US Guided GNB vs Saline Injection for TKA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for US Guided GNB vs Saline Injection for TKA (NCT03316118), a randomized phase 4 study. The primary outcome is Post-operative Opioid Consumption During the Hospital Stay.

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, double-masked, parallel-group trial sponsored by Northwestern University. It compares a genicular nerve block with bupivacaine against normal saline administered as the nerve block. The study title specifies ultrasound guidance and total knee replacement. The registry describes the trial as terminated. The reason for termination is not reported in the registry record.

Enrollment was 2. Both subjects were randomized to Group 1, which received the bupivacaine intervention; Group 2 had no enrolled subjects. Randomization therefore did not result in observed participants in both comparison groups. Although the planned allocation ratio and details of how randomization was implemented are not reported in the registry record, the absence of a saline group in the enrolled sample is clear from the posted arm counts.

The primary outcome was postoperative opioid consumption during the hospital stay, measured in morphine milligram equivalents through 36 hours after surgery. The registry lists secondary outcomes concerning mean knee pain at rest during the first 48 hours after surgery, satisfaction with pain control at 72 hours after surgery, and length of hospitalization. Results for those secondary outcomes are not reported in the registry record.

The registry gives a study start date of 2017-10-05 and a primary completion date of 2021-06-21. It does not report who was masked, how masking was maintained, or the planned analysis approach. The posted record includes no analyses. These design features describe the registered plan and available results, but they do not establish that the planned comparison was carried out successfully.

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: Only two subjects enrolled both were randomized to group 1.

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: Study terminated early due to low enrollment.

6. Primary Endpoint

The registry lists the primary outcome as Post-operative Opioid Consumption During the Hospital Stay, measured over 36 hours after surgery.

The primary endpoint measures postoperative opioid consumption during the hospital stay, up to 36 hours after surgery. Consumption is expressed in morphine milligram equivalents, a common scale for representing opioid amounts on a shared measurement basis. The registry specifies the outcome as a mean and reports the full range for the group with results.

Opioid consumption is included because the study's stated hypothesis links the intervention to lower opioid use, alongside reduced systemic side effects and improved satisfaction. The primary endpoint directly describes medication consumption over a defined postoperative period. It is not itself a direct measure of pain intensity, satisfaction, or adverse effects; those are separate outcomes or considerations in the study description.

Group 1's posted mean is 24.17 MME, with a full range from 23.0 to 27.2. Group 2 has no enrolled subjects and no reported endpoint value. Consequently, the endpoint record describes consumption in the bupivacaine group but cannot quantify a difference between bupivacaine and saline. The registry does not report an uncertainty interval or a comparative estimate for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcome is a group-level descriptive summary: a mean and full range for opioid consumption in Group 1. No comparative analysis is reported. The explanations below describe general statistical concepts and how they relate to the information in the registry record; they do not imply that any unreported method was used in this trial.

What does the mean describe?

Generally, a mean is calculated by adding observed measurements and dividing by the number of measurements. It gives a compact description of the center of the observed values. Here, the reported mean is 24.17 MME for Group 1. A mean does not show every subject's measurement, and it can be affected by unusually high or low observations. The record reports the full range, from 23.0 to 27.2, which gives the lowest and highest observed values as represented in the posted summary. It does not report a standard deviation or another measure of variability around the mean.

A range is easy to interpret but depends only on the endpoints of the observed values. It does not describe how values are distributed between those endpoints. The range also tends to depend on the number of observations: with few observations, it may give a limited picture of the variation that could occur in a wider population. In this trial, the enrolled sample is very small, so the mean and range should be understood as summaries of those observations, not stable estimates for all patients undergoing total knee replacement.

Why is there no treatment contrast?

Generally, a two-group trial estimates a contrast by comparing an outcome summary for the intervention group with the corresponding summary for the comparator group. Randomization is intended to make the groups comparable on average, reducing bias from systematic differences in group assignment. But the comparison still requires observed outcome information in both groups. Here, both enrolled subjects were randomized to Group 1 and none to Group 2. Thus the record has no saline-group mean to compare with the bupivacaine-group mean. The treatment contrast is not estimable from the posted results.

Without a contrast, an inferential test cannot establish whether the observed group values are compatible with chance variation under a specified null hypothesis. Nor can a confidence interval quantify uncertainty around a bupivacaine-versus-saline difference. In general, a confidence interval is a range of values generated by a statistical procedure intended to express uncertainty about an estimated quantity. It does not guarantee that the true value lies in that range, and it cannot be constructed for a group contrast that the posted data do not estimate. No p-value or confidence interval for the primary comparison is reported in the registry record.

