Effectiveness of an Opioid Sparing Pain Regimen in Cardiac Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of an Opioid Sparing Pain Regimen in Cardiac Surgery (NCT03679013), a randomized phase 2 study. The primary outcome is The Number of Patients With Requests for Breakthrough Opioid Pain Medication in Opioid Standard of Care Regimen Compared to Non-opioid Multimodal Pain Relief Regimen (Experimental Group)..

2. Clinical Question

3. Trial Design

The registry record describes a Phase 2, randomized, open-label, parallel-group pilot study of postoperative pain regimens in cardiac surgery. The study summary identifies the setting as the Inova Heart and Vascular Institute and describes a single-center trial among patients who have undergone isolated coronary artery bypass graft surgery. The recorded enrollment is 19. The summary describes a study of 20 total patients, so the planned total and recorded enrollment are not the same.

Participants were assigned to an opioid-based standard-of-care regimen or an opioid-sparing regimen consisting of oral Gabapentin and intravenous Acetaminophen. Because the study was open-label, masking is listed as none. The registry record does not describe the randomization procedure, allocation concealment, or whether treatment assignment could be changed after assignment.

The primary endpoint is the number of participants requesting breakthrough pain medication, with a request defined by a pain score >4 on the Numeric Rating Scale. The stated assessment times are 24 hours, 48 hours, and 72 hours after treatment. The study summary also describes intended comparisons of pain scores, postoperative complications, and hospitalization costs. A secondary outcome listed in the record is the number of participants with ileus during hospitalization.

The study status is completed. The recorded start date is 2019-04-19 and the primary completion date is 2019-07-12. Completion status indicates the study is no longer ongoing; it does not by itself establish that outcome results or statistical analyses have been posted. Comparative endpoint estimates and analysis results are 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

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 The Number of Patients With Requests for Breakthrough Opioid Pain Medication in Opioid Standard of Care Regimen Compared to Non-opioid Multimodal Pain Relief Regimen (Experimental Group)., measured over 24 hours, 48 hours, 72 hours after post-surgical treatment.

The primary endpoint counts participants who request breakthrough opioid pain medication. The registry definition ties a request to a Numeric Rating Scale pain score >4. The scale is described as measuring pain intensity from 0-10, where 0 means no pain and 10 means the worst pain imaginable. The endpoint is assessed at 24 hours, 48 hours, and 72 hours after treatment.

This endpoint is intended to capture whether participants reach a level of reported pain associated with a request for additional medication. It is distinct from an average pain score: it records whether a participant meets the request criterion, rather than the magnitude of each score across the group. Counts can be useful for comparing how often a defined event occurs in each treatment group, but their interpretation depends on clear definitions, complete observation, and the way repeated assessment times are analyzed.

The registry record does not report the number of participants meeting this endpoint in either group at any of the assessment times. It also does not report a single combined endpoint across the times. Consequently, the endpoint definition can be described, but its observed comparative results cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint determine what statistical interpretation would be appropriate, but the registry record does not document the analysis methods used for the primary comparison. General explanations of those methods can clarify what the missing information would ordinarily help readers assess; they should not be read as a claim that any particular method was used in this study.

What does randomization contribute?

Randomization assigns participants to study groups using a chance-based procedure. In general, this helps make groups comparable with respect to factors that could affect outcomes, including factors that were not measured. It does not guarantee that small groups will be balanced on every characteristic. The registry record identifies the study as randomized but does not describe the sequence-generation process, allocation concealment, or any checks of baseline comparability.

The parallel-group design means participants are assigned to one regimen rather than being described as crossing between regimens. The open-label designation means masking is listed as none. General statistical interpretation should account for the fact that treatment awareness can affect participant reports, decisions to request medication, and clinical recording. The registry record does not describe whether outcome assessment or data analysis was masked.

How should a count endpoint be analyzed?

The primary outcome is a count of participants who meet a binary event definition: a request for breakthrough medication associated with a pain score >4. A comparison would ordinarily present the number meeting the definition and the number assessed in each group. An effect estimate could express the group contrast in a form suited to the question, with a confidence interval to show the range of values compatible with the data under the analysis assumptions. A confidence interval is not a guarantee that the true effect lies within its bounds; it conveys statistical uncertainty associated with the estimate.

