Efficacy of Botulinum Toxin Injections in the Rectus Femoris to Treat Stiff Knee Gait Following Acquired Brain Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Botulinum Toxin Injections in the Rectus Femoris to Treat Stiff Knee Gait Following Acquired Brain Injury (NCT00900666), a randomized na study. The primary outcome is Mean Peak Knee Flexion During Swing Phase of Gait.

2. Clinical Question

The trial asks whether gait measures differ between people with acquired brain injury and stiff knee gait who receive botulinum toxin A (BTX-A) injection to the rectus femoris and those who receive saline injection to the same muscle. Its primary question concerns mean peak knee flexion during the swing phase of gait. The registry also identifies questions about peak knee velocity during preswing and initial swing, and gait function based on the 6-Minute Walk and temporal-distance measures.

The stated rationale is that stiff knee gait involves reduced knee flexion during swing and can affect foot clearance, walking efficiency, speed, and compensatory movement. Those descriptions establish why gait is studied; they are not findings from this trial. The registry record does not report the measured group values, an estimated between-group difference, confidence intervals, or a test result. Therefore, the listed research questions cannot be answered from the posted outcome information.

3. Trial Design

The record describes a randomized, double-masked, parallel-group trial. Participants were assigned to botulinum toxin injection to the rectus femoris or saline injection to the rectus femoris. Random allocation can help balance measured and unmeasured participant characteristics between groups on average, while masking can reduce some opportunities for expectations to influence care or assessment. The registry does not report how the random sequence was generated, how assignment was concealed, or which people were masked.

Enrollment was 19. The registry lists the study status as terminated, with a start date of 2009-01 and primary completion in 2011-06. It does not report the reason for termination or explain whether termination affected recruitment, follow-up, or analysis. The phase is listed as NA. No protocol details should be inferred from those labels.

The primary endpoint is mean peak knee flexion during swing phase, measured by computerized gait analysis. Its stated time points are baseline, 1-month and 4-month post-injection. The study description also identifies peak knee velocity during preswing and initial swing, and gait function based on the 6-Minute Walk and temporal-distance measures. The registry lists two outcome measures and two analyses, but the posted record does not provide enough detail to map every analysis to a specific measure or comparison.

The registered research questions frame comparisons between the experimental and control groups. However, the registry record does not report the analytic model, the planned contrast at each time point, or whether the primary comparison was adjusted for baseline. It also does not state whether all randomized participants were included in the primary analysis. These omissions limit assessment of how closely the posted findings, if any, would correspond to the stated trial question.

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.

Before assignment: Strict inclusion criteria (e.g., walking velocity, rectus femoris spasticity, and target kinematic aspects of peak knee flexion in swing) eliminated many potential participants. 72 participants screened by phone, 30 declined/disqualified, 42 underwent clinical and gait analysis baseline screening, 23 disqualified. A total of 19 were enrolled

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 Mean Peak Knee Flexion During Swing Phase of Gait, measured over baseline, 1-month and 4-month post-injection.

Mean peak knee flexion during swing phase is a continuous gait measure expressed in degrees. Computerized gait analysis records knee motion during walking, and the endpoint is described as the average of peak knee flexion during the swing phase. The registry specifies assessment at baseline, 1-month and 4-month post-injection.

The endpoint is relevant to the stated condition because the registry describes stiff knee gait as reduced knee flexion during swing. Swing-phase knee movement is considered in relation to foot clearance and gait mechanics. This makes the measure a way to quantify a feature of the gait pattern rather than a direct measure of every aspect of walking function or safety.

The primary measure is a mean, so interpretation depends on the group values and on how variable individual measurements are. A difference in group means would describe an average contrast; it would not show that every participant changed in the same way. The standard deviation is the stated measure of dispersion, which describes variability among observations around the mean.

The registry record does not report the observed mean or standard deviation for either group at any time point, nor a between-group estimate or its uncertainty. Consequently, the direction, magnitude, and precision of any difference in peak knee flexion are not available in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, double-masked, and parallel. In general, randomization assigns participants to comparison groups using a chance-based process. Its purpose is to reduce systematic differences in prognosis between groups, although chance imbalances can remain, especially in a small study. The registry does not report the sequence-generation or allocation-concealment procedures, so those aspects of implementation cannot be evaluated.

What does masking contribute?

In general, masking means that specified people are kept unaware of assignment. This can reduce the influence of expectations on participant reporting, treatment decisions, outcome assessment, or analysis, depending on who is masked and how masking is maintained. The record labels the trial double-masked but does not say which roles were masked or whether masking was assessed. The label alone does not establish that masking was successful.

How should the continuous endpoint be understood?

