Ketamine to Improve Recovery After Cesarean Delivery - Part 1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine to Improve Recovery After Cesarean Delivery - Part 1 (NCT04037085), a na phase 2 study. The primary outcome is Ketamine (AUC).

2. Clinical Question

The broader study objective includes evaluating ketamine pharmacokinetics and pharmacodynamics, transfer into breastmilk, and effectiveness after cesarean delivery. Part 1 focuses on physiochemical assessment of ketamine and its metabolites, breastmilk transfer, and calculated estimates of neonatal and infant exposure. The primary endpoint listed for this part is ketamine AUC, rather than a comparison of pain or opioid-use outcomes.

The study description distinguishes Part 1 from a planned Part 2. Part 2 is described as a larger randomized controlled trial continuing PK/PD assessments and including postpartum pain, depression scores, central sensitization measures, patient-reported recovery, breastfeeding, and parent-infant bonding. Those planned Part 2 assessments do not turn Part 1 into a randomized comparison, and their results are not reported in the registry record for this Part 1 analysis.

3. Trial Design

This is a completed Phase 2 study with a single-group model. The registry lists allocation as not applicable and masking as none. Eight participants were enrolled. With no control group and no random allocation, the design describes observations following ketamine administration rather than a randomized estimate of the difference between ketamine and another treatment or usual care.

The intervention is listed as ketamine, given intravenously after cord clamping, with an infusion for 12 hours. The arm description also specifies an intravenous ketamine infusion for 12 hours in the weaning population at the Montefiore CTRC. The registry does not report the numbers of participants in each described setting separately.

The recorded study start was 2019-10-09, primary completion was 2021-08-01, and status is completed. The study title identifies this as Part 1, while its official title emphasizes pharmacokinetics/pharmacodynamics, breastmilk transfer, and effectiveness after cesarean delivery. The description says Part 1 assesses drug and metabolite measurements and calculated neonatal and infant exposure estimates. It describes Part 2 separately as a larger randomized controlled trial with broader clinical and recovery outcomes.

The primary outcome is ketamine AUC over the 12 hour infusion, expressed in mcg*min/mL. Although the outcome definition specifies a mean and standard deviation, numerical results for this endpoint are not reported in the registry record. The record lists nine outcome measures and zero analyses. A sample-size justification, detailed statistical plan, interim analyses, and specific analysis populations are not reported in the registry record.

The single-group structure is important when interpreting the study. It can describe measurements in participants who received the intervention, but by itself it cannot provide a randomized between-group treatment contrast. The registry record does not describe a comparator for Part 1, and no comparative effect should be inferred from its design.

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

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 Ketamine (AUC), measured over 12 hour ketamine infusion.

The primary endpoint is ketamine area under the plasma concentration-time curve, or AUC, during the 12 hour ketamine infusion. Plasma is used to calculate AUC 0-∞. Its stated unit is mcg*min/mL, and the planned summary is a mean with standard deviation.

AUC represents exposure over time: it combines drug concentration measurements across the concentration-time profile rather than describing concentration at just one moment. In general, this type of pharmacokinetic measure is used to characterize the amount of drug exposure after administration. The registry’s description says the AUC reflects actual body exposure after a dose.

For this study, AUC is a pharmacokinetic endpoint. It does not, on its own, measure pain relief, opioid use, depression, breastfeeding success, or infant outcomes. Those topics appear in the broader study description, particularly for Part 2, but the primary endpoint specified for Part 1 is ketamine exposure.

The record does not report the observed mean or standard deviation for the primary endpoint, nor does it provide a numerical estimate of AUC. It therefore does not support a quantitative description of the observed exposure or its variability. The stated endpoint definition explains what investigators intended to measure, but is not itself a result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous pharmacokinetic measure: ketamine AUC during the 12 hour infusion, with units of mcg*min/mL. The record specifies a mean and standard deviation as the summary. A mean describes the central value of a set of measurements, while a standard deviation describes how spread out individual measurements are around that mean. These are descriptive statistics; without their numerical values, readers cannot tell the observed average exposure or the variability in this cohort.

What does AUC represent?

In general, area under a concentration-time curve combines drug concentration over time into a measure of exposure. A concentration at a single time point can provide a snapshot, whereas AUC represents the accumulated concentration-time profile over the period represented by the calculation. The registry describes the measure as AUC 0-∞ and says it reflects actual body exposure after administration of a dose. This definition specifies the intended endpoint, not its observed value.

The outcome description says plasma will be used to calculate the AUC. The registry record does not report the concentration measurements, the calculated AUC values, the mean, the standard deviation, or the number of participants contributing to the endpoint analysis. It also does not report the detailed computational procedure for deriving individual AUC estimates. Those methodological details are not reported in the registry record, so no additional assumptions about how they were handled can be made.

What can a single-group analysis show?

