Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage (NCT01530880), a randomized phase 4 study. The primary outcome is Prevalence of Fever Burden.

2. Clinical Question

The registry frames the study as a comparison of fever control after non-traumatic brain hemorrhage. Its stated rationale is that fever is common after head injury and is associated with poor recovery. The record also describes limitations of body cooling as a fever-control approach, including shivering and the use of sedating drugs to control it. Those statements explain the motivation for studying a drug-based strategy; they are not results from this trial.

The primary outcome was intended to quantify fever burden during treatment, rather than recovery after brain injury. The registry describes a future larger study of recovery as a possible next step if the initial study showed a favorable result. Such recovery effects were not the reported primary question for this trial. The registry record does not report a comparative estimate of fever burden, so it does not establish how the two assigned strategies compared on that measure.

3. Trial Design

This was a phase 4, randomized, parallel-group study with no masking. Columbia University is listed as the sponsor. The registry records a start date of 2012-10, primary completion on 2016-03-17, enrollment of 35, and status of terminated. The reason for termination is not reported in the registry record.

Participants were assigned to intravenous ibuprofen or oral acetaminophen. The ibuprofen regimen began with a 400 mg intravenous bolus over 30 minutes and continued with an infusion at 85 mg/hr. The standard-of-care arm used oral acetaminophen at 650 mg, then 650 mg every 6 hours as needed to maintain temperature < 38.3 C (100.9 F). The record does not report the randomization method, allocation ratio, concealment procedures, or the criteria used to determine when treatment began or ended.

The primary outcome was prevalence of fever burden over up to 14 days. The registry describes this as reduction in fever burden, in degrees C x hours, with intravenous ibuprofen compared with oral acetaminophen over the duration of treatment. Temperature readings were to come from bladder or esophageal probes. The record lists mean difference in inflammatory markers, difference in cost between ibuprofen and acetaminophen, and bleeding incidence as secondary outcomes.

The record states that data collection was incomplete because the principal investigator left before the data could be analyzed. It reports zero analyses. Thus, although the study design identifies an intended randomized comparison, the registry record does not provide an analyzed comparison of the groups. The planned sample-size illustration is not a report of observed power or evidence that the trial achieved a particular precision.

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

Analysis population for the primary outcome, as defined in the registry: PI left before data could be analyzed and data collection was incomplete.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Includes subjects from both arms as this information is only available for all subjects and not per arm.

6. Primary Endpoint

The registry lists the primary outcome as Prevalence of Fever Burden, measured over Up to14 days.

The primary endpoint is described as fever burden, expressed in degrees C x hours, over up to 14 days. The registry says that fever burden is calculated hourly by subtracting each patient's recorded temperature, measured with a bladder or esophageal probe, from 37 degrees C. It describes the primary comparison as reduction in fever burden with intravenous ibuprofen versus oral acetaminophen over the duration of treatment.

As a general statistical concept, an accumulated burden measure can represent both the level of a condition and how long it persists. Repeated temperature readings can therefore contribute to a summary across treatment, rather than reducing the comparison to a single temperature measurement. Such an endpoint may be useful when the study question concerns control over time.

The registry record does not report the observed endpoint values, a group difference, an uncertainty interval, or a test of the primary comparison. It also does not explain how missing temperature readings were handled, how the hourly measure was aggregated for participants, or how the stated calculation was translated into the reported “reduction” in fever burden. Because collection was incomplete and the record says the data could not be analyzed, the intended endpoint cannot be interpreted as a demonstrated difference between the treatment strategies.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, parallel-group, and unmasked. These design labels describe how the trial was intended to compare the assigned strategies; they do not by themselves establish that the resulting groups were comparable on every measured characteristic. The randomization procedure, allocation ratio, concealment method, and analysis population are not reported in the registry record.

What does randomization contribute?

General statistical explanation: random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. This supports interpretation of an outcome contrast as associated with assigned treatment, provided assignment and follow-up are implemented appropriately and the analysis respects the design. The record does not describe enough operational detail to evaluate those conditions, and it reports no outcome analysis.

How would the primary comparison be interpreted?

The primary outcome is fever burden in degrees C x hours. The registry describes hourly temperature readings and a comparison of reduction in burden between the treatment strategies. In general, an analysis would summarize the outcome for each assigned group and estimate a between-group contrast. An uncertainty interval would convey the range of effect sizes compatible with the observed data under the analysis assumptions; a narrow interval indicates more precision than a wide interval. Neither a contrast nor an interval is reported in the registry record.

General statistical explanation: an inferential test asks how compatible the observed data are with a specified null hypothesis, given the model and its assumptions. A p-value does not measure the probability that the null hypothesis is true, and it does not measure the clinical importance of a difference. The registry reports no primary-outcome test or p-value, so no such inference can be drawn for this trial.

