Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients (NCT03431285), a randomized na study. The primary outcome is Pain Scores.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group trial comparing a ketamine regimen with a morphine regimen for acute painful crisis in sickle cell disease. The registry lists the phase as not applicable. Both groups were also assigned standard intravenous hydration. The drug infusions were each described as lasting 30 minutes, with the doses and diluent specified separately for each group.

The registry records enrollment of 278 and lists 140 participants in the morphine group and 138 in the ketamine group for the posted primary outcome. The primary outcome population is identified as intention to treat. The record does not explain how that population was defined for this trial, whether all randomized participants contributed outcome data, or how missing outcome measurements were handled.

The recorded study start date is 2018-01-01, the primary completion date is 2019-01-10, and the status is completed. The sponsor is Imam Abdulrahman Bin Faisal University. The registry record does not report the study location, participant demographics, eligibility criteria, allocation concealment procedures, or the identities of the people included in triple masking. Those omissions limit what can be inferred about trial conduct and the population to which the results may apply.

Pain scores were scheduled every 30 minutes for a maximum of 180 minutes. The primary outcome is described as the mean difference in numerical pain rating scale score over three hours. Listed secondary outcomes cover emergency-department length of stay, cumulative opioid use, hospital admission, and drug-related adverse effects. Their stated measurement windows differ, so they address related but not identical aspects of the acute-care episode.

The record contains posted outcome summaries but no reported analysis details. It does not describe the planned statistical model, any interim analyses, the original sample-size justification, or procedures for controlling false-positive findings across outcomes. The registry record also does not specify whether the masking was maintained throughout follow-up or how protocol deviations were handled.

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: intention to treat (ITT)

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: Intention to treat

6. Primary Endpoint

The registry lists the primary outcome as Pain Scores, measured over NPRS will be recorded every 30 minutes for a maximum of 180 minutes..

The primary endpoint is mean pain score on the numerical pain rating scale over three hours. The scale ranges from 0, meaning no pain, to 10, meaning the worst pain. The registry says scores would be recorded every 30 minutes for a maximum of 180 minutes and describes the endpoint as a mean difference between groups. It identifies the primary population as intention to treat.

Pain scores are used to quantify a patient-reported symptom on a consistent scale. Repeated measurement during the acute-care period can describe how scores change over time, while a group mean provides a concise summary for comparison. A mean difference expresses the average separation between groups in the scale’s units. It does not show the full distribution of individual scores, how many participants improved, or whether changes were important to patients.

The posted arm summaries give mean scores of 5.6 for morphine and 5.7 for ketamine, with standard deviations of 1.9 and 2.13, respectively. The unadjusted recalculation from those summaries estimates a mean difference of 0.1 for ketamine relative to morphine. The registry does not report a threshold for a clinically important change, or a detailed method for combining repeated scores into the three-hour endpoint. Interpretation should therefore remain tied to the reported scale, summary, and measurement window.

7. Results Posted in the Registry

• Ketamine Group: mean 5.70 versus 5.60 on control; difference 0.10 (95% CI -0.37 to 0.57), standardized effect d = 0.05; z-test p = 0.680.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Length of Stay in ED

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ketamine Group: mean 4.70 versus 4.80 on control; difference -0.10 (95% CI -0.63 to 0.43), standardized effect d = -0.04; z-test p = 0.709.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ketamine Group and the control. The interval gives the range of effects that remain compatible with the data.

Cumulative Use of Opioid

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ketamine Group: mean 0.07 versus 0.13 on control; difference -0.06 (95% CI -0.08 to -0.04), standardized effect d = -0.65; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ketamine Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The Rate of Hospital Admission

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ketamine Group: 18.8% (26/138) versus 24.3% (34/140) on control; risk difference -5.4 percentage points (95% CI -15.1 to 4.2), risk ratio 0.78 (0.49–1.22); unadjusted two-proportion z-test p = 0.270.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ketamine Group and the control. The interval gives the range of effects that remain compatible with the data.

Across the secondary outcomes, the posted pattern is not uniform. The unadjusted opioid-use comparison shows clearer statistical separation than the other secondary comparisons. The emergency-department stay and hospital-admission comparisons have results that leave uncertainty around the direction of a group difference. This means that the secondary outcomes do not all reinforce one another in a single, consistent pattern.