In general, a single-group study can describe measurements observed after an intervention in the participants studied. It has no concurrent comparator in this record, so it cannot isolate a difference between ketamine and a control condition through randomization. The allocation is listed as not applicable, masking as none, and the model as single group. These design features should guide interpretation of any descriptive measurements that may be reported.

The registry lists nine outcome measures but zero analyses. The primary endpoint’s summary type is specified, yet an analysis result is not. No confidence interval, p-value, adjusted estimate, or other inferential result is reported for the primary endpoint. In general, a confidence interval describes uncertainty around an estimate under specified assumptions; without a reported estimate and interval, the precision of AUC cannot be assessed. A p-value, when used, addresses compatibility of data with a specified null model under the analysis assumptions; no such value is reported.

How should planning calculations be understood?

The registry’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not results from the enrolled participants. They also describe a two-arm framework, unlike the single-group design recorded for Part 1. The registry record does not report the trial’s own sample-size justification.

In general, power calculations depend on assumptions about the effect to detect, variability, allocation, and the analysis. A planning calculation does not establish that an effect was observed, and changing the assumed effect changes the planning requirement. No values for particular planning scenarios are reported in the registry record used to describe this trial, so no scenario-specific sample-size interpretation is possible. The enrolled total of eight should not be confused with a calculated requirement or with a claim that the study had adequate power for a treatment comparison.

What is not described about the analysis?

The record does not report an analysis population, a missing-data approach, the number with complete pharmacokinetic profiles, or the handling of measurements below quantification limits. It also does not report whether there were planned covariate adjustments, sensitivity analyses, or interim analyses. These items are not reported in the registry record. They cannot be inferred from the endpoint definition or from the fact that the study is marked completed.

The description refers to breastmilk transfer, pharmacokinetic/pharmacodynamic assessments, and calculated estimates of neonatal and infant exposure. It does not supply numerical results or analysis details for those assessments. Part 2 is described as a larger randomized controlled trial with additional clinical outcomes, but those plans do not supply missing analysis methods or results for Part 1.

General statistical interpretation should therefore remain limited to what the record states: a single-group Phase 2 study enrolled eight participants, specified a continuous AUC endpoint summarized by mean and standard deviation, and lists no analyses. The endpoint’s intended meaning is clear, but its observed distribution, uncertainty, and any relationship to clinical outcomes cannot be evaluated from the reported numerical information.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Ketamine")
n   <- c(8)
m   <- c(28.46)
sp  <- c(9.97)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Ketamine  8  28.460  9.970  20.125  36.795

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, but the primary endpoint identified for this analysis is ketamine AUC during the 12 hour infusion. The record lists zero analyses and does not provide numerical results for that endpoint. It also does not report which of the other outcomes were analyzed, how outcomes were prioritized beyond the listed primary endpoint, or whether any multiplicity adjustment was planned or used. These details are not reported in the registry record.

In general, multiplicity arises when several hypotheses or outcomes are examined. Considering many results can increase the chance of finding an apparently notable result by chance, so statistical plans may specify how outcomes are prioritized or how inference is adjusted. That general issue does not establish that a particular adjustment was needed or performed in this study. No multiplicity procedure is reported in the registry record.

The record does not describe missing-data methods, the number of participants included in the primary endpoint analysis, or an analysis population such as all enrolled participants or participants with evaluable concentration measurements. Enrollment was eight, but the number contributing to each outcome is not reported. No assumptions about missing measurements, exclusions, or treatment of incomplete profiles should therefore be inferred.

Interim analyses and stopping rules are not reported in the registry record. Nor is a detailed statistical analysis plan reported. The status is completed, but completion status does not establish which analyses were conducted or how missing data and multiple outcomes were handled.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts for the ketamine group: eight participants at risk and zero affected. For other adverse events, eight participants were at risk and seven were affected. No serious adverse event terms are listed.

These figures are counts, not a comparison between ketamine and a control group. The study is single group and has no comparator, so the safety record cannot show whether the counts differ from what would have occurred under another treatment or without the intervention. The record also does not provide the event names for the other adverse events, their severity, timing, duration, or relationship to ketamine. Those details are not reported in the registry record.

In general, adverse-event counts describe events recorded in the participants observed; they do not by themselves establish causation. The limited cohort size and lack of a comparison group also constrain how broadly the counts can be interpreted. Zero serious adverse events recorded in this group should be read as the recorded count for this study, not as proof that serious events cannot occur.

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

The registry record describes a completed single-group Phase 2 study of intravenous ketamine after cesarean delivery, enrolling eight participants. Its primary endpoint is ketamine AUC during the 12 hour infusion, a measure intended to characterize plasma exposure over time. The endpoint definition and summary type are reported, but numerical AUC results are not.

As a result, the record does not establish the average exposure measured in the study or how much individual exposure varied. It does not provide a confidence interval or another uncertainty estimate for the primary endpoint. The record also does not provide a numerical clinical outcome result for pain, opioid use, postpartum depression, recovery, breastfeeding, or parent-infant bonding for this Part 1 analysis.

