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 An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin in Treatment of Acute Headache (NCT04860713), a randomized phase 4 study. The primary outcome is Change in Pain Score at 60 Minutes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04860713 |
| Phase | Phase 4 |
| Condition | Pain |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Antonios Likourezos |
| Results posted | Yes |
2. Clinical Question
Population
Adults presenting to the emergency department with acute headache. The registry record reports enrollment of 5 participants, with outcome data listed for 4 participants in the AOK Group and 1 in the Nurtec (Rimegepant) Group.
Intervention
A proprietary oral formulation of ketamine at 0.85mg/kg combined with 324mg of aspirin, described as the AOK Group.
Comparator
Nurtec (rimegepant), described in the arm information as 75 mg of ODT.
Primary question
How did pain scores change from baseline to 60 minutes in each randomized group? The primary endpoint is the median change on the numeric rating pain scale. Although the registry record identifies two arms, it does not report a statistical estimate or test comparing their outcomes.
The trial concerns acute headache treatment in an emergency-department setting. Its primary question is framed around change in pain score rather than a final score alone. Comparing change from baseline can describe how scores shift over the stated follow-up interval, but a group-level comparison needs an analysis that accounts for the observed data and the uncertainty around the estimates. The registry record does not report such a comparative estimate, confidence interval, or p-value. The recorded medians therefore describe the posted arm-level results; they do not by themselves establish whether the groups differ.
3. Trial Design
The registry record classifies this as a phase 4, randomized, open-label, parallel-group clinical trial. Participants were assigned to one of two drug groups: the AOK Group, receiving a proprietary oral formulation of ketamine plus aspirin, or the Nurtec (Rimegepant) Group. Masking is listed as none, so the trial is open label. The registry record identifies adults presenting to the emergency department with acute headache as the population of interest.
Enrollment is recorded as 5. For the primary outcome, the registry lists 4 participants in the AOK Group and 1 in the Nurtec (Rimegepant) Group. Those arm counts are important when interpreting the descriptive results: a median based on a very small group can be strongly affected by individual observations, and a single participant's score represents the entire posted Nurtec group. These data do not support a stable estimate of how outcomes might vary across a broader population.
The trial is marked completed. Its start date is 2021-04-22 and its primary completion date is 2022-09-30. The registry record does not report the randomization procedure, allocation concealment, eligibility criteria beyond the stated population, or details about treatment administration beyond the listed formulations. It also does not report a protocol-level statistical analysis plan or sample-size justification. Those omissions prevent a fuller assessment of how the trial was designed to address potential sources of bias or how the planned analysis relates to the posted 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.
Overall Study
| Stage | AOK Group | Nurtec (Rimegepant) Group |
|---|---|---|
| STARTED | 4 | 1 |
| COMPLETED | 4 | 1 |
| NOT COMPLETED | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | AOK Group | Nurtec (Rimegepant) Group | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 1 | 5 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 1 | 5 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 3 | 1 | 4 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 1 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Pain Score at 60 Minutes, measured over 60 minutes.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in pain score at 60 minutes. The registry describes it as the change from baseline on the numeric rating pain scale, with the result summarized as a median and full range for each group. The scale is an 11 item Likert Scale from 0, meaning no pain, to 10, meaning very severe pain; 5 indicates moderate pain. A change score represents the difference between a participant's baseline score and score at the stated follow-up, though the registry record does not specify the direction convention used for calculating change.
Pain scores are commonly summarized with medians when the aim is to describe the center of observed scores without relying on a mean-based summary. Reporting the full range also conveys the lowest and highest observed changes in each group. These descriptive statistics can make the recorded observations easier to interpret, but they do not provide a measure of precision or quantify a between-group difference. The registry record does not report confidence intervals for this endpoint.
