Immunomodulatory Properties of Ketamine in Sepsis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunomodulatory Properties of Ketamine in Sepsis (NCT01089361), a randomized phase 1, phase 2 study. The primary outcome is Serum Levels of IL-6, IL-10 and TNFα.

2. Clinical Question

The study also listed morbidity, mortality and adverse effects among its aims or secondary outcomes. Those outcomes are distinct from the primary immune-marker question: a finding about a cytokine measurement would not by itself establish a difference in organ failure, ICU stay, mortality or safety. The posted information should therefore be read as describing the trial question and its recorded outcomes, rather than as a complete answer about the effects of ketamine.

3. Trial Design

The registry identifies this as a phase 1 and phase 2, randomized, quadruple-masked, parallel-group trial. Enrollment was 19, and the status is completed. The record names Beth Israel Deaconess Medical Center as sponsor. The start is listed as 2009-12 and primary completion as 2010-06. These are registry dates and do not, by themselves, describe how long each participant was followed.

The two groups were ketamine and normal saline placebo. Their administration schedules were described in parallel: an initial infusion over one hour followed by continuous infusion for a further 23 hours. The registry calls the ketamine regimen an analgesic dosage, but does not report additional details about dose selection or protocol rationale.

Random allocation is intended, in general, to make treatment groups comparable on average with respect to measured and unmeasured characteristics. Masking is intended to reduce the influence of knowledge about assigned treatment on care, outcome assessment, or reporting. The registry term “quadruple” identifies the stated masking category, but the specific people masked and the procedures used to maintain masking are not reported in the registry record. The parallel model means the record describes separate treatment groups rather than a within-participant crossover.

The small enrollment is important context for reading any group comparisons. With few participants, estimates can be imprecise, and the distribution of characteristics may differ between groups by chance despite randomization. The registry record does not report a sample-size justification, recruitment flow, baseline characteristics, adherence, or details of exclusions from analyses. It also does not report the statistical plan or interim analyses. Those omissions limit assessment of how the recorded design was implemented and how planned analyses relate to any results.

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: All patients who consented were randomized to treatment or placebo.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Serum Levels of IL-6, IL-10 and TNFα, measured over first 7 days of admission, Baseline and Day 7 reported.

The primary outcome is serum levels of IL-6, IL-10 and TNFα, expressed in pg/mL. These are cytokines, signaling molecules involved in immune responses. In general, measuring such markers can help characterize biological responses associated with an illness or a treatment. The trial description frames the measurement as a way to assess whether ketamine modulates the cytokine response to sepsis.

The registry specifies median and inter-quartile range as the summary format. A median describes the center of an ordered set of measurements; the inter-quartile range describes the spread of the central portion of those measurements. These summaries are often useful when data are skewed or contain values that make a mean and standard deviation less representative, though the registry does not state why this format was selected.

The outcome timeframe is described as the first 7 days of admission, with Baseline and Day 7 reported. These are repeated measurement occasions for the listed markers, not a single endpoint value. The registry record does not report actual marker values, a treatment-group contrast, or a defined method for combining the cytokines or time points into one comparison. The primary outcome therefore cannot be reduced to a single estimate of difference from the posted information. The record also does not explain whether the analysis focused on change from baseline, Day 7 values, or another comparison across time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General: Randomization assigns participants to treatment groups by chance. Its statistical purpose is to reduce systematic differences between groups at the start of a trial, including differences that investigators may not have measured. It does not guarantee that groups will be identical, especially in a small study. The registry describes this trial as randomized, but the sequence-generation method, allocation concealment procedures and group-specific baseline characteristics are not reported in the registry record. The label alone therefore does not permit an assessment of those implementation details.

What does masking mean for interpretation?

General: Masking can limit bias when expectations might influence clinical care, outcome assessment or participant reporting. The registry calls the trial quadruple-masked. That label should be reported as recorded, without assuming which roles were masked or how masking was maintained; those details are not reported in the registry record. Masking also does not resolve other sources of uncertainty, such as incomplete outcome measurement or choices among multiple outcomes.

Why summarize the primary outcome with medians and inter-quartile ranges?

The primary outcome lists serum IL-6, IL-10 and TNFα levels in pg/mL, with median and inter-quartile range summaries. General: A median is the midpoint of ordered observations. The inter-quartile range describes the spread of the middle half of the observations. These summaries can be informative when measurements are asymmetric or include extreme values, because they are less influenced by extremes than a mean. The registry does not report whether the distributions were assessed or why these summaries were selected, so the choice should not be taken as evidence about the actual data distribution.

A median and inter-quartile range describe each set of measurements; they do not, alone, quantify a treatment contrast or its uncertainty. A comparison might be framed using a difference between group summaries, a model-based estimate, or another method. The registry record does not report which comparison method was used. Nor does it report the numerical medians or inter-quartile ranges for the treatment groups.

How should multiple markers and measurement occasions be understood?

