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 Pharmacokinetic Alterations During ECMO (NCT01938079), a randomized na study. The primary outcome is Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01938079 |
| Phase | NA |
| Condition | Acute Respiratory Failure |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Columbia University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with acute respiratory failure receiving extracorporeal membrane oxygenation (ECMO) support and a sedative drug regimen. The registry description explains that ECMO can assist patients with severe lung failure while they recover. Further eligibility details, including age limits and other clinical characteristics, are not reported in the registry record.
Intervention
A sedative drug regimen with ketamine. The trial description identifies continuous intravenous ketamine as the intervention of interest, while the arm description states that participants received the sedative regimen with ketamine. Dose, treatment duration, and rules for adjusting ketamine are not reported in the registry record.
Comparator
A sedative drug regimen without ketamine. This is the randomized comparison arm. The record does not specify the particular sedative drugs, whether background regimens were standardized, or how clinicians adjusted those regimens.
Primary question
Does adding ketamine to the sedative regimen change the cumulative fentanyl-equivalent amount recorded from ECMO initiation to the decision to achieve wakefulness? The endpoint is reported in mg, with results summarized by medians and interquartile ranges. The registry's endpoint description also refers to a combination of sedative drug regimen, so the precise operational definition is not fully clear from the record.
3. Trial Design
This was a randomized, parallel-group trial with no masking, listed as phase NA. The registry record describes two regimens: a sedative drug regimen without ketamine and the same broad regimen category with ketamine. Enrollment was 20, with 10 participants in each arm. The study status is completed. Its listed start was 2013-09 and its primary completion was 2015-02.
The study focused on patients with acute respiratory failure receiving ECMO. Its rationale describes the possibility that drugs may bind to internal machine surfaces and thereby have lower concentrations, and notes that patients on ECMO may receive pain medicines and sedatives. The stated hypothesis was that continuous intravenous ketamine could reduce requirements for other pain medicines while the desired level of sedation was achieved. The posted primary outcome, however, is a cumulative fentanyl-equivalent measure, rather than a direct measure of sedation level or pain relief.
Randomization can help balance prognostic factors between comparison groups on average, but the record does not report how the sequence was generated, how allocation was concealed, or whether any stratification was used. Masking is listed as none. The specific clinical procedures, co-interventions, and criteria for deciding when to pursue wakefulness are not reported in the registry record. Nor does the record describe a formal sample-size justification or give a protocol-level statistical analysis plan.
The arm-level results are descriptive: each group has a reported median and interquartile range. No inferential analyses are posted. The enrolled number is modest, and the spread of the outcome values is broad in both arms. Those features matter when interpreting how much confidence can be placed in an apparent difference between medians. The observed arm summaries alone do not establish whether an underlying difference is compatible with chance variation or whether it is clinically meaningful.
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 | Sedative Without Ketamine | Sedative With Ketamine |
|---|---|---|
| STARTED | 10 | 10 |
| COMPLETED | 10 | 10 |
| 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 | Sedative Without Ketamine | Sedative With Ketamine | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Continuous | years | 44 (25 to 58) | 43 (36 to 52) | 44 (29 to 57) |
| Sex: Female, Male: Female | Participants | 5 | 6 | 11 |
| Sex: Female, Male: Male | Participants | 5 | 4 | 9 |
| Region of Enrollment: United States | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness, measured over Up to 14 days.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness.” It is measured in mg and summarizes the accumulated amount over the stated period, up to 14 days. A cumulative medication measure can capture overall exposure across a treatment interval rather than describing a single dose or a single time point. In this study, it was selected to address the hypothesis about requirements for other pain medicines during ECMO support.
The endpoint is summarized as a median with an interquartile range. The median describes the middle of the ordered observations, while the interquartile range describes the central half of the observed values. These summaries are useful when values are unevenly distributed or when some observations are much larger than others, because they do not depend on the arithmetic mean in the same way.
The registry description has an important wording ambiguity: although the endpoint title specifies cumulative fentanyl equivalents, its description calls the measure a combination of the sedative drug regimen. The exact conversion method, included medicines, data-collection procedures, and handling of treatment changes are not reported in the registry record. The results should therefore be interpreted as the registry's reported cumulative fentanyl-equivalent endpoint, without assuming additional details about its construction.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The median cumulative fentanyl-equivalent result was 330.0 mg in the sedative-without-ketamine arm, with an interquartile range from 101.0 to 1971.0 mg. In the sedative-with-ketamine arm, the median was 834.0 mg, with an interquartile range from 379.0 to 2329.0 mg. Each arm included 10 participants. These are descriptive summaries of the observed groups, not estimates accompanied by a reported inferential comparison.