The opioid-use outcome relates to the investigators’ stated hypothesis about narcotic requirement, while the primary endpoint directly measures pain scores. A difference in opioid use does not by itself establish a corresponding difference in pain, and the primary result does not settle the separate question of opioid consumption. Emergency-department stay and admission describe aspects of care and disposition; they are not substitutes for the primary symptom measure. Each endpoint addresses a distinct question within the acute-care period.

These are secondary comparisons, and the registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting them. When several outcomes are tested, the chance of at least one apparently notable result can increase. Unadjusted p-values do not account for that broader testing context. As a result, secondary findings generally carry less weight than a clearly prespecified primary comparison unless the trial’s analysis plan explains how they were to be interpreted.

The record lists four secondary outcomes and contains no reported analysis details. It does not state whether every listed outcome was analyzed as planned, whether there were additional analyses, or how missing values were handled for each endpoint. The posted secondary data can describe the observed pattern, but they cannot establish the investigators’ full inferential approach. The most defensible reading is to treat the secondary results as supportive context rather than as independent confirmation of a broad treatment effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Length of Stay in ED
• Cumulative Use of Opioid
• The Rate of Hospital Admission
• Drug-related Adverse Effects

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score, and the registry summarizes it using a mean and standard deviation. A mean describes the center of the observed scores, while a standard deviation describes how spread out individual scores are around that mean. These summaries help characterize each group, but they do not show the shape of the score distribution or how each participant’s score changed across repeated measurements.

What does the mean difference represent?

The mean difference compares the average score in one group with the average score in the other. The posted summaries give 5.6 for morphine and 5.7 for ketamine. The unadjusted recalculation gives a mean difference of 0.1 for ketamine relative to morphine. The sign indicates which group has the higher mean under that comparison order; for a pain score, a higher score corresponds to more pain on the stated scale. A group mean difference does not imply that every participant experienced a change of that size.

The recalculation is unadjusted because it uses the posted group summaries rather than individual participant data or a model adjusting for other factors. It is a useful way to describe the numerical contrast, but it cannot account for participant-level features, the correlation among repeated scores, or details of the analysis plan that are not reported. The registry record lists no reported analyses, so the exact method used by the trial investigators is not reported in the registry record.

Why is uncertainty reported with an interval?

A confidence interval describes a range of values compatible with the data under the statistical method and its assumptions. For a difference between means, an interval that includes zero leaves open the possibility of no average difference as well as differences in either direction. Its width conveys precision: a narrower interval is more precise than a wider interval, all else being equal. A confidence interval is not a guarantee that the true effect lies within its endpoints, and it does not itself determine whether a difference matters clinically.

The primary comparison has an interval that crosses zero, alongside an unadjusted p-value of 0.68. The p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the calculation assumptions held. It is not a probability that the null hypothesis is true, and it is not a measure of effect size. The interval and p-value answer related but distinct questions: the interval displays a range of estimates and their precision, while the p-value summarizes evidence against a null value under a test.

Why can over-dispersion matter?

For count or event outcomes, the variability may be greater than a simple model expects. This is called over-dispersion. If a model assumes less variability than the data contain, standard errors can be too small, intervals too narrow, and p-values too optimistic. This is a general statistical consideration; the registry record does not describe a count-data model for these outcomes, and no over-dispersion assessment is reported.

The pain endpoint is a score rather than an event count, so over-dispersion is not the main issue for its mean comparison. Other concerns are more directly relevant: the record describes repeated score collection, but does not state how the measurements were combined, whether an average over time or a particular timepoint was analyzed, or how within-participant correlation was handled. No adjustment or repeated-measures model is reported in the registry record.

What do the secondary comparisons add?

The secondary outcomes include continuous measures and a binary admission outcome. Continuous outcomes are summarized by group means and standard deviations, then compared using a mean difference in the unadjusted recalculations. The admission outcome is a count of participants meeting a yes-or-no endpoint. Its comparison is expressed as a risk difference, which contrasts the groups’ event proportions. In general, a risk difference expresses an absolute difference in event probability; it is not the same quantity as a relative risk or odds ratio.