The study’s broader description includes breastmilk transfer and calculated neonatal and infant exposure estimates. These are stated objectives, but numerical findings for them are not reported in the registry record. The description of Part 2 refers to a larger randomized controlled trial with additional clinical outcomes; plans for that separate part should not be treated as results from Part 1.

The single-group design means there is no randomized comparator for estimating a treatment difference. The record can be read as documenting the study’s aims, design, endpoint definition, enrollment, and adverse-event counts. It cannot, on the information reported, establish a comparative effect, quantify clinical benefit, or determine the precision of the primary pharmacokinetic estimate.

The safety counts are also descriptive. The registry reports zero participants affected by serious adverse events among eight at risk, and seven affected by other adverse events among eight at risk. These counts do not show how event rates compare with another group, and the event details are not reported. They should not be extended beyond the participants recorded in this study.

In general, a result’s meaning depends on its estimate, uncertainty, design, and outcome definition. Here the design and intended endpoint are described, but the endpoint estimate and its uncertainty are missing. The appropriate interpretation is therefore limited: the registry record specifies what Part 1 aimed to measure, but does not report the numerical primary result needed to characterize observed ketamine exposure.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a pharmacokinetic endpoint and a clinical treatment comparison. Its primary endpoint, ketamine AUC, is intended to describe drug exposure over time. That is different from estimating whether a clinical outcome differs between treatment groups. The registry identifies the intended measurement clearly, while the single-group design makes clear that Part 1 is not a randomized comparison.

The study description also places the work in a broader program: Part 1 assesses pharmacokinetics/pharmacodynamics and breastmilk transfer, while Part 2 is described as a larger randomized controlled trial with clinical and recovery outcomes. Keeping these aims separate matters because the endpoint and design determine what conclusions an analysis can support. A drug-exposure measure does not itself answer questions about pain or recovery.

The registry reports enrollment of eight and lists nine outcome measures, but zero analyses and no numerical primary endpoint result. This makes the distinction between a protocol objective and a posted finding especially important. An outcome can be specified without its result being available in the record, and a completed status does not substitute for an estimate or an uncertainty measure.

Finally, the design and available safety counts illustrate why descriptive observations should not be read as comparative evidence. There is no control group, and adverse-event counts alone cannot establish whether the intervention changes risk. Statistically, the key contribution of the record is its description of the intended exposure measurement and study structure; its reported numerical information is insufficient to quantify the primary endpoint or compare outcomes.

15. 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 for interpreting the primary endpoint is that the registry record gives no numerical AUC result, despite specifying a mean and standard deviation as the intended summary. It also does not report a confidence interval, p-value, or other inferential result. The observed mean exposure and its precision therefore cannot be assessed.

The study enrolled eight participants and used a single-group, unmasked design with no comparator. These features limit the scope for comparative conclusions. The record does not state how many participants contributed to the primary endpoint, whether all enrolled participants had evaluable measurements, or how missing or incomplete measurements were handled.

Although the study description includes breastmilk transfer and calculated neonatal and infant exposure estimates, their numerical results are not reported in the registry record. The record also does not report detailed analysis methods, an analysis population, a sample-size justification, interim analyses, or a multiplicity procedure. Each of these details is not reported in the registry record and cannot be reconstructed from the study objective alone.

The safety information is limited to counts: eight participants at risk for serious adverse events with zero affected, and eight at risk for other adverse events with seven affected. Serious event terms are not listed, and details of other events are not reported. With no comparator, the counts do not provide a comparative safety estimate.

Part 2 is described as a separate, larger randomized controlled trial. Its planned outcomes and design do not resolve the limitations in the reported Part 1 results. Conclusions about the AUC estimate, clinical outcomes, or comparative effects require results that are not reported in this registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ketamine to Improve Recovery After Cesarean Delivery - Part 1 — NCT04037085.
• Registry record last updated 2022-12-20; status last verified 2022-11.
• Results first posted 2022-12-20.
• 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.

19. Record Summary

NCT04037085 is a completed Phase 2, single-group study of ketamine after cesarean delivery. It enrolled eight participants and lists no masking or randomized allocation. The intervention description specifies intravenous ketamine after cord clamping and a 12 hour infusion.

The primary endpoint is ketamine AUC during the infusion, measured in mcg*min/mL and intended to be summarized by mean and standard deviation. The registry record does not report numerical results for this endpoint and lists zero analyses. It describes Part 1 assessments of pharmacokinetics/pharmacodynamics, breastmilk transfer, and calculated neonatal and infant exposure estimates. Part 2 is described separately as a larger randomized controlled trial.

For safety, the record lists zero serious adverse events among eight at risk and other adverse events affecting seven of eight at risk. No serious event terms are listed. The record does not provide a comparator or the numerical primary endpoint findings needed to assess exposure or its precision.