What role would a statistical model play?

Generally, a model can account for the outcome's distribution, study design, or other features of the data. For example, count outcomes with variability greater than a basic count model expects may require a method that allows over-dispersion. This is a general consideration, not a description of this trial's endpoint or an analysis that the registry says was used. The primary outcome is reported as a mean in MME, and the registry does not report a model, a variance estimate, an adjusted analysis, or a statistical analysis plan. It is therefore not possible to assess whether a particular model was selected or whether model assumptions were evaluated.

Likewise, adjustment for baseline characteristics can sometimes improve precision or address chance imbalance in randomized studies. The registry record does not report baseline characteristics, covariate adjustments, or an adjusted treatment estimate. With no enrolled subjects in the comparator group, adjustment would not supply the missing observed saline outcome. Statistical modeling cannot replace the absent comparison data.

How should sample-size illustrations be understood?

Generally, a sample-size calculation describes how many participants a future study might need under specified assumptions about the effect to detect, the significance level, allocation, and analysis. Such a calculation is a planning illustration, not an observed finding and not a measure of the probability that the completed trial detected an effect. The record describes assumptions for planning illustrations, including a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of an observed effect. However, the posted trial results do not contain an observed two-group effect because Group 2 has no enrolled subjects. The registry does not report the trial's own sample-size justification. No planning illustration should be read as evidence of observed power or as a replacement for a comparative result.

In general, a larger sample can improve precision when the design and data support the intended analysis, but sample size alone does not correct bias or create a missing comparator. Here, the key obstacle is not merely imprecision around an estimated contrast: the contrast itself is unavailable from the posted group results. The registry's zero analysis entries and the missing two-arm comparison are consistent with treating the primary outcome as descriptive only.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: mean knee pain at rest during the first 48 hours after surgery, satisfaction with pain control at 72 hours after surgery, and length of hospitalization. Their outcome results are not reported in the registry record. No analysis results are posted for the primary or secondary outcomes, and the record does not provide a statistical analysis plan describing how these outcomes were to be analyzed.

Multiplicity arises generally when several outcomes or hypotheses are tested. If many tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the number and role of the tests. A prespecified hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses can help readers interpret multiple results. The registry does not report whether any such approach was planned. Since comparative results and analyses are not posted, it is not possible to assess how multiplicity was handled.

Missing information needs careful interpretation. Group 2 had no enrolled subjects, so its absent endpoint value is not a missing measurement among enrolled Group 2 participants; there were no such participants in the record. Instead, there is no observed comparator group from which to estimate a contrast. For Group 1, the registry reports a mean and full range, but does not report individual measurements or describe any missing outcome data. It is not reported in the registry record whether all planned assessments were completed or how missing observations, if any, were handled.

The record also does not define the analysis population, such as whether results were intended to follow an intention-to-treat or per-protocol approach. Such labels describe which randomized participants are included in an analysis and under what rules. They cannot be inferred from the posted summary. In this record, the reported endpoint describes Group 1 only, and the lack of a comparator result prevents a randomized two-arm analysis regardless of the population label.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

Safety counts in the registry are reported separately by group. In Group 1, 0 participants were affected by a serious adverse event among 2 at risk; the reported death count is 0. The record also reports 1 participant affected by an other, non-serious adverse event among 2 at risk. The registry does not provide a term describing that event. Group 2 has 0 participants at risk and reports 0 serious events, 0 other adverse events, and 0 deaths.

These figures should not be read as a meaningful safety comparison between interventions. Group 2 had no enrolled subjects, so its zeros reflect the absence of a group at risk in the posted record, not observed experience among saline recipients. The Group 1 counts describe only the small enrolled group. A count of zero serious events in that group does not establish that serious events cannot occur or that the intervention is safer than saline.

Generally, adverse-event counts depend on the number of participants observed, the duration and completeness of follow-up, and how events are defined and collected. Those details are not reported in the registry record beyond the displayed at-risk counts and event counts. The serious-event figures are therefore a limited description of recorded events, not a comparative safety estimate or a basis for drawing broader conclusions.

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

The posted results establish that the registry reports a primary opioid-consumption summary for Group 1: a mean of 24.17 MME and a full range from 23.0 to 27.2, measured during the hospital stay up to 36 hours after surgery. They also establish that both enrolled subjects were randomized to Group 1 and that Group 2 had no enrolled subjects. These registry entries describe the available record.