These secondary comparisons were recalculated from posted summaries and are not a substitute for trial-level models using individual data. The registry record does not report adjustment for baseline characteristics, missing outcomes, or multiplicity. The posted p-values are unadjusted. Without a stated analysis plan, readers cannot determine whether these comparisons were prespecified, whether additional analyses were performed, or how the investigators intended to weigh the multiple endpoints.

What is not described about the analysis?

The primary outcome specifies intention to treat, but the record does not report the detailed analysis population or participant flow. It does not specify how missing scores were handled, whether all randomized participants contributed to each outcome, or how protocol deviations were treated. The original statistical plan, sample-size justification, interim analyses, and adjustment for repeated measurements are also not reported in the registry record. These omissions constrain assessment of the reliability and reproducibility of the posted analyses.

General statistical interpretation requires separating the observed estimate from its uncertainty, the p-value from clinical importance, and the posted summary calculation from the investigators’ full analysis. No discrepancy is flagged between the recalculations and sponsor analysis in the registry record. That does not add unreported details about the sponsor’s statistical methods; those methods remain unreported.

11. Confidence Intervals and Precision

The primary mean-difference estimate is 0.1, and its confidence interval extends both below and above zero. The interval therefore includes values consistent with a lower mean score in either group, as well as no difference. The unadjusted p-value is 0.68. These features indicate that the posted primary summaries do not precisely establish the direction of a difference. The interval is more informative than the point estimate alone because it shows the uncertainty surrounding that estimate.

Precision is not the same as clinical importance. A narrow interval can still include effects that matter little, while a wider interval can include both small and more consequential effects. The registry record does not state a threshold for a clinically important difference on the pain scale, so the interval cannot be judged against a trial-defined benchmark. Nor does the mean difference describe how much scores varied between individuals; the group standard deviations are 1.9 and 2.13.

The secondary outcomes have differing levels of precision. The opioid-use comparison has a confidence interval that does not cross zero and an unadjusted p-value below 0.001. The intervals for emergency-department stay and hospital admission cross the null value for their respective comparisons. Those distinctions describe statistical uncertainty, not the certainty of a clinical conclusion. Because the secondary outcomes are unadjusted and the multiplicity plan is not reported in the registry record, their p-values should not be treated as if they were the sole planned test.

Confidence intervals depend on the statistical method and assumptions used to calculate them. The registry record does not report the investigators’ full methods, the handling of missing data, or any model for repeated measurements. The intervals discussed are unadjusted recalculations from posted summary statistics. They describe the precision of those comparisons, not every uncertainty about trial conduct, data collection, or applicability to other settings.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning estimates for the primary pain-score comparison are expressed as participants per arm, not as a total across arms. For 80% power, the estimates are 6,390 participants per arm when planning for 100% of the observed effect, 11,359 when planning for 75% of the observed effect, and 25,557 when planning for 50% of the observed effect. For 90% power, the corresponding estimates are 8,554, 15,206, and 34,213 participants per arm.

Power is the chance, under a specified design and effect assumption, of detecting an effect using the chosen statistical test if that effect is the true one. The 80% column describes a planning target with an 80% chance of detecting the assumed effect; the 90% column uses a higher chance of detection and therefore requires more participants under these assumptions. Planning for a smaller effect requires more participants because a smaller separation between groups is harder to distinguish from random variation.

The listed illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect is the stated fraction of the observed effect. These are planning illustrations based on the observed effect, not the original trial design assumptions; the original design assumptions are not reported in the registry record. This is not observed power.