The primary outcome includes three cytokines and identifies Baseline and Day 7 within the first 7 days of admission. General: Repeated measurements can be analyzed by comparing groups at a specified time, comparing change from baseline, or modeling measurements over time. These approaches answer related but different questions. A time-course model can also account for the fact that measurements from the same participant are related, rather than treating them as unrelated observations. The registry record does not identify which approach, if any, was used.

Multiple markers and time points also create multiple potential comparisons. General: When many hypotheses are tested, the chance of at least one apparently unusual result can increase. Statistical approaches to multiplicity may adjust significance thresholds, define a hierarchy of outcomes, or distinguish confirmatory from exploratory analyses. The registry does not report a multiplicity strategy, and no single primary comparison is identified in the registry entries. Thus, a reader cannot determine how any potential findings across markers and occasions would have been interpreted together.

What do p-values and confidence intervals ordinarily add?

General: A p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the test. It does not measure the probability that a treatment works, and it does not describe the magnitude or clinical importance of an effect. A confidence interval gives a range of estimates compatible with the data and method at the stated confidence level. The registry record does not report a primary-outcome p-value, confidence interval or effect estimate, so neither statistical evidence nor precision can be assessed for the cytokine comparison.

General: When counts are sparse, standard approximations may be unreliable, and exact or other methods may be considered. When continuous measurements are skewed, distributional assumptions and the choice of summary or model can matter. No analysis method is reported for the primary outcome or safety counts, so no particular method should be attributed to this trial.

What can be inferred from the planning information?

The general planning assumptions listed for illustrative calculations are a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry record does not report the trial's own sample-size justification or the effect size used in its original design. The primary comparison is not reduced to one estimate in the record, so the planning assumptions do not resolve what effect was actually observed or how precisely it was estimated.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome encompasses three serum cytokines and more than one measurement occasion: Baseline and Day 7 within the first 7 days of admission. This creates several possible ways to define a treatment comparison. The registry record says the outcome has several categories or time points and was not reduced to one comparison. It does not identify a preferred marker, time point, change score or combined endpoint, and it does not report a multiplicity strategy.

General: Multiplicity matters because examining many outcomes or contrasts can increase the chance of finding an apparently notable result by chance. Prespecified outcome hierarchies, adjusted testing procedures or explicit exploratory labeling can help readers understand how a set of comparisons was interpreted. The registry record does not report whether any such approach was used. No p-values or test results are reported for the primary outcome, so there is no basis to assess how multiplicity affected statistical conclusions.

Missing-data handling is also not reported in the registry record. The posted information does not specify whether all randomized participants contributed measurements at each occasion, how unavailable measurements were treated, or whether any imputation or sensitivity analysis was conducted. This matters because analyses based only on participants with recorded measurements may be affected if missingness is related to participant condition or treatment. No analysis population is described, including whether the primary analysis followed randomized assignment or used another population definition.

The record lists enrollment of 19 and zero analyses, but these registry entries do not reveal the number contributing to each outcome analysis. A completed status likewise does not establish how missing outcome data or exclusions were handled. Without analysis-population definitions, participant flow and missing-data methods, the comparability and completeness of the primary outcome data cannot be assessed.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (44.4%), pericardial effusion (10.0%), ventricular tachycardia (10.0%).

The safety record reports serious adverse events for Normal Saline and Ketamine separately. For Normal Saline, 9 participants were at risk and 4 were affected; for Ketamine, 10 were at risk and 4 were affected. These are recorded group counts. They do not, by themselves, describe the type, timing, severity distribution or causal relationship of each event, and the registry record does not report an analysis comparing the groups.

The registry also lists other adverse events: 0 of 9 at risk in the Normal Saline group and 5 of 10 at risk in the Ketamine group were affected. These “other” event counts should not be merged with the serious-event counts. The record does not provide further detail about how the categories were defined or whether participants could contribute more than one event.

The listed top serious terms are Death at 44.4%, Pericardial effusion at 10.0% and Ventricular tachycardia at 10.0%. The registry record does not specify the denominator or arm attribution for these percentages in the registry record, so they should not be interpreted as treatment-specific risks. The deaths field for each group is null; this is not a numerical count and does not establish that there were no deaths. The event-term listing and group-level affected counts therefore do not support a causal conclusion about ketamine. They are descriptive registry information, with important details of denominator, event counting and attribution not reported in the registry record.

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

The record establishes that a randomized, quadruple-masked, parallel-group study of ketamine and normal saline placebo was completed, with enrollment of 19 participants. It identifies serum IL-6, IL-10 and TNFα levels as the primary outcome and describes the measurement summaries and occasions. It also lists secondary outcomes addressing adverse effects, organ failures, APACHE scores, ICU stay and 28 Day Mortality. These details clarify the research question and the types of outcomes the investigators intended to examine.

They do not establish that ketamine did or did not change cytokine levels. The registry record does not report the primary marker results or a single treatment contrast. It therefore gives no estimate of the direction, size or precision of a primary-outcome effect. Lack of a reported result should not be treated as evidence of no difference. It is also not possible to infer a result from the study's completed status or from the stated hypothesis.

