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 Dronabinol in Total Knee Arthroplasty (TKA) (NCT04734080), a randomized phase 4 study. The primary outcome is Cumulative Opioid Consumption 24-48 Hours Post-operatively.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04734080 |
| Phase | Phase 4 |
| Condition | Total Knee Arthroplasty, Opioid Use |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 114 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hospital for Special Surgery, New York |
| Results posted | Yes |
2. Clinical Question
Population
Participants undergoing primary total knee arthroplasty were the target population. The registry record describes the condition as total knee arthroplasty and opioid use. The primary outcome record notes that participants were lost to follow up or withdrawn, but does not report further eligibility details or the characteristics of those participants.
Intervention
The intervention was dronabinol, described in the arm record as 5 mg given twice daily, beginning on the day of surgery and ending with the morning dose on POD2. The brief summary describes dosing as starting in the immediate preoperative period for enrollment before 1 PM, so the registry record contains differing descriptions of the start time.
Comparator
The comparison group received an oral placebo. Its arm description gives the same twice-daily schedule, beginning on the day of surgery and ending with the morning dose on POD2. The study is recorded as randomized, with a parallel-group model.
Primary question
The primary question was whether perioperative dronabinol changed cumulative opioid consumption, measured in morphine milligram equivalents, during the stated 24-48-hour postoperative period. The primary outcome description says measurement began at recovery room entry and ended 48 hours after anesthesia stop time. The registry also lists questions about pain, hospital stay, physical therapy goals and oxygen desaturation, but these are secondary to the stated primary outcome.
3. Trial Design
The registry record describes a randomized, parallel-group phase 4 trial of dronabinol versus placebo in people undergoing primary total knee arthroplasty. The enrollment figure is 114. The planned arm descriptions each specify 57 subjects, while the posted primary outcome records 55 participants in the dronabinol group and 56 in the placebo group. These figures describe different parts of the record; the reason for the difference is not reported in the registry record.
The intervention descriptions specify twice-daily dosing of 5 mg dronabinol or a non-active placebo, beginning on the day of surgery and ending with the morning dose on POD2. The brief summary instead says that dronabinol begins in the immediate preoperative period for enrollment before 1 PM. The registry record does not reconcile these descriptions. Masking is recorded as triple, while the brief summary calls the trial double-blinded; further detail about who was masked is not reported in the registry record.
The study is listed as completed. Its recorded start date is 2021-03-09 and its primary completion date is 2023-10-06. Hospital for Special Surgery, New York, is listed as the sponsor. The registry identifies opioid consumption as the primary outcome and lists secondary outcomes covering pain, physical therapy, hospital length of stay, oxygen desaturation, and pain-related questionnaires. The number of outcome measures is 19, and the record lists 18 secondary outcomes. A fuller account of the recruitment process, protocol deviations, and the analysis population is not reported in the registry record.
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 | Dronabinol | Placebo |
|---|---|---|
| STARTED | 57 | 57 |
| COMPLETED | 55 | 56 |
| NOT COMPLETED | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants were lost to follow up/withdrawn.
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 | Dronabinol | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 55 | 56 | 111 | |
| Age, Continuous | years | 62 (58 to 66) | 63 (58 to 66) | 63 (58 to 66) |
| Sex: Female, Male: Female | Participants | 32 | 26 | 58 |
| Sex: Female, Male: Male | Participants | 23 | 30 | 53 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 | 5 | 9 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 48 | 50 | 98 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 3 | 1 | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 3 | 2 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 2 | 8 |
| Race (NIH/OMB): White | Participants | 44 | 48 | 92 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 4 | 6 |
| American Society of Anesthesiologists (ASA) Class: 1 | participants | 0 | 1 | 1 |
| American Society of Anesthesiologists (ASA) Class: 2 | participants | 54 | 53 | 107 |
| American Society of Anesthesiologists (ASA) Class: 3 | participants | 1 | 2 | 3 |
| Body Mass Index | kg/m^2 | 30.9 (28.0 to 34.3) | 29.3 (27.6 to 33.9) | 29.8 (27.8 to 34.3) |
6. Primary Endpoint
The registry lists the primary outcome as Cumulative Opioid Consumption 24-48 Hours Post-operatively, measured over 24-48 hours post-operatively.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | morphine milligram equivalents |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is cumulative opioid consumption measured in morphine milligram equivalents during the 24-48-hour postoperative period. The outcome description defines the measurement window as starting at recovery room entry and ending 48 hours after anesthesia stop time. Morphine milligram equivalents express opioid consumption on a common scale, allowing different opioid medicines to be summarized using a shared unit.
The registry reports this endpoint using the median and inter-quartile range. The median describes the middle of the observed values after ordering them; the inter-quartile range describes the spread of the central portion of those values. In general, medians and inter-quartile ranges can be useful when measurements are skewed or include unusually high values, because they are less sensitive to extremes than the mean and standard deviation. The registry record does not state why this summary was selected.