For the non-time-to-event planning figures, the unit is participants per arm; time-to-event planning figures, if present, would instead use total events. The primary-outcome estimates are large because the observed mean difference is small relative to the variability in pain scores. These estimates are sensitive to the observed effect used as the planning basis and should not be read as evidence that the trial was designed to recruit those numbers.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.100; pooled standard deviation σ = 2.017.
2. n = 2 × (1.96 + 0.842)² × 2.017² / 0.100² = 6,389.1, rounded up to 6,390 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.100000000000001                      # observed difference in means
sigma <- 2.01744681879515                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3431285)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 6,390 (80% power), 8,554 (90% power)
 75% of observed effect: n per arm = 11,359 (80% power), 15,206 (90% power)
 50% of observed effect: n per arm = 25,557 (80% power), 34,213 (90% power)
power.t.test: 6390.1 
Simulated power at n = 6,390 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, timepoints, or analyses are examined. Even when each statistical test uses the same nominal threshold, performing many tests increases the chance that at least one result will appear notable by chance. Methods such as family-wise error control or false-discovery-rate procedures can address different versions of this problem. These are general statistical approaches; the registry record does not say that any such method was planned or used.

The record identifies one primary outcome and four secondary outcomes. Pain scores were scheduled repeatedly during the three-hour measurement period, but the record does not explain how those repeated measurements entered the primary analysis or whether each timepoint was tested separately. The statistical plan, any outcome hierarchy, and any adjustment across outcomes or timepoints are not reported in the registry record. The unadjusted secondary p-values should therefore be interpreted cautiously and should not be treated as confirmatory evidence without that context.

The primary outcome population is described as intention to treat. That label generally refers to analyzing participants according to randomized assignment, but the record does not give the operational definition used in this trial. It does not report participant flow by outcome, missing-data amounts, reasons for missingness, imputation procedures, or sensitivity analyses. It is not possible to determine from the registry record whether missing scores could have influenced the posted comparisons.

The registry record lists no reported analyses. The planned model, any adjustment for baseline factors, the treatment of protocol deviations, interim analyses, and the investigators’ approach to repeated measures are not reported. Nor is the original sample-size justification reported. These are important gaps for assessing whether the posted results follow a prespecified plan and whether the uncertainty estimates reflect the actual data structure.

Missing analysis information does not show that the trial methods were inadequate; it means that the registry record does not document them. Interpretation should distinguish that documentation gap from evidence about the actual conduct of the trial. The posted summaries permit descriptive and unadjusted comparisons, but they do not answer questions that require individual-level data or a full statistical analysis plan.

15. 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 zero serious adverse events in the morphine group and zero in the ketamine group. It also reports zero deaths in each group. The listed numbers at risk for the serious-event summaries are 140 for morphine and 138 for ketamine. These are event counts in the posted record; they do not establish that serious events were impossible or that the regimens have identical safety profiles.

The record does not provide definitions of serious adverse events, details of how events were collected or adjudicated, or a statistical comparison for these counts. It also does not report follow-up duration for the serious-event summary. The absence of reported serious events should therefore be read as a feature of the posted data, not as proof of no risk. Other adverse effects are listed separately, but the registry record does not provide enough detail to assess their nature, severity, timing, or relationship to treatment.

Safety interpretation depends on the event definitions, ascertainment methods, and duration of observation, as well as on the number of participants observed. Those details are not reported in the registry record. The posted serious-event counts are limited evidence about safety and should not be extended beyond what the record documents.

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

The primary data describe similar group means for the pain-score endpoint during the specified acute-care observation period. The unadjusted mean difference is small in magnitude, its confidence interval crosses zero, and its p-value is 0.68. This does not establish a clear difference in mean pain score, but it also does not show that the two regimens are equivalent. Equivalence would require a prespecified margin and an analysis designed to assess whether the full uncertainty lies within that margin; neither is reported in the registry record.

The secondary results address different outcomes. The unadjusted opioid-use comparison is more statistically distinct than the primary pain-score comparison, while emergency-department stay and hospital admission remain uncertain in their group contrasts. These outcomes cannot be combined informally into a single conclusion about overall benefit. The registry record does not state how the investigators planned to weigh different outcomes or whether the secondary tests were adjusted for multiple comparisons.

The numbers apply to the participants and time windows represented in the posted record. Pain was assessed for up to 180 minutes, opioid use for three hours following admission to the emergency department, emergency-department stay for five hours following admission, and hospital admission within three hours following study enrollment. The record does not report longer-term pain, later clinical outcomes, or a clinically important threshold for the pain scale.