The recorded safety counts are descriptive and do not demonstrate that events were caused by treatment or that the groups differed reliably. The serious-event term percentages lack reported denominator and arm attribution in the registry record, while group-specific deaths are not numerically reported. The secondary outcome list similarly does not provide outcome findings.

General: A clinical trial's interpretation depends on more than its design label. Readers need outcome estimates, uncertainty measures, analysis methods, and information about missing observations and the populations analyzed. Those elements help distinguish a potentially meaningful difference from random variation or limitations in measurement. The registry record does not report these details for the primary comparison.

Accordingly, the defensible interpretation is limited to the trial's recorded design, outcome definitions and available adverse-event counts. No conclusion about clinical benefit, harm or comparative effectiveness follows from the information. Further results and methods would be needed to assess the trial's findings and their precision.

13. Why This Trial Matters Statistically

This trial is statistically notable as a small randomized study with a biological primary outcome and multiple measurement dimensions. The registry reports enrollment of 19 and identifies three cytokines, each measured at Baseline and Day 7. That structure illustrates why a primary outcome needs a clearly defined comparison: several markers and occasions can generate several distinct estimates, each answering a different question.

The registry does not reduce the primary outcome to one comparison. This is important for interpretation, not merely presentation. A single prespecified contrast can clarify which estimate is central and how secondary or exploratory findings relate to it. When a record lists several outcome components without an analysis summary, readers cannot determine which contrast was intended to carry the main evidential weight or how multiplicity was addressed.

The record also illustrates the distinction between trial completion and result reporting. The study is marked completed, yet the registry entries available do not include numerical primary-outcome results, analysis methods, or missing-data handling. A design description can explain how a trial was organized, but it cannot replace results and uncertainty estimates. Similarly, counts of participants affected by adverse events do not provide a complete comparative safety analysis without definitions, timing, attribution and analysis details.

General: Small studies can be valuable for assessing feasibility, describing biological measurements and generating questions for further research. Their estimates may be imprecise, and chance imbalances can occur even with random allocation. The size of this trial makes careful attention to uncertainty especially relevant, but no particular uncertainty interval is reported in the registry record.

The statistical lesson is that outcome definition, transparent analysis and reporting are essential to make a trial interpretable. The registry captures a research question and design, but the registry entries do not permit evaluation of the primary effect. This distinction helps prevent the design and hypothesis from being mistaken for evidence of a 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 primary limitation for interpretation is the absence of numerical results for the primary outcome. The registry identifies IL-6, IL-10 and TNFα, their units and summary format, but does not report their group values or a treatment contrast. It also does not reduce the multiple markers and time points to one comparison. As a result, the direction, magnitude and precision of the primary finding cannot be assessed.

The record does not report the statistical analysis plan, analysis populations, missing-data methods or the methods used to handle repeated measurements. It also does not report multiplicity procedures, interim analyses or a sample-size justification. These omissions prevent evaluation of whether analyses followed a prespecified plan, how incomplete measurements were treated, or how results across outcomes would be interpreted.

Enrollment was 19, but the registry entries do not describe participant flow or the number contributing to each outcome. The record does not report eligibility criteria beyond the condition and study aim, group baseline characteristics, adherence or treatment discontinuations. The randomized and quadruple-masked labels are recorded, but implementation details are not reported in the registry record.

Safety interpretation is limited by incomplete context for the serious-event terms. Denominators and arm attribution for the listed percentages are not reported in the registry record, and the deaths entries are null rather than numerical. The registry also does not provide event timing, definitions or a comparative safety analysis. These limitations mean that the available counts should be read descriptively and not as causal evidence.

Finally, the listed secondary outcomes are not accompanied by numerical results in the registry record. The completed status and stated study hypothesis do not fill these gaps. These limitations are specific to the recorded information and do not establish what may or may not have been assessed outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunomodulatory Properties of Ketamine in Sepsis — NCT01089361.
• Registry record last updated 2017-08-21; status last verified 2017-07.
• Results first posted 2017-08-21.
• 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

NCT01089361, “Immunomodulatory Properties of Ketamine in Sepsis,” is recorded as a completed phase 1 and phase 2 randomized, quadruple-masked, parallel-group trial sponsored by Beth Israel Deaconess Medical Center. Enrollment was 19. The record lists a start of 2009-12 and primary completion of 2010-06.

The intervention was ketamine and the comparator was normal saline placebo. The primary outcome was serum IL-6, IL-10 and TNFα in pg/mL, summarized as median and inter-quartile range, with Baseline and Day 7 identified during the first 7 days of admission. Secondary outcomes include adverse effects attributable to ketamine, organ failures, APACHE scores, ICU stay and 28 Day Mortality.

The record does not report a single primary-outcome comparison or numerical cytokine results. It lists group-level adverse-event counts, but key context for interpreting the serious-event terms is not reported in the registry record. The posted information therefore describes the design and recorded outcomes without establishing treatment effects.