The endpoint is relevant to the trial’s stated question because it directly quantifies opioid consumption over a defined postoperative period. Its interpretation is limited to that measure and time window: it does not by itself describe pain, function, later opioid use, or the balance of benefits and harms. The registry record’s primary outcome population field says participants were lost to follow up or withdrawn, but does not give further detail about handling missing primary outcome measurements.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results give a median cumulative opioid consumption of 8 morphine milligram equivalents in the dronabinol group and 15 in the placebo group. The reported inter-quartile range is 7.5 to 30 for each group. The registry reports a Wilcoxon (Mann-Whitney) comparison with p = 0.27. These results describe the recorded sample; they do not establish that the groups differ in the wider population.
The medians are separated in the observed data, but the reported p-value does not provide strong statistical evidence against the null comparison under the test used. A p-value is a measure of how compatible the observed data are with a specified null model, assuming that model and the test’s assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry does not report a confidence interval or a numerical effect estimate for the primary comparison, so the precision of the between-group contrast cannot be assessed directly from those quantities.
The identical reported inter-quartile ranges do not mean that the group distributions are identical. They describe only the central spread, and the medians describe only their centers. Individual observations, other distribution features, and the test result all contribute to interpretation. The Wilcoxon test is rank-based and evaluates the relative ordering of observations; it is not simply a test of whether the reported medians are equal in every possible distribution.
The primary outcome record has 55 participants in the dronabinol group and 56 in the placebo group. The arm descriptions had specified 57 for each group. The record notes loss to follow up or withdrawal for the primary outcome population, but does not explain the participant flow or whether missing outcomes were handled using a particular method. That missing information limits assessment of whether the analyzed observations represent the randomized groups without important bias.
The result should therefore be read narrowly: the registry reports lower observed median opioid consumption in the dronabinol group, with a Wilcoxon p-value of 0.27 and no reported primary confidence interval. It does not establish a statistically clear group difference, and the available record does not show how precise the contrast is or how missingness might affect it.
9. Statistical Methods Explained
The primary comparison is reported as a Wilcoxon (Mann-Whitney) test. This is a rank-based method for comparing two independent groups. Rather than relying on the group means, it orders the observations and compares their ranks. In general, this can be useful when outcome values are skewed or when a small number of large values could strongly affect a mean-based comparison. The registry record does not report diagnostic checks or explain why this method was selected.
What does the Wilcoxon test assess?
In general, the Mann-Whitney procedure tests whether values in one group tend to be higher or lower than values in the other, under its null formulation. It can be interpreted as a test of a location shift only under additional distributional assumptions, such as similarly shaped group distributions. It is not automatically a test of the difference between medians alone. This distinction matters because the posted results summarize each group with a median and inter-quartile range, while the p-value comes from a rank-based comparison using the observations.
The registry reports p = 0.27 for the primary comparison. In general, a p-value is calculated under a null hypothesis and the assumptions of the analysis. A larger p-value indicates that the observed data are not unusual under that null model; it does not prove that the groups are the same. Nor does a p-value convey the magnitude of an effect or the range of effect sizes compatible with the data. A confidence interval for a between-group estimate would help show precision, but one is not reported for the primary analysis in the registry record.
Why report medians and inter-quartile ranges?
In general, the median is resistant to extreme observations, and the inter-quartile range describes the middle spread of the data. These summaries are often useful for consumption outcomes that may have a skewed distribution. The posted medians are 8 and 15 morphine milligram equivalents, and the inter-quartile ranges are 7.5 to 30 in both groups. Equal inter-quartile ranges do not establish equal distributions: the summaries omit detail about values within and outside that central interval. The registry record does not report the full distribution or a rationale for its chosen summary statistics.
How should the secondary recalculation be understood?
A recalculated risk difference is a simple, unadjusted comparison based on the posted counts. For the postoperative day 90 opioid-consumption outcome, the recalculated confidence interval spans zero, and the unadjusted p-value is 0.171. In general, a confidence interval that includes zero for a difference is compatible with no difference as well as with effects in either direction, at the interval’s stated confidence level. The record does not report a sponsor analysis for this secondary outcome, and this recalculation does not adjust for other comparisons.
Unadjusted analyses consider each comparison separately. When many outcomes or comparisons are examined, the chance of observing an apparently unusual result by chance can increase. In general, multiplicity procedures can account for a family of related tests, but no multiplicity strategy is reported in the registry record. The secondary results should therefore be treated as exploratory unless a prespecified analysis plan establishes otherwise; that plan is not reported in the registry record.
What can planning illustrations tell the reader?