They do not establish how opioid consumption would differ between a genicular nerve block with bupivacaine and saline. A comparative effect requires information from both groups, and the registry provides no observed endpoint value for the saline group. There is no reported treatment difference, confidence interval, p-value, or analysis result for the primary endpoint. The Group 1 mean cannot serve as a stand-in for the missing comparator outcome.

The result also does not answer the separate questions about knee pain at rest, satisfaction with pain control, length of hospitalization, or systemic side effects. Secondary outcomes are listed, but their results are not reported in the registry record. The one reported other adverse event and the absence of recorded serious adverse events in Group 1 are small-sample descriptive counts; they do not provide a comparative safety assessment.

Generally, a randomized design can support causal comparisons when it yields adequate outcome information in the assigned groups and the analysis follows an appropriate plan. Randomization alone does not guarantee that a useful comparison can be estimated. In this record, assignment did not produce an observed saline group. The registry does not report the reason the trial was terminated, so the enrollment pattern cannot be attributed to any particular cause.

Accordingly, the posted information is best understood as a limited descriptive record of outcomes in the bupivacaine group. It neither demonstrates a comparative benefit nor demonstrates a lack of benefit. It does not support a conclusion about what would happen in a broader population or under a different study design.

13. Why This Trial Matters Statistically

This trial illustrates a basic requirement of comparative research: each group in the intended contrast needs outcome information. Randomization is an important design feature, but it does not by itself ensure that a treatment effect can be estimated. Here, the registry records a randomized design but reports that both enrolled subjects were assigned to Group 1 and none to Group 2. The gap between the planned comparison and the available group results determines what can be learned statistically.

The example also shows why descriptive summaries should be separated from comparative evidence. The mean and range convey information about opioid consumption in the observed bupivacaine group. They do not quantify a difference from saline. Treating a single-group mean as though it were a treatment effect would confuse an observed outcome level with a contrast between interventions.

Small enrollment also limits how much can be learned about variability and generalizability. A mean and range can accurately describe the posted observations while still providing little precision about outcomes in a wider population. Statistical uncertainty is not removed by reporting a point estimate. In this case, uncertainty around a treatment contrast cannot be quantified because no contrast is available in the posted results.

Finally, the registry distinguishes outcomes that are often discussed together but measure different things. Opioid consumption, pain scores, satisfaction, hospitalization duration, and adverse events are not interchangeable measures. The record names several of these outcomes, but only the primary endpoint has a posted group summary. Reading each result in relation to its own definition, observed data, and missing information helps prevent conclusions that exceed the evidence.

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 trial-specific limitation is the absence of an enrolled comparator group. Although the registry describes a randomized comparison of bupivacaine and saline, both enrolled subjects were assigned to Group 1 and Group 2 had none. A between-group effect cannot be estimated from these posted results. The reason for this allocation pattern and the reason for termination are not reported in the registry record.

The enrolled sample is very small, limiting the descriptive and inferential information available even for Group 1. The reported mean and range give a summary, but the record does not include a confidence interval, standard deviation, or individual outcome values. It is not reported in the registry record whether all planned assessments were completed or whether the posted endpoint summary includes all intended observations.

The registry does not report analysis methods, a statistical analysis plan, the definition of the analysis population, or any inferential results. It does not describe who was masked, how masking was implemented, or whether the planned design was changed. The registered secondary outcomes have no reported results, and the record does not explain why they are absent. The reason for trial termination is also unreported.

Safety interpretation is similarly constrained. Group 1 has a recorded other adverse event, but its description is not given; the absence of serious events in this small group does not establish comparative safety. Group 2 has no participants at risk, so its event counts cannot be compared with Group 1. These limitations apply to the registry record and do not establish what may have occurred outside the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: US Guided GNB vs Saline Injection for TKA — NCT03316118.
• Registry record last updated 2022-09-28; status last verified 2022-09.
• Results first posted 2022-09-28.
• 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.

18. Record Summary

The registry describes a Phase 4, randomized, double-masked, parallel-group trial of ultrasound-guided genicular nerve block with bupivacaine versus saline for total knee replacement. The trial was sponsored by Northwestern University and is listed as terminated. The reason for termination is not reported in the registry record.

Enrollment was 2, with both subjects randomized to Group 1. The primary outcome was postoperative opioid consumption through 36 hours after surgery, expressed in MME. Group 1's reported mean was 24.17, with a full range from 23.0 to 27.2. Group 2 had no enrolled subjects, so a comparison with saline is unavailable. Results for the listed secondary outcomes are not reported in the registry record, and the registry reports no analyses.