The medians are different, and the reported interquartile ranges are broad. The ranges overlap. Such overlap is not itself a formal test of a difference, and it cannot establish whether the observed median contrast is statistically distinguishable from random variation. Conversely, overlap does not prove that the groups are equivalent. No confidence interval for a between-arm contrast, p-value, or other inferential result is reported in the registry record.
The trial's stated hypothesis concerned lower requirements for other pain medicines with ketamine while achieving the desired sedation level. The posted endpoint is cumulative fentanyl equivalents, and the observed median is higher in the ketamine arm than in the arm without ketamine. This descriptive direction is not a causal conclusion. The study is randomized, but the record provides no inferential analysis to quantify uncertainty around the contrast, and the endpoint description does not fully specify the medication calculation. It also does not report a separate result for sedation achievement or a direct measure of pain relief.
The interquartile ranges indicate substantial variation in recorded values within each group. A median alone would not convey that spread; the ranges help show that participant outcomes were not concentrated near a single value. With 10 participants per arm, the group summaries may be sensitive to the particular observations included. The registry does not report individual-level values, a confidence interval for either median, or an analysis adjusted for baseline characteristics.
Accordingly, the posted results describe the distributions' central values and spread in this small randomized comparison. They do not establish the size or precision of a treatment effect, nor do they support a conclusion about equivalence or a definitive effect on medication requirements. The data also cannot, by themselves, resolve whether ketamine changed the level of sedation achieved or the timing of the decision to pursue wakefulness. Those interpretations would require further outcome definitions and analyses, which are not reported in the registry record.
9. Statistical Methods Explained
The main posted summaries are medians and interquartile ranges. A median is the central value after observations are ordered from smallest to largest. It is often useful for outcomes with skewed distributions, where a small number of large observations can pull the arithmetic mean away from the typical observation. The median does not describe every participant, so it is best read alongside a measure of spread.
An interquartile range gives the lower and upper boundaries of the central half of the observations. It indicates how dispersed the middle portion of the results is, but it does not show the full range or reveal the exact pattern of individual values. In this trial, both arms have broad reported interquartile ranges. The registry does not provide a separate standard deviation, full range, or participant-level outcome data.
What does randomization contribute?
Random allocation is intended to make comparison groups similar with respect to factors that may affect outcomes, on average. It does not guarantee that small groups will have identical characteristics, and it does not remove uncertainty due to the number of participants. The registry labels the study randomized but does not report the sequence-generation method, allocation concealment, stratification, or baseline comparability. The absence of those details in the record should not be filled in by assumption.
What does the arm-level contrast establish?
A difference between observed medians describes the enrolled participants. An inferential analysis would quantify how uncertain a comparison is under a specified statistical model or test. Common ways to report that uncertainty include a confidence interval for the contrast and a p-value. Neither is reported for this endpoint. A confidence interval, in general, is a range of values produced by a method designed to reflect uncertainty in an estimate. It would not guarantee that the true effect lies within any particular interval, and its interpretation depends on the method and assumptions used.
No between-arm effect estimate or confidence interval is posted, so the precision of the contrast cannot be assessed from an inferential result. The broad within-arm ranges give useful context about variability, but they are not a substitute for a confidence interval around the difference between groups. Likewise, the presence or absence of overlap between group ranges is not a formal test of the treatment contrast.
Why might a mean-based model need care?
Medication totals can vary markedly between participants. In general, when outcome variability is much greater than a statistical model expects, standard errors and tests based on that model may not be reliable unless the model accounts for the extra variability. This is often described as over-dispersion in settings where a model assumes a particular variance structure. The registry does not report a fitted model, an over-dispersion assessment, or a rationale for selecting the median-based summary. The posted summaries therefore should not be represented as evidence that any particular model was used.
What analyses are posted?
The registry reports one primary outcome measure and no analyses. It gives arm-level medians and interquartile ranges but no adjusted or unadjusted inferential comparison. There is no reported hypothesis test, model specification, covariate set, missing-data method, or analysis population definition. Details such as whether the primary comparison was intended to use a rank-based test, a transformation, or a regression model are not reported in the registry record.