In general, a sample-size planning illustration asks how many participants per arm would be needed under specified assumptions to detect an effect of a chosen size with a target power and significance level. The assumptions listed for the illustrations use the observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation. Such values are planning illustrations, not observed power, and do not establish that the trial was designed around those assumptions. The registry record does not report the trial’s own sample-size justification, prespecified target effect, or power calculation.
For the primary endpoint, the registry lists 55 and 56 analyzed participants by arm, while the arm descriptions specify 57 per arm. The reason for this difference, the handling of missing outcomes, and the details of the analysis population are not reported in the registry record. Those omissions matter because the interpretation of a randomized comparison depends on how participants are retained and how unavailable measurements are addressed.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wilcoxon (Mann-Whitney) | not reported | 0.270 |
The registry reports the sponsor’s primary comparison using the Wilcoxon (Mann-Whitney) method, with p = 0.27. It reports the group medians and inter-quartile ranges but does not report a primary effect estimate or confidence interval. No recalculated primary contrast is reported in the registry record, so there is no independent primary recalculation to compare with the sponsor’s stated test result.
The available secondary risk-difference calculation is unadjusted and is based on posted summary counts. Its confidence interval includes zero, and its unadjusted p-value is 0.171. It addresses a secondary outcome, not the primary opioid-consumption comparison, and should not be treated as a replacement for the sponsor’s primary analysis. The record does not flag a discrepancy between a sponsor result and a recalculation.
In general, a simple recalculation can help readers check a comparison from posted summaries, but it may not reproduce an analysis that uses individual-level data, covariate adjustment, or other specified procedures. The registry record does not describe such additional procedures for the primary comparison. The sponsor’s reported primary analysis remains the relevant recorded analysis; the lack of an effect estimate and confidence interval leaves its precision less fully characterized.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists 19 outcome measures, including 18 secondary outcomes, and 114 analyses. It does not report a multiplicity plan. When a study assesses many outcomes or conducts many comparisons, the probability of at least one apparently unusual result can rise even if there is no underlying effect. In general, prespecifying a primary outcome and analysis helps distinguish the main confirmatory question from supplementary analyses. Adjustment methods can also be used when a defined family of tests is intended to support joint conclusions. The record does not say whether any such method was planned.
The primary outcome population is described as participants who were lost to follow up or withdrawn. The primary outcome results are recorded for 55 participants in the dronabinol group and 56 in the placebo group, while the arm descriptions specify 57 participants per group. The reason for the difference, the number and timing of missing measurements, and the approach to missing data are not reported in the registry record. No imputation method, sensitivity analysis, or complete-case rationale is reported.
In general, missing outcome data can affect a group comparison if the likelihood of missingness is related to the outcome or differs between groups. The direction and size of any resulting bias depend on why data are missing and on the analysis method. Without participant-flow details and missing-data analyses, the extent of this concern cannot be assessed from the registry record.
The record does not report the primary analysis population definition, such as whether participants were analyzed according to randomized assignment, or the handling of protocol deviations. It also does not report interim analyses, stopping rules, a statistical analysis plan, or the trial’s sample-size justification. These omissions limit assessment of whether the reported analyses followed a prespecified plan and how much confidence to place in secondary comparisons.
12. 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 |
|---|---|---|---|
| Dronabinol | 0 | 55 | 0.0% |
| Placebo | 0 | 56 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dronabinol | 0 of 55 |
| Placebo | 0 of 56 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dronabinol | 0 of 55 |
| Placebo | 0 of 56 |
The posted safety counts report zero serious adverse events and zero other adverse events in the dronabinol group, with 55 participants at risk, and zero serious adverse events and zero other adverse events in the placebo group, with 56 participants at risk. Deaths are recorded as zero in each group. The registry lists no serious adverse event terms.
These figures describe events recorded in the registry for the stated groups; they do not show that an event is impossible or that the treatments have identical safety profiles. In general, zero observed events in a study does not rule out events that are uncommon, occur outside the observation period, or were not captured or reported. The registry record does not report the safety follow-up duration, event-collection procedures, or additional detail on adverse-event definitions.
The counts should be read alongside the size and scope of the study and the limitations of its safety reporting. They are not a comprehensive estimate of safety for every setting or patient group. They also do not establish a difference between the groups; no comparative safety analysis is reported in the registry record.
13. What the Result Does, and Does Not, Mean
The primary result describes opioid consumption in this randomized trial among participants with posted primary outcome data. The dronabinol group had a median of 8 morphine milligram equivalents and the placebo group had a median of 15, with an inter-quartile range of 7.5 to 30 for each group. The registry reports p = 0.27 from a Wilcoxon (Mann-Whitney) comparison. This combination describes the observed sample but does not establish a clear between-group difference.