The registry record does not provide the event counts, denominators at each time, effect estimates, confidence intervals, or p-values for this endpoint. It lists no analyses. No unadjusted recalculation can be made without the relevant summary statistics. In particular, the total enrollment and the safety denominators cannot be used as substitutes for the primary endpoint counts.

Why do the assessment times matter?

The endpoint is assessed at 24 hours, 48 hours, and 72 hours. Analyses at separate times can yield distinct estimates and uncertainty, because the event status and the number observed may vary across assessments. A model that considers repeated measurements could instead account for dependence among observations from the same participant. The registry record does not report whether measurements were treated as separate outcomes, analyzed jointly, or combined in another way.

When several related comparisons are made, the chance of at least one apparently unusual result can increase if each is interpreted independently without considering multiplicity. Methods for addressing this issue may include defining a primary time point in advance, adjusting inference, or treating time-specific analyses as exploratory. The record does not report a multiplicity plan, so it is not possible to determine how the study intended to handle the several assessment times.

What can planning illustrations tell readers?

The record describes planning assumptions for illustrations based on fractions of an observed effect: a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such calculations are conditional on the assumed effect and statistical model. They can show how a future design might be planned under those assumptions; they do not show the probability that this completed study detected an effect. That probability is often called power, and a planning calculation is not observed power.

The record explicitly distinguishes these illustrations from the study's own design. A sample-size justification for the original trial, the effect assumed in its planning, and the rationale for the stated enrollment are not reported in the registry record. Because the primary endpoint has several assessment times and no single comparison is reported, no single observed effect or study-specific planning conclusion can be inferred from the available endpoint information.

What remains unknown about analysis choices?

The registry record does not describe the statistical model, covariate adjustment, significance testing approach, handling of repeated measures, or sensitivity analyses. It also does not identify an analysis population, such as all randomized participants or participants with observed endpoint data. These choices matter because they define the population represented by an estimate and the assumptions used to calculate uncertainty. Without the analysis description and results, the study's statistical conclusions cannot be reconstructed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint has repeated assessment times at 24 hours, 48 hours, and 72 hours. The registry record notes that the outcome has several categories or time points and was not reduced to one comparison. It does not report a prespecified primary time point, a strategy for combining the assessments, or an adjustment for multiplicity. In general, interpreting several separate tests as if each were the only test can make chance findings more likely; whether and how that concern was handled in this study is not reported in the registry record.

The record does not report participant-level missingness, the number assessed at each time, reasons for missing observations, or methods for handling missing data. It is therefore not possible to determine whether the primary endpoint was available for every enrolled participant or whether incomplete follow-up could affect the comparisons. No imputation or sensitivity-analysis procedure is described.

The analysis population is also not reported in the registry record. It is unclear whether any planned analysis was to include all randomized participants, participants who received assigned treatment, or only those with available outcome data. These populations answer somewhat different questions and can produce different estimates.

No statistical analyses are listed in the registry record. This means there is no reported inferential result to evaluate for multiplicity, missing-data handling, or analysis-population choices. The reported enrollment and safety figures do not resolve these omissions for the primary endpoint.

11. 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.

The registry record lists 0 serious adverse events among 8 participants at risk in the opioid-based standard-of-care group and 0 among 11 participants at risk in the opioid-sparing group. It also lists 0 other adverse events in each group and 0 deaths in each group. No serious adverse-event terms are listed.

These figures describe the events recorded in the registry safety fields. They do not establish that no adverse events of any kind occurred, nor do they show that the regimens have equal safety. When no events are observed in a group, uncertainty about the underlying event rate remains, particularly in a small pilot study. The registry record does not provide confidence intervals or a comparative safety analysis.

The safety denominators are not the same as a full description of exposure or follow-up. The registry record does not report additional details about the safety-analysis population, adverse-event collection procedures, severity definitions beyond the serious and other categories, or how long each participant was observed for safety reporting. The study summary mentions postoperative complications as outcomes of interest, including ileus and respiratory measures, but the adverse-event figures alone do not provide results for those distinct clinical measures.

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

The registry record establishes that a randomized, open-label pilot study compared an opioid-based standard-of-care regimen with an opioid-sparing regimen of oral Gabapentin and intravenous Acetaminophen after cardiac surgery. It defines a primary outcome based on requests for breakthrough opioid medication and identifies assessment times after treatment. It also records adverse-event counts and a secondary outcome concerning ileus.