These distinctions matter because different methods answer somewhat different questions. A comparison of medians, a comparison of means, and a model-based estimate need not produce identical results, especially for skewed data. Without a stated analysis plan and an inferential result, the posted descriptive summaries should be read on their own terms rather than treated as a completed statistical test.
How should planning calculations be understood?
Planning calculations use assumptions about the effect to detect, variability, significance threshold, and allocation to estimate the number of participants that a design might require. They are not results observed in the trial and do not show the probability that a completed trial has found a true effect. The stated planning framework describes a two-sided significance level of 0.05, equal allocation, and a normal approximation, with planning effects expressed as fractions of an observed effect. Any such calculations are illustrative rather than the trial's own design justification. A formal sample-size rationale is not reported in the registry record. No numeric planning estimates are reported in the registry record.
In general, calculations that use an observed effect as their starting point are especially sensitive to uncertainty in that observed effect. Small trials can produce unstable effect estimates, so a planning illustration based on those estimates should not be interpreted as observed power or as proof that the study was adequately sized. The registry does not report a protocol-based target sample size or a rationale for the enrollment of 20.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and no secondary outcomes. No analyses are posted. A multiplicity strategy—such as whether any adjustment was planned for multiple outcomes, comparisons, or interim looks—is not reported in the registry record. Since no inferential analyses are reported, there is no posted family of p-values from which to assess how multiplicity was handled.
Missing-data details are also not reported. The record does not state whether all randomized participants contributed endpoint data, whether any observations were unavailable, or how incomplete medication records or early discontinuation were handled. It does not describe imputation, exclusion rules, or sensitivity analyses. The reported enrollment and arm sizes do not, by themselves, establish that every participant had a complete endpoint observation.
The analysis population is not defined in the registry record. It is therefore unclear whether results were intended to include all randomized participants according to assigned arm, only participants who received the assigned regimen, or another population. The record also does not specify how deviations from assigned treatment or changes in sedative regimens were handled analytically.
There is no reported interim-analysis plan, stopping rule, or monitoring procedure. These absences do not show that such procedures were or were not used; they mean that they cannot be assessed from the registry record. Likewise, no protocol-level statistical analysis plan is reported. These reporting gaps limit the ability to determine whether the posted descriptive summaries correspond to a prespecified analysis and how missing observations or deviations could have influenced them.
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 |
|---|---|---|---|
| Sedative Without Ketamine | 0 | 10 | 0.0% |
| Sedative With Ketamine | 0 | 10 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sedative Without Ketamine | 0 of 10 |
| Sedative With Ketamine | 0 of 10 |
The registry reports 0 serious adverse events among 10 participants in the sedative-without-ketamine arm and 0 among 10 participants in the sedative-with-ketamine arm. It also reports 0 other adverse events among 10 participants in each arm. These are event counts as posted for the two groups.
The death values are not reported in the registry record. The reported zero counts for serious and other adverse events should not be interpreted as proof that no adverse experiences occurred beyond the categories or reporting period captured by the record. The registry does not provide event descriptions, severity criteria, attribution, follow-up completeness, or the method used to collect adverse events. It also does not provide a detailed safety analysis or an uncertainty estimate for the event counts.
With 10 participants per arm, the adverse-event summaries are limited descriptions of the enrolled groups. They cannot establish that risks are the same between regimens or rule out uncommon events. The figures should be read as registry-reported counts, not as a comprehensive assessment of safety or as medical advice.
12. What the Result Does, and Does Not, Mean
The results describe a small randomized comparison of sedative regimens during ECMO, with and without ketamine. The primary endpoint records cumulative fentanyl equivalents from ECMO initiation to the decision to achieve wakefulness, over a timeframe of up to 14 days. The registry reports a median of 330.0 mg in the arm without ketamine and 834.0 mg in the arm with ketamine. The interquartile ranges are wide, and no inferential comparison is posted.
These data do not establish that either regimen caused a particular amount of medication use. Randomization supports a comparative design, but the registry's descriptive results do not quantify uncertainty around the contrast. Without a confidence interval, p-value, or other reported analysis, the apparent difference between medians cannot be classified as statistically significant, statistically non-significant, or evidence of equivalence.