A 60-minute assessment defines a specific follow-up point for the primary outcome. It does not, on its own, describe pain beyond that point. The record lists one outcome measure and does not report secondary outcomes. Because the direction convention for change is not stated, the reported medians should be read as the recorded changes, without assuming whether a positive value represents improvement or worsening.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a median change in pain score of 4, with a full range from 0 to 8, for the AOK Group. For the Nurtec (Rimegepant) Group, it reports a median change of 5, with a full range from 5 to 5. These are arm-level descriptive results at the 60-minute endpoint. The record does not state the direction convention for change scores, so the values should not be labeled as reductions or increases in pain without further information.
The posted arm sizes are 4 participants for AOK and 1 participant for Nurtec. With only one participant in the Nurtec group, its reported median and range describe that participant's result rather than a well-characterized distribution of responses. In the AOK group, the median and range summarize a few observations, so both are sensitive to individual results. The reported ranges convey observed spread, not the uncertainty around a population-level estimate.
No comparative effect estimate, confidence interval, or p-value is reported in the registry record. As a result, the recorded medians cannot establish the size or precision of a difference between groups. The record lists no analysis entries, and it does not explain whether any planned comparative analysis was conducted but omitted or whether it could not be estimated. A skipped two-arm comparison is noted for another endpoint; that note does not supply a comparative result for the primary endpoint.
These data are best read as a sparse descriptive record rather than a definitive evaluation of relative effects. Randomization is part of the design, but the small and unequal posted arm sizes, open-label status, and absence of a reported comparative analysis constrain what can be concluded. The record also does not provide information about baseline pain scores by group, so the starting distributions cannot be assessed from the posted outcome summary alone.
The registry reports no serious adverse events, other adverse events, or deaths in either group. Those are counts observed in the listed safety groups, not proof that the treatments carry no risk. The small number of participants means uncommon events would be difficult to characterize. Overall, the posted results describe what was recorded for this trial, while leaving substantial uncertainty about comparative outcomes and safety beyond those observations.
9. Statistical Methods Explained
The registry record describes a randomized, parallel-group comparison and summarizes the primary endpoint using medians and full ranges. These are descriptive statistics: they organize the observed results within each arm. They do not, by themselves, estimate a treatment contrast or indicate how uncertain that contrast is. The endpoint is change in pain score at 60 minutes, measured on the stated numeric rating pain scale.
What does a median describe?
In general, the median is the middle observation after values are ordered. It is a measure of the center of a distribution and is less influenced by extreme values than the arithmetic mean. The registry reports a median of 4 for AOK and 5 for Nurtec. Because the Nurtec outcome group contains 1 participant, its median is simply that participant's recorded value. The AOK median is based on 4 participants. Neither arm's median should be treated as a precise estimate of the typical response in a broader patient population.
A full range gives the lowest and highest recorded values. The AOK range is 0 to 8, while the Nurtec range is 5 to 5. A range is useful for describing the observed endpoints, but it does not show how values are distributed between them. It also is not a confidence interval. With few observations, the range can change considerably if another participant's result is added.
What would a comparative estimate add?
In general, a comparative analysis summarizes the difference between groups and quantifies uncertainty around that estimate. A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level; its width conveys precision. A p-value, when used, measures how compatible the observed data are with a specified null model. Neither measure replaces clinical judgment, and neither can be reconstructed reliably from arm medians and ranges alone. The registry record does not report a comparative estimate, confidence interval, or p-value for the primary endpoint.
Random allocation can support a fair comparison when implemented as planned, but it does not guarantee similar groups in a very small trial. In general, randomization balances measured and unmeasured factors across groups over repeated assignments, not necessarily in every individual trial. The registry record does not report the randomization method or allocation concealment, so those implementation details cannot be assessed. The groups are also markedly unequal in their posted outcome counts, limiting the information available for a comparison.
How should the design features be considered?
The trial is open label, with masking listed as none. In general, awareness of assigned treatment can influence participant-reported outcomes, expectations, co-interventions, or assessment. Pain scores are reported by participants, so the lack of masking is relevant when considering possible measurement and expectation effects. The registry record does not describe procedures intended to address these possibilities.
The endpoint is a change from baseline. In general, change scores combine information from baseline and follow-up and can be affected by starting values and measurement variability. The record does not report baseline scores by arm, the calculation direction, or details of how missing observations were handled. Those details matter for interpreting change and for evaluating whether the outcome summaries represent all randomized participants.