The findings are statistical descriptions, not medical advice. They do not establish that either regimen should be selected for an individual, and they do not establish that one is broadly superior or that the regimens have the same effects. The registry record does not provide the details needed to assess every aspect of trial conduct, missing data, or analysis. The appropriate scope is the posted comparison, its uncertainty, and the stated outcome windows.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate should not be interpreted without its uncertainty. The primary group means are close, but the confidence interval spans values on both sides of no difference. A single estimate cannot show how precisely the comparison is known, and a non-small p-value does not prove that effects are identical. The interval and the absence of a reported clinical-importance threshold leave separate questions about statistical precision and practical meaning.

It also illustrates why outcomes should be interpreted separately. Pain score, opioid consumption, length of emergency-department stay, and hospital admission measure different dimensions of acute care. A comparatively distinct result for one secondary endpoint does not automatically determine the result for the primary endpoint. Distinguishing those outcomes helps avoid treating a multi-outcome study as if it had one simple, all-purpose conclusion.

The registry record also demonstrates the importance of transparent analysis reporting. The primary population is named, but the analysis method, missing-data handling, multiplicity plan, and original sample-size justification are not reported. Without those details, readers can describe the posted summaries and their unadjusted uncertainty, but cannot fully evaluate how the investigators intended to analyze repeated scores or interpret the set of outcomes.

Finally, planning estimates based on an observed effect are not a retrospective measure of whether a trial was adequately powered. They depend on assumptions about the effect worth detecting and the design. Keeping planning illustrations separate from observed trial results prevents a common misinterpretation of power and sample-size calculations.

18. 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 posted primary outcome is summarized as a mean score, while the registry describes repeated measurement every 30 minutes for a maximum of 180 minutes. The record does not state whether the mean represents a particular timepoint, an average across time, or another summary of the repeated scores. It also does not report a repeated-measures analysis or how correlation among scores from the same participant was handled. This limits interpretation of the endpoint’s exact construction.

The registry record identifies an intention-to-treat population but does not explain its operational definition or report missing-data handling. Participant flow for each endpoint, reasons for missing measurements, and sensitivity analyses are not reported. The posted group summaries may not reveal how missing observations or protocol deviations affected the analyses.

Interpretation of secondary findings is limited by the lack of a reported multiplicity strategy and analysis hierarchy. The registry lists several outcomes, but does not document whether they were all prespecified for confirmatory testing or how their results were intended to be combined. The secondary comparisons are unadjusted recalculations from posted summaries, so they do not account for potential baseline differences or other participant-level factors.

Generalizability is difficult to assess because eligibility criteria, participant demographics, study location, and clinical setting details beyond the emergency-department outcome windows are not reported in the registry record. The observed pain outcome is limited to the acute three-hour period, and longer-term outcomes are not reported. A clinically important difference threshold for the pain scale is also not reported.

Finally, the record does not provide the original sample-size rationale, detailed statistical plan, interim-analysis information, allocation-concealment procedures, or the identities of those masked. These omissions do not establish that the trial lacked such procedures; they limit what can be assessed from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients — NCT03431285.
• Registry record last updated 2025-05-28; status last verified 2025-05.
• Results first posted 2025-05-28.
• 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.

22. Record Summary

The registry record describes a completed, randomized, triple-masked, parallel-group trial of ketamine versus morphine for acute painful crisis in sickle cell disease. Both groups were assigned standard intravenous hydration. Enrollment was 278, and the posted primary outcome lists 140 participants in the morphine group and 138 in the ketamine group. The primary endpoint was mean numerical pain score over three hours, with the scale ranging from 0 to 10.

The posted primary means were 5.6 for morphine and 5.7 for ketamine. The unadjusted recalculation gives a mean difference of 0.1, with an interval that crosses zero and an unadjusted p-value of 0.68. Secondary outcomes cover emergency-department stay, opioid use, hospital admission, and adverse effects. Their unadjusted results vary, and the registry record does not report a multiplicity plan or detailed analysis methods.

The record lists zero serious adverse events and zero deaths in each group. Important details about missing data, repeated-measures analysis, clinical-importance thresholds, and the original sample-size justification are not reported in the registry record. The findings should be interpreted as posted summaries with these uncertainties and documentation limits.