The record does not provide comparative primary endpoint results or statistical analyses. Therefore, it does not support a conclusion about the direction, size, or precision of any difference in requests for breakthrough medication. This lack of a posted estimate is not evidence that the regimens are equivalent, and it is not evidence that one regimen is superior. It is a limitation in what can be concluded from the registry record.

The pilot design and recorded enrollment describe a small study, but the available information does not establish its intended statistical power or the reason for the planned enrollment. The record's planning assumptions concern illustrations based on an observed effect and are not the original study's design justification. Such illustrations should not be treated as observed power or as confirmation of a treatment effect.

The safety fields report no serious or other adverse events and no deaths in either group, using the listed denominators. Those figures are descriptive and do not prove absence of risk or equivalence in safety. The study summary identifies outcomes such as pain scores, complications, and hospitalization costs, but comparative results for these outcomes are not reported in the registry record.

Overall, the available record is informative about the question the investigators set out to study and the broad design, but not about the comparative outcome findings. Statistical interpretation would require endpoint counts by group and time, denominators, an analysis plan, and estimates of uncertainty.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly described research question and a report that permits evaluation of its answer. The registry record specifies randomized allocation, parallel groups, an open-label design, and a threshold-based outcome related to requests for breakthrough medication. These details help define the intended comparison and the event being counted.

The endpoint is assessed repeatedly, which makes the analysis question important. A reader needs to know whether the investigators intended separate time-specific comparisons or an overall repeated-measures analysis, and how multiplicity was handled. The registry record does not report those choices. Without them, even a set of counts at individual times would need context before being interpreted as a single confirmatory result.

The study also illustrates why enrollment totals alone do not establish that a trial was adequately sized to answer its question. The recorded enrollment is 19, while the summary describes a planned total of 20. The original sample-size justification and the target effect are not reported in the registry record. Planning calculations based on observed effects are not a substitute for prospective design justification and should not be interpreted as observed power.

Finally, the safety figures are counts, not proof of equal risk. Zero recorded events in each group can be described accurately, while remaining cautious about what a small study can establish. For biostatisticians and clinical researchers, the central lesson is to separate design information, outcome definitions, observed results, and inferential conclusions. In this record, the first two are described more fully than the last two.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting efficacy is that comparative primary endpoint results are not reported in the registry record. There are no group counts for the defined breakthrough-medication outcome at 24 hours, 48 hours, or 72 hours, and no effect estimates, confidence intervals, or p-values. The registry record lists no analyses, so readers cannot assess the statistical evidence for a group difference.

The repeated assessment times create uncertainty about the intended estimand and multiplicity strategy. The record does not identify a single primary time point or explain whether time-specific results were to be combined. It also does not report missingness at each time, reasons for missing data, or an analysis population. These omissions prevent assessment of whether outcome availability or analysis choices could affect the findings.

The study is described as a pilot, with recorded enrollment of 19 and a planned total of 20 in the summary. The original sample-size rationale is not reported. Randomization is stated, but details of sequence generation and allocation concealment are not reported. The study is open-label, and the record does not say whether outcome assessment or analysis was masked. These details matter for judging the risk of bias in a participant-reported endpoint tied to a medication request.

The registry record does not describe the specific drugs or dosing in the opioid-based regimen, beyond identifying it as standard of care. The summary names several outcomes of interest, but their comparative results are not available in the information recorded. Safety counts are limited to the listed adverse-event categories and denominators, without reported uncertainty estimates or further collection details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of an Opioid Sparing Pain Regimen in Cardiac Surgery — NCT03679013.
• Registry record last updated 2022-11-08; status last verified 2022-10.
• Results first posted 2022-11-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03679013 is a completed Phase 2 randomized, open-label, parallel-group pilot study of postoperative pain regimens in cardiac surgery. The registry record identifies the setting as the Inova Heart and Vascular Institute and describes a comparison between an opioid-based standard-of-care regimen and oral Gabapentin paired with intravenous Acetaminophen. Recorded enrollment is 19; the study summary describes a planned total of 20.

The primary endpoint counts participants requesting breakthrough opioid pain medication under a pain-score threshold of >4, assessed at 24 hours, 48 hours, and 72 hours after treatment. The registry record does not report comparative results or statistical analyses for this endpoint. Safety fields list 0 serious adverse events, 0 other adverse events, and 0 deaths in both groups, with 8 participants at risk in the opioid-based group and 11 in the opioid-sparing group. These descriptive figures do not establish equal safety or absence of risk.