A p-value above a conventional threshold is not proof that the groups are equivalent. Equivalence or non-inferiority requires a prespecified margin and an analysis designed to assess that question; such a margin or analysis is not reported in the registry record. Conversely, the separation between the observed medians alone does not establish a reliable treatment effect. The primary comparison has no reported confidence interval or effect estimate in the registry record, which limits evaluation of precision.
The result applies to the measured opioid-consumption endpoint and its specified postoperative window. It does not, by itself, answer whether pain, mobility, length of stay, later opioid consumption, or adverse events differ. Secondary outcomes can add context, but the record does not report a multiplicity strategy, and a complete pattern of secondary estimates and uncertainty is not available.
In general, statistical evidence and clinical importance are different questions. A statistically detectable difference may be small in practical terms, while an uncertain estimate may still include effects that could matter. The registry does not state a threshold for a clinically important change in opioid consumption, so the clinical importance of the observed median separation cannot be determined from the reported summary alone.
The findings should not be generalized beyond the trial population and setting without further evidence. The registry record does not provide enough detail about missing outcomes, participant characteristics, or the analysis population to fully assess that generalizability. The result is best understood as a report of the observed data and the sponsor’s stated test, not as a definitive conclusion about treatment effect.
14. Why This Trial Matters Statistically
This trial raises a useful statistical question because postoperative opioid consumption is a quantitative outcome that can be summarized in different ways. The registry uses medians and inter-quartile ranges and reports a rank-based comparison. That pairing makes it important to distinguish a descriptive summary of group centers from the statistical question addressed by the test. Readers should not assume that a rank-based p-value tests only the difference between the two reported medians.
The observed medians differ, but the reported p-value is 0.27 and no primary confidence interval is available. This illustrates why effect size and precision are both important: a descriptive difference does not by itself show how stable or uncertain the contrast is. A confidence interval could communicate a range of effects compatible with the data, while a p-value alone does not provide that range.
The record also highlights the importance of transparent participant flow. The arm descriptions specify 57 participants per group, whereas the primary outcome results include 55 and 56. Without a clear account of missing measurements and analysis populations, readers cannot determine how those differences arose or assess possible missing-data bias.
Finally, the registry lists a broad range of secondary outcomes and analyses. In general, multiple comparisons complicate interpretation unless outcomes and analysis priorities are prespecified and multiplicity is addressed. The record does not describe such a plan. The trial is therefore a reminder that a clear primary analysis, complete uncertainty estimates, transparent missing-data reporting, and careful handling of secondary questions are all needed to interpret clinical trial evidence.
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 registry record does not report a primary effect estimate or confidence interval, so the precision of the primary group contrast is difficult to judge. The group medians and inter-quartile ranges provide useful descriptive information but do not show the full distribution of opioid consumption or the range of plausible between-group effects.
Participant accounting is not fully explained. The arm descriptions specify 57 participants in each group, while the primary outcome records 55 and 56. The record notes loss to follow up or withdrawal in the primary outcome population but does not explain the reasons, timing, or handling of missing measurements. The analysis population and any sensitivity analyses are not reported.
The registry’s dosing descriptions differ on when treatment began: the brief summary refers to the immediate preoperative period for enrollment before 1 PM, while the arm descriptions state that dosing began on the day of surgery. The masking information is also described differently: the registry field says triple masking, while the brief summary calls the trial double-blinded. The record does not clarify these differences.
The registry does not report a statistical analysis plan, a sample-size justification, an interim-analysis plan, or a multiplicity strategy. These gaps limit assessment of prespecification and the confirmatory status of secondary findings. The record lists many secondary outcome areas, but a complete interpretation of their estimates and uncertainty is not possible from the available results. Safety counts are reported, but the follow-up period and event-collection details are not.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Dronabinol in Total Knee Arthroplasty (TKA) — NCT04734080.
- Registry record last updated 2026-03-27; status last verified 2025-01.
- Results first posted 2026-03-27.
- 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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19. Record Summary
NCT04734080 is a completed, randomized, parallel-group phase 4 trial sponsored by Hospital for Special Surgery, New York. It compared perioperative dronabinol with placebo in participants undergoing primary total knee arthroplasty. The recorded study start date is 2021-03-09, and the primary completion date is 2023-10-06.
The primary endpoint was cumulative opioid consumption in morphine milligram equivalents during the stated 24-48-hour postoperative period. The reported medians were 8 for dronabinol and 15 for placebo, with inter-quartile ranges of 7.5 to 30 in both groups. The Wilcoxon (Mann-Whitney) p-value was 0.27; a primary confidence interval and effect estimate are not reported in the registry record.
The record lists secondary outcomes spanning pain, physical therapy, hospital stay, oxygen desaturation, and questionnaires. It reports zero serious adverse events, zero other adverse events, and zero deaths in each group. Missing-data handling, multiplicity procedures, and the trial’s statistical analysis plan are not reported in the registry record.