What do the planning assumptions mean?
The registry's planning framework is described as an illustration based on the observed effect, not as the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such sample-size calculations are planning illustrations, not observed power and not evidence that a study has established an effect. The registry record does not report the trial's own sample-size justification, and no planning estimates should be interpreted as results from participants.
These methods distinctions are particularly important. The posted medians and ranges are observations, while any inference about a population-level difference would require an analysis and uncertainty measure that the registry record does not report. No recalculated comparative result is available in the record. There is therefore no sponsor analysis to compare with a recalculation, and the observed summaries should remain descriptive.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure, identifies change in pain score at 60 minutes as the primary endpoint, and lists no secondary outcomes. It records no analysis entries. No multiplicity adjustment or plan for handling multiple statistical tests is reported in the registry record. With no reported set of statistical tests, it is not possible to assess how multiplicity was addressed in an analysis.
The outcome population field is blank, and the registry record does not describe the analysis population, such as whether results include all randomized participants or only those with an available measurement. It does not report the number of missing baseline or follow-up scores, reasons for missingness, or any imputation method. The posted arm counts for the primary outcome are 4 for AOK and 1 for Nurtec, while overall enrollment is recorded as 5. The record does not explain the relationship between enrollment and endpoint availability.
In general, missing outcome data can affect both the summary of observed scores and the validity of a comparison, particularly when missingness is related to participants' outcomes or treatment. An analysis population and missing-data approach clarify which observations contribute and the assumptions used. Because these details are not reported in the registry record, it is not possible to determine whether missing data influenced the posted summaries or whether any sensitivity analysis was undertaken.
The registry record also does not report an interim-analysis plan, stopping rules, or a protocol-level statistical analysis plan. No assumptions should be made about those procedures. The absence of these details is a reporting limitation, not evidence that a particular analysis or procedure did or did not occur.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| AOK Group | 0 | 4 | 0.0% |
| Nurtec (Rimegepant) Group | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| AOK Group | 0 of 4 |
| Nurtec (Rimegepant) Group | 0 of 1 |
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 |
|---|---|
| AOK Group | 0 of 4 |
| Nurtec (Rimegepant) Group | 0 of 1 |
The registry reports 0 serious adverse events and 0 other adverse events in the AOK Group, with 4 participants listed at risk for each category. For the Nurtec (Rimegepant) Group, it reports 0 serious adverse events and 0 other adverse events, with 1 participant listed at risk for each category. Deaths are recorded as 0 in both groups.
These figures describe events recorded during the trial for the listed safety groups. They do not establish that adverse events cannot occur. In general, when few participants are observed, the absence of recorded events provides limited information about the frequency of uncommon harms. The registry record does not report the safety follow-up duration, event definitions, or additional detail about how adverse events were collected. Serious event terms are not listed.
The safety counts should be interpreted alongside the small group sizes and the limited information about follow-up. They are not comparative estimates of safety, and the registry record does not report a statistical analysis of adverse events. The lack of recorded events in these groups should not be extended beyond the participants and observation described by the registry.
12. What the Result Does, and Does Not, Mean
The posted results establish what the registry record reports for the primary endpoint: median change in pain score at 60 minutes was 4, with a full range of 0 to 8, in the AOK Group, and 5, with a full range of 5 to 5, in the Nurtec (Rimegepant) Group. They also establish the listed arm sizes and safety event counts. These are descriptive observations from a randomized, open-label trial.
They do not establish a precise between-group effect. No comparative estimate, confidence interval, or p-value is reported for the primary endpoint. In addition, the record does not specify the direction convention for change, making it inappropriate to interpret the positive values as improvement or worsening. A median from the Nurtec group represents one participant's recorded outcome, while the AOK summary is also based on a very small group.
The results do not establish how outcomes would vary in a larger or different population, or what might happen beyond the 60-minute assessment. The record does not provide baseline scores by group, analysis-population details, missing-data methods, or a fuller statistical analysis plan. It also does not report longer-term outcomes. These gaps make it difficult to assess the robustness and generalizability of the recorded summaries.