Peak knee flexion is a continuous measurement reported as a mean, with standard deviation as the stated dispersion measure. A mean describes the central average in a group. A standard deviation describes how spread out individual observations are around that average; it is not the uncertainty in the mean or a confidence interval. Comparing means can summarize an average group contrast, but the estimate’s precision also depends on the amount of data and the variability. The posted record does not report the endpoint means or standard deviations, so neither the contrast nor its precision can be evaluated.

For a repeated assessment, an analysis could compare groups at a particular time point, compare changes from baseline, or model observations across time. These approaches answer related but not identical questions and can use different assumptions. This is general statistical context, not a description of the trial’s analysis. The registry record does not report which approach was used, how baseline measurements were handled, or whether the analysis accounted for within-person correlation across assessments.

What do statistical significance and confidence intervals address?

In general, a significance test evaluates how compatible the observed data are with a specified null hypothesis under the test’s assumptions. A p-value is not the probability that the null hypothesis is true, and it does not describe the size or practical relevance of an effect. A confidence interval gives an estimate together with a range reflecting statistical uncertainty under a method’s assumptions. It can help readers see both the estimated direction and the range of effect sizes compatible with the data. Neither a p-value nor a confidence interval is reported for the primary comparison in the registry record.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when outcome variability is greater than a statistical model assumes. If the model understates variability, standard errors can be too small and intervals too narrow, making results appear more precise than warranted. This issue is especially relevant to count outcomes and some categorical models; the primary endpoint in this trial is continuous. The record does not report an over-dispersion assessment, and it does not provide enough information to determine whether this concern applies to any secondary analysis.

How should the planning illustrations be read?

The stated planning framework uses a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes detectable effects as fractions of the observed effect. In general, a planning calculation estimates the sample size needed under its assumptions to target a chosen power for a specified effect. It is not a measure of the probability that the completed study found a true effect, and it is not observed power. The posted planning values and the observed effect estimate are not reported in the registry record, so the illustrations cannot be independently interpreted from the information available.

The registry record does not report the statistical analysis plan, the test or model used for the primary endpoint, covariate adjustment, handling of repeated measurements, or any interim analyses. These details matter because they define the estimand, assumptions, and uncertainty calculation. No particular method should be attributed to this trial without that information.

10. Multiplicity, Missing Data and Analysis Populations

The study description raises several outcome questions: mean peak knee flexion, peak knee velocity in two gait phases, and gait function based on the 6-Minute Walk and temporal-distance measures. The primary endpoint also has assessments at baseline, 1-month and 4-month post-injection. When multiple outcomes, time points, or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. General approaches to this issue include prespecifying a primary comparison, ordering tests, or adjusting for multiple testing. The registry record does not report a multiplicity strategy or specify a single primary time-point contrast.

Missing data can affect interpretation if participants with unavailable measurements differ from those whose data are observed. General analysis methods make different assumptions about why measurements are missing, and those assumptions can influence estimates. The registry record does not report how many participants contributed data at each assessment, whether any measurements were missing, why data might be absent, or how missing values were handled.

The record does not identify the primary analysis population or state whether analyses followed an intention-to-treat approach, a per-protocol approach, or another definition. It also does not report whether participants were analyzed according to randomized assignment or according to treatment received. These distinctions affect what population a treatment contrast represents. Enrollment of 19 alone does not establish the analysis denominator at any outcome or time point.

Without these details, readers cannot assess the protection against selective outcome reporting, the handling of incomplete follow-up, or the exact population represented by an estimate. These are unreported analysis features, not evidence that a particular procedure was or was not used.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse event counts for the botulinum toxin injection group and the saline injection group. In the botulinum toxin group, 0 participants with serious adverse events are recorded among 10 at risk. In the saline group, 0 participants with serious adverse events are recorded among 9 at risk. The corresponding other-adverse-event figures are 0 affected among 10 at risk and 0 affected among 9 at risk, respectively.

These entries describe what the registry reports for the listed groups; they do not establish that no adverse events occurred outside the recorded categories or reporting period. The record does not list top serious adverse event terms. Death information is not reported in the registry record: the death fields are not populated with a count. That should not be read as a reported zero.

Counts from a small enrolled sample provide limited information about uncommon events or about differences in event frequency. The record does not report detailed event definitions, observation duration for safety, or a fuller accounting of event timing and severity. These figures are descriptive safety data, not a comparison that by itself establishes the presence or absence of risk.

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

The record identifies a randomized comparison of botulinum toxin A injection to the rectus femoris with saline injection for stiff knee gait after acquired brain injury. It specifies mean peak knee flexion during swing as the primary endpoint and names the assessment schedule. It also describes questions about knee velocity and gait function. This establishes what the trial set out to investigate, not what the comparison found.