What role do modeling assumptions play?

The sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not a report of the trial's own design justification. The sample-size justification for the trial is not reported in the registry record. The record does not provide a primary-outcome effect to interpret, and the illustration must not be treated as observed power.

General statistical explanation: a normal approximation can be useful when the modeled outcome and sample information make the approximation reasonable. If outcome values are highly variable or have a distribution poorly represented by the model, an approximation may be less reliable. The registry does not report the outcome distribution or a fitted model, so those properties cannot be assessed for this trial.

General statistical explanation: over-dispersion occurs when observed variability exceeds what a statistical model assumes. When present, it can make standard errors too small if not addressed, leading to intervals that are too narrow and tests that overstate precision. This is a general consideration, not a reported feature of this trial. No dispersion estimate or model diagnostics are reported in the registry record.

Can precision or power be assessed?

Precision is judged from an estimate and its uncertainty, not from enrollment alone. The registry records enrollment of 35, but it does not report how many participants contributed to the primary analysis, and it reports no analysis. Thus, no observed precision can be assessed from the primary outcome. Planning sample sizes, when available, describe hypothetical design performance under stated assumptions; they do not show the probability that this completed study detected an effect.

General statistical explanation: a confidence interval communicates uncertainty around an estimated effect, conditional on the data and methods used. It does not remove uncertainty due to missing data, bias, or model misspecification. Since no primary estimate or interval is reported, this usual tool for judging magnitude and precision is unavailable for the intended comparison.

How should the analysis record be read?

The registry lists four outcome measures and zero analyses. It gives the primary outcome description and names secondary outcomes, but does not report comparative estimates for them. The study's statistical analysis plan, including the model, covariate adjustment, handling of repeated readings, interim analyses, and multiplicity approach, is not reported in the registry record. These omissions prevent assessment of how the intended endpoint was to be reduced to a participant-level value and how comparisons were to be interpreted.

Overall, the methods information supports understanding of the intended randomized comparison and its endpoint, but not reproduction or evaluation of an outcome analysis. The main statistical conclusion is therefore about reporting availability: the record does not contain an analyzed treatment effect or its precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry names a primary outcome and lists secondary outcomes concerning inflammatory markers, cost, and bleeding incidence. It records four outcome measures and zero analyses. The registry record does not report a multiplicity procedure, a hierarchy for secondary outcomes, or a statistical analysis plan specifying which comparisons would be confirmatory. It is therefore not possible to determine how the risk of chance findings across multiple outcomes was to be addressed.

The record says data collection was incomplete because the principal investigator left before the data could be analyzed. It does not report the amount or pattern of missing primary-outcome data, the number of participants with usable measurements, or a method for handling missing observations. The missing-data assumptions and any sensitivity analyses are not reported in the registry record. Without those details, the impact of incomplete collection on a hypothetical treatment estimate cannot be quantified.

The analysis populations are also not reported in the registry record. For example, the record does not say whether an intended analysis would include all randomized participants according to their assigned groups or use another population. This matters because exclusions after randomization can affect how a group comparison is interpreted. No conclusion about the analysis population can be drawn from enrollment alone.

The registry's description of the outcome and its measurement does not specify how repeated readings, withdrawals, or partial treatment periods would contribute to an analysis. Interim analyses and stopping rules are not reported in the registry record. The study is marked terminated, but the reason for termination is not reported, and that status alone does not establish that a formal interim analysis occurred.

Consequently, both missing-data handling and multiplicity remain unresolved, while the primary and secondary outcome results are unavailable. These are limitations on interpretation, not evidence that a particular analytic choice was made.

11. 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 5% reporting threshold.

The registry's adverse-event record lists All Subjects, with 35 at risk for serious adverse events and 0 affected. It also lists 35 at risk for other adverse events and 0 affected, and deaths are recorded as 0. No serious adverse-event terms are listed.

These counts describe what is entered in the registry record. They do not show an arm-specific comparison: the safety entry is for All Subjects rather than separate ibuprofen and acetaminophen groups. The record does not report the length or completeness of safety follow-up, how adverse events were collected, or whether all participants completed the same observation period.

A count of zero recorded events should not be read as proof that no event could occur, or as a precise estimate that the strategies have identical safety. The study enrollment is 35, but the registry does not give group-specific safety counts or event-specific exposure information. The data collection note also says collection was incomplete. That does not establish that safety data were incomplete, but it is a reason to avoid extending the listed counts beyond what the record reports.

Accordingly, the safety entry supports only the narrow statement that the registry records zero serious events, zero other events, and zero deaths among the listed all-subject counts. It does not support a comparative safety conclusion.