Likewise, the recorded absence of adverse events and deaths does not show that either treatment has no risks. The safety groups are small, and the record does not describe follow-up duration or event-collection details. The reasonable statistical reading is narrow: the registry documents a small set of arm-level outcome and safety observations, but does not provide enough inferential information to determine a reliable comparative effect or to characterize safety beyond those observations.
13. Why This Trial Matters Statistically
This trial illustrates the difference between reporting observations and supporting a statistical comparison. The record identifies a randomized design and reports an outcome for each arm, but the outcome groups are very small and unequal. A median and range can describe the recorded results; they cannot substitute for an estimate of the difference between groups or its uncertainty. That distinction matters whenever a reader encounters a numerical result without a corresponding inferential analysis.
The endpoint also highlights the importance of clear outcome definitions. Change from baseline is meaningful only when the direction of subtraction and the relevant analysis population are understood. The registry record names the time point and scale but does not state the direction convention, provide baseline scores by group, or explain missing-data handling. Those omissions leave key interpretive questions open even when the arm-level medians and ranges are available.
Open-label status is another statistical consideration, especially for a participant-reported pain outcome. In general, awareness of treatment assignment can affect reported outcomes. That possibility does not prove bias occurred, but it is part of assessing how confidently the observed values can be attributed to treatment assignment. The registry does not describe masking or other measures to limit expectation effects.
Finally, safety counts with no recorded events need careful framing when the observed groups are small. Zero observed events is a factual description of this record, not a guarantee about future risk. Taken together, these features make the trial useful as an example of why study design, transparent analysis methods, and uncertainty estimates are essential alongside outcome summaries. The record's limitations should constrain the strength of conclusions drawn from its numerical results.
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.
Several limitations are specific to the information recorded for this trial. The registry lists enrollment of 5, while the primary-outcome results are listed for 4 participants in the AOK Group and 1 in the Nurtec (Rimegepant) Group. The record does not explain whether these counts reflect missing follow-up, exclusions, or another reason. It does not report baseline pain scores by arm, so the starting levels cannot be compared from the posted results.
The primary endpoint is described as change from baseline at 60 minutes, but the direction convention is not reported. The outcome population is not specified, and details of missing data and analysis populations are not reported in the registry record. No confidence interval, p-value, or comparative effect estimate is listed. These omissions prevent assessment of precision and make the arm-level summaries difficult to interpret as a comparison.
The trial is open label, and the outcome is based on participants' pain ratings. The registry record does not describe procedures to reduce possible expectation or assessment effects. It also does not report the randomization procedure, allocation concealment, detailed eligibility criteria, or the trial's own sample-size justification. Protocol-level statistical methods, including any interim analysis plan, are not reported in the registry record.
For safety, the record lists no adverse events or deaths, but does not report follow-up duration, event definitions, or collection procedures. These limits, together with the small and unequal posted outcome groups, mean that neither comparative effectiveness nor the frequency of uncommon adverse events can be characterized precisely from this registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin in Treatment of Acute Headache — NCT04860713.
- Registry record last updated 2024-01-31; status last verified 2022-11.
- Results first posted 2024-01-31.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed phase 4, randomized, open-label, parallel-group trial of oral ketamine plus aspirin versus Nurtec (rimegepant) in adults presenting to the emergency department with acute headache. Enrollment is recorded as 5.
The primary endpoint is change in pain score at 60 minutes on a numeric rating scale from 0 to 10. The AOK Group has a reported median change of 4 and full range of 0 to 8, based on 4 participants. The Nurtec (Rimegepant) Group has a reported median change of 5 and full range of 5 to 5, based on 1 participant. The registry record does not report the direction convention for change or a comparative statistical analysis.
No serious adverse events, other adverse events, or deaths are recorded in either group. The record lists no secondary outcomes or analysis entries. Important details about missing data, analysis populations, precision estimates, and the trial's statistical plan are not reported in the registry record.