all are tested without an adjustment. In general, multiplicity procedures can control this risk, but they may also change the precision or power of individual comparisons. The registry record does not report whether any multiplicity adjustment was planned or used.

The primary outcome itself includes multiple markers and time points. The posted record does not reduce these to one comparison, and it does not describe a hierarchy or identify a single primary contrast among them. The listing of one analysis does not clarify how many statistical tests or estimates were generated.

Missing-data methods and outcome-specific missingness are not reported in the registry record. It does not give the number of participants with usable measurements at each time point, reasons for missing measurements, or whether missing values were imputed. The analysis population is also not reported: the record does not say whether the primary analysis included all randomized participants, only participants who received treatment, or a different set.

These omissions limit assessment of both bias and precision. In general, conclusions can depend on why observations are missing and how the analysis handles them. Without a participant flow, denominators by outcome and time point, or an analysis description, the available record does not permit evaluation of those choices.

11. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: patient unable to be extubated at the end of the surgical procedure (3.6%).

The registry's adverse-event summaries list 28 participants at risk in the Caldolor/Ibuprofen group and 27 at risk in the placebo group. One serious adverse event is listed for the ibuprofen group and none for placebo. Other adverse events are listed as zero in both groups. Deaths are recorded as null for both groups; null should not be read as a reported count of zero.

The serious adverse-event term listed among the most frequent terms is “patient unable to be extubated at the end of the surgical procedure,” with 3.6%. The registry record does not explicitly connect that term to a specific group or explain how it relates to the serious-event group counts. It should therefore be reported as a listed term rather than assigned to an arm by assumption.

These figures are counts in the registry safety summary, not estimates of comparative risk. The record does not provide event-level narratives, timing, duration, severity beyond the serious-event classification, or a statistical comparison. Nor does it explain the denominators in relation to the total enrollment. A small number of recorded events cannot, by itself, establish whether groups differ in safety. The registry record does not report further detail needed to characterize or compare the events.

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

The record documents a randomized pilot comparison of intravenous ibuprofen with saline placebo in patients undergoing surgery with general anesthesia. It gives the treatment descriptions and identifies cortisol and CRP measurements at perioperative time points, including 2 hours after the end of surgery. It also lists recovery-related and other secondary outcomes. These details show what the study set out to examine, but they are not themselves evidence of an observed treatment difference.

The registry does not report a single reduced comparison for the primary endpoint, or the numerical group results, effect estimate, confidence interval, or p-value needed to judge its magnitude and precision. It therefore does not establish from the posted results whether the groups had different cortisol or CRP measurements. The same limitation applies to the listed secondary outcomes for which numerical results are not reported in the record.

The design and enrollment do not compensate for absent outcome estimates. Randomization is a design feature; it does not reveal the result. Likewise, the sample-size illustrations are planning calculations based on an observed effect, not observed power and not a report of the trial's original rationale. The safety counts are descriptive registry entries and do not answer the primary inflammation question.

In general, a clinical trial result is best interpreted using the estimated treatment contrast and its uncertainty, together with the outcome definition, analysis population, missing-data handling, and study limitations. Those elements are not reported in sufficient detail for a quantitative interpretation of the primary outcome. No claim about benefit, lack of benefit, or clinical importance follows from the record's design description alone.

The appropriate reading is therefore limited: the registry records the study question, assigned interventions, planned measurements, and some safety counts, while leaving the primary numerical comparison unreported. Any stronger conclusion would require results and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates a key distinction between a trial's design and the evidence available for interpreting its outcome. Randomization, a placebo comparator, and defined blood-sampling times describe how a comparison was intended to be made. They do not provide the estimated difference between groups. For statistical interpretation, the outcome summaries and their uncertainty are essential.

The primary outcome combines cortisol and CRP with multiple measurement occasions. Such an endpoint raises practical questions about what contrast is most relevant: a value at a particular time, change from an earlier measurement, or a pattern across time. In general, these choices affect the estimand—the quantity a statistical analysis aims to estimate. The registry does not identify a single reduced comparison, so a reader cannot determine which treatment contrast should anchor interpretation.

The record also makes clear why study size and analysis details matter. Enrollment is listed as 60, but outcome-specific denominators and the sample-size rationale are not reported. Planning illustrations based on an observed effect cannot be read as prospective justification or proof of adequate precision. A pilot designation likewise does not supply a statistical plan.

Finally, the registry lists 11 outcome measures, while the record does not describe how multiplicity was handled or how missing observations were treated. These are not technical details separate from interpretation: they affect how much confidence to place in reported estimates and how broadly findings can be generalized. Here, the lack of a numerical primary comparison is the central constraint. The record is informative about the intended clinical question, but not sufficient to quantify the primary outcome result.

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 record does not report the primary outcome as one reduced comparison, and does not give group means, standard deviations, treatment-effect estimates, confidence intervals, or p-values for cortisol and CRP. It also does not state whether the markers were analyzed separately or how the several measurement occasions were handled. This prevents assessment of the direction, magnitude, and precision of the primary result.

Participant eligibility criteria and baseline characteristics are not reported in the record. Although enrollment is listed as 60, the safety summaries give different at-risk counts by group, and a complete participant flow or outcome-specific denominators are not reported. The record does not explain these figures or indicate how many participants contributed usable measurements at each time point.

Important design and analysis details are also absent. Random-sequence generation, allocation concealment, the roles included in masking, the statistical model, covariate adjustment, analysis population, missing-data methods, and multiplicity handling are not reported in the registry record. The masking field and official title use different descriptions, without an explanation of the difference.

The registry identifies the study as a pilot and lists a planning illustration based on an observed effect, but the original sample-size justification is not reported. The adverse-event summary offers limited detail and does not explain the relationship between its serious-event term and group-specific counts. These limitations concern what the record allows a reader to assess; they do not establish that any particular design or analysis choice was made.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect IV Ibuprofen and Inflammatory Responses — NCT01938040.
• Registry record last updated 2016-12-21; status last verified 2016-10.
• Results first posted 2016-12-21.
• 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.

18. Record Summary

The registry record describes a completed, randomized, parallel-group phase 4 pilot study with enrollment of 60. Participants were assigned to intravenous ibuprofen, described as 800mg in 100cc of normal saline over 5 minutes, or saline placebo, described as 100mL over 5 minutes. The primary outcome concerns serum cortisol and CRP, with measurements described preoperatively, intraoperatively, and at 2 hours following the end of surgery.

The record lists 11 outcome measures and one analysis. It does not report a single reduced primary-outcome comparison or the numerical results needed to assess its magnitude and precision. Several analysis details, including missing-data handling, analysis populations, and multiplicity procedures, are not reported in the registry record. Safety entries list one serious adverse event in the ibuprofen group and none in the placebo group, with at-risk counts of 28 and 27, respectively; further interpretation is limited by the lack of additional event and denominator detail.