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

The registry record establishes that a randomized, unmasked, parallel-group study was intended to compare intravenous ibuprofen with oral acetaminophen for fever control after non-traumatic brain hemorrhage. It records enrollment of 35 and describes fever burden as the primary outcome over up to 14 days. It also identifies secondary outcomes concerning inflammatory markers, cost, and bleeding incidence.

Those design details do not constitute a result. The record explicitly states that data collection was incomplete because the principal investigator left before data could be analyzed, and it lists zero analyses. No primary-outcome values, group contrast, confidence interval, or test result are reported. Therefore, the registry record cannot establish whether fever burden differed between the assigned strategies, the direction or size of any difference, or how precisely such a difference might have been estimated.

The same limitation applies to the secondary outcomes. Their names appear in the record, but comparative results are not reported. The listed safety counts are limited to the all-subject record and cannot establish a between-group safety difference.

The registry describes a rationale involving fever control and the potential drawbacks of shivering and sedating drugs used with body cooling. These statements provide context for the research question, not trial findings. The stated possibility of conducting a larger study of recovery is likewise not evidence about recovery in this study; recovery is not reported as the primary endpoint.

The most accurate conclusion is that the registry documents a planned randomized comparison but does not provide analyzed evidence answering its primary question. This absence of an analysis should not be mistaken for evidence of no difference, evidence of benefit, or evidence of equivalence. It also does not explain why the study was terminated; that reason is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a registered design and an interpretable result. Randomization and a clearly named primary endpoint describe how a comparison was intended to be made. They cannot substitute for outcome data, a treatment-effect estimate, and an account of uncertainty.

The endpoint focuses on fever burden accumulated over time, rather than a single temperature reading. As a general concept, this kind of measure can represent duration as well as intensity. It also requires clear rules for processing repeated measurements and incomplete observations. The registry gives a brief description of hourly temperature readings, but does not report the analysis details or an analyzed endpoint value. That gap makes the intended measure difficult to assess as an implemented analysis.

The record is also a reminder that enrollment and analysis are distinct. Enrollment of 35 is recorded, but the registry does not state how many participants contributed usable primary-outcome data or how observations were distributed between arms. With data collection incomplete and zero analyses listed, the registered sample cannot be translated into a reported estimate or precision assessment.

Finally, the record separates a research rationale from evidence. The background describes concerns related to fever, shivering, and sedating drugs, while the trial question concerns comparative fever burden. Neither rationale nor a proposed future study answers the present comparison. Reading the record carefully means retaining its design information while recognizing that the central statistical result is unavailable.

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 most consequential limitation is the absence of an analyzed primary outcome. The registry says collection was incomplete because the principal investigator left before data could be analyzed, and lists zero analyses. It does not report the amount, timing, or distribution of missing data, so the effect of incompleteness on the intended comparison cannot be assessed.

Several design and analysis details are not reported in the registry record: the randomization method, allocation ratio, concealment, analysis population, outcome aggregation rules, handling of missing readings, statistical model, and multiplicity approach. These details would be needed to assess whether the analysis followed the design and how robust any comparison might be.

The primary endpoint description identifies temperature probes and an hourly calculation, but does not report observed values or explain fully how the calculation produced a participant-level outcome. No group-specific results are reported for the secondary outcomes. The reason for termination is not reported in the registry record, and the status alone does not identify the cause.

The adverse-event entry is presented for All Subjects, not by randomized group. It records zero serious events, zero other events, and zero deaths, but follow-up duration and safety data completeness are not described. These counts therefore cannot support an arm-to-arm safety comparison.

Finally, enrollment of 35 does not establish the precision of an outcome estimate when no analysis is reported and the number with usable measurements is unknown. The record's planning assumptions do not resolve that limitation: they are not the trial's own documented sample-size justification and are not observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage — NCT01530880.
• Registry record last updated 2017-08-28; status last verified 2017-08.
• Results first posted 2017-08-28.
• 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

NCT01530880 is a phase 4 randomized, parallel-group study with no masking, sponsored by Columbia University. The registry records enrollment of 35, a start date of 2012-10, primary completion on 2016-03-17, and status of terminated. The reason for termination is not reported in the registry record.

The study intended to compare intravenous ibuprofen with oral acetaminophen for fever control after non-traumatic brain hemorrhage. Its primary outcome was fever burden in degrees C x hours over up to 14 days. Listed secondary outcomes concern inflammatory markers, cost, and bleeding incidence.

The registry states that data collection was incomplete because the principal investigator left before data could be analyzed. It reports zero analyses and no comparative primary-outcome results. The all-subject safety entry lists 35 at risk and 0 affected for serious and other adverse events, with 0 deaths. These record entries do not provide treatment-arm comparisons.