The stated hypothesis also concerned achieving a desired level of sedation while reducing requirements for other pain medicines. The registry does not report a separate sedation outcome, a pain-relief outcome, or detailed medication-level results. The endpoint's description is not fully consistent with its title, and its precise construction is not reported. Thus, the posted outcome cannot answer every element of the broader hypothesis.
The absence of reported serious or other adverse events in the listed groups is a limited event-count summary, not proof of safety. Death counts are not reported in the registry record, and adverse-event collection details are absent.
In general, a registry result is most informative when the outcome definition, analysis population, statistical method, and uncertainty estimates are available alongside group summaries. Those details are not reported for this comparison. The results are best understood as descriptive observations from the enrolled participants, with substantial within-arm variation and important uncertainty about the precision and meaning of the between-arm contrast.
13. Why This Trial Matters Statistically
This trial raises a statistical problem common in clinical research: a plausible biological or pharmacological question must be translated into a measurable endpoint. The study rationale concerns whether ketamine changes requirements for other pain medicines during ECMO while sedation is maintained. The registry's primary outcome is a cumulative fentanyl-equivalent measure. Such an endpoint can summarize medication exposure over time, but its interpretation depends on which medicines are included, how equivalence is calculated, and how treatment changes are recorded. Those operational details are not reported in the registry record.
The study also illustrates why center-of-distribution summaries and uncertainty measures answer different questions. Medians and interquartile ranges describe the observed arms, and the reported ranges are broad. Without an inferential contrast, the precision of the between-arm result is not established. This matters especially in a small randomized trial, where chance imbalance and variation across participants can have a substantial influence on group summaries.
Another statistical lesson is that a randomized design does not make every reporting gap disappear. Randomization is valuable, but interpretation still depends on knowing how allocation was implemented, how the endpoint was defined, which participants were analyzed, and how missing data were treated. Those details are not reported in the registry record.
Finally, this example separates a clinical hypothesis from what the posted outcome directly measures. A cumulative medication endpoint may inform the medication-use question, but it does not on its own establish the achieved level of sedation, patient comfort, or other clinical outcomes. Clear endpoint definitions and appropriately reported uncertainty are essential for connecting a statistical result to the question researchers intended to answer.
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 main limitation specific to interpretation is the endpoint wording. The title identifies cumulative fentanyl equivalents, while the description characterizes the measure as a combination of the sedative drug regimen. The registry does not explain the conversion formula, which drugs contributed, or how cumulative amounts were assembled. Readers cannot independently determine the exact clinical quantity represented by the reported mg values.
The record gives medians and interquartile ranges for 10 participants in each arm, but no inferential analyses. There is no reported estimate of the between-arm contrast with a confidence interval, nor a p-value. The broad within-arm ranges also indicate considerable dispersion in the posted summaries. The available results therefore provide limited information about the precision of a comparative effect.
Several design and analysis details are absent. The allocation sequence and concealment methods are not reported; masking is listed as none. The record does not describe specific sedative regimens, dose-adjustment practices, adherence, baseline characteristics, or the decision criteria for achieving wakefulness. It does not define an analysis population or explain missing data and protocol deviations.
The adverse-event record contains zero reported serious and other adverse events in each group, but event definitions and collection methods are not reported; death counts are also not reported in the registry record. Finally, no protocol-based sample-size rationale or statistical analysis plan is reported. These limitations constrain what can be inferred from the posted results and should not be filled with assumptions about the trial's conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetic Alterations During ECMO — NCT01938079.
- Registry record last updated 2016-09-29; status last verified 2016-08.
- Results first posted 2016-09-29.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
Pharmacokinetic Alterations During ECMO (Ketamine and Extracorporeal Membrane Oxygenation), NCT01938079, is listed as a completed randomized, parallel-group study with no masking and phase NA. Columbia University is the listed sponsor. The registry record lists a start of 2013-09, primary completion of 2015-02, and enrollment of 20.
The trial compared a sedative drug regimen without ketamine with a regimen with ketamine among patients with acute respiratory failure receiving ECMO. Its single reported primary outcome was cumulative fentanyl equivalents from ECMO initiation to the decision to achieve wakefulness, measured in mg over up to 14 days. Results are presented as arm-level medians and interquartile ranges, with 10 participants in each arm. No inferential analyses or secondary outcomes are posted. The record reports zero serious and other adverse events in each group; death counts are not reported in the registry record.