The posted results do not report numerical primary outcome findings. There is no reported group mean, standard deviation, treatment contrast, confidence interval, or p-value for the primary endpoint. The secondary gait questions likewise lack reported estimates. As a result, the available registry information does not show whether the groups differed, in which direction, by how much, or with what precision.

Even if an estimate were available, a group-average contrast would not mean that every participant had the same response. Statistical significance would not by itself establish clinical importance, and a non-significant finding would not establish equivalence. Equivalence or non-inferiority requires an appropriate design, margin, and analysis; those are not reported in the registry record.

The enrollment of 19 and the terminated status are important context, but neither explains the reasons for termination nor establishes how many participants completed follow-up. The missing analysis details also mean the treatment contrast and target population cannot be fully characterized. The serious adverse event entries record no affected participants in either listed group, but the available safety information is limited and death counts are not reported.

Accordingly, the registry record supports a description of the research question, design labels, measurement schedule, enrollment, and recorded adverse-event counts. It does not support a conclusion about the efficacy of either injection, the clinical importance of any gait change, or the comparative safety of the interventions.

13. Why This Trial Matters Statistically

This trial is statistically notable because it asks a focused question about a measurable feature of gait while also naming broader functional outcomes. A computerized measure of peak knee flexion can quantify a movement characteristic, whereas walking tests and temporal-distance measures address different aspects of function. Distinguishing these outcome types matters: a change in a movement measure would not automatically establish a change in walking capacity or everyday mobility.

The repeated schedule—baseline, 1-month and 4-month post-injection—also makes the definition of the treatment comparison important. A group contrast at a follow-up time, a change from baseline, and a pattern across time can each describe different estimands. The registry record does not report which contrast was primary, so the intended statistical interpretation cannot be fully reconstructed.

The enrollment of 19 and terminated status make transparent reporting of denominators, estimates, and uncertainty especially useful for judging how much information the trial contributes. The registry does not report those primary outcome results or the analysis population. Without them, readers cannot distinguish a precise estimate near no difference from a highly uncertain estimate that is compatible with a range of possibilities.

The record also illustrates why registry descriptions and outcome results serve different roles. The description states the clinical rationale and research questions; the posted outcome information would be needed to evaluate the measured comparison. Here, that numerical evidence is not reported in the registry record. The study’s design labels and registered questions therefore cannot stand in for outcome estimates or an analysis plan.

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 for statistical interpretation is the absence of numerical primary outcome results. Although mean peak knee flexion and its assessment times are described, the record gives no group values, dispersion estimates, treatment contrasts, confidence intervals, or test results. The direction and precision of the primary comparison are therefore unavailable.

Enrollment was 19, but the registry does not report the number analyzed at each assessment or the number with complete follow-up. Its terminated status is recorded without a reason. Without those details, readers cannot assess attrition, the impact of termination, or whether the analysis population differs from the enrolled group.

The registry identifies randomization, double masking, and a parallel design but does not describe sequence generation, allocation concealment, which roles were masked, or whether masking was maintained. It also does not report the analysis model, baseline handling, repeated-measures method, covariate adjustment, multiplicity procedure, or missing-data approach. These omissions prevent a detailed assessment of risk of bias and analytic assumptions.

The listed research questions encompass several gait outcomes and multiple assessment times, while a multiplicity strategy is not reported. The registry also does not provide detailed eligibility criteria, intervention dose, or a fuller safety observation description. The absence of these details should be treated as uncertainty about what was done or reported, not as evidence that a particular method was omitted in practice.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy of Botulinum Toxin Injections in the Rectus Femoris to Treat Stiff Knee Gait Following Acquired Brain Injury — NCT00900666.
• Registry record last updated 2013-06-24; status last verified 2013-05.
• Results first posted 2013-06-24.
• 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 randomized, double-masked, parallel trial comparing botulinum toxin A injection to the rectus femoris with saline injection for stiff knee gait following acquired brain injury. Enrollment was 19. The study is listed as terminated, with start date 2009-01 and primary completion in 2011-06.

The primary endpoint is mean peak knee flexion during swing phase, measured by computerized gait analysis at baseline, 1-month and 4-month post-injection. Other stated questions concern peak knee velocity and gait function. Numerical outcome results and the statistical analysis details are not reported in the registry record.

The record lists 0 serious adverse events among 10 at risk in the botulinum toxin group and 0 among 9 at risk in the saline group; other adverse events are also recorded as 0 affected in each group. Death counts are not reported. The available information describes the trial’s purpose and recorded safety counts but does not establish its outcome effects.