Safety and Efficacy of IM Injections of PLX-PAD for the Regeneration of Injured Gluteal Musculature After Total Hip Arthroplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of IM Injections of PLX-PAD for the Regeneration of Injured Gluteal Musculature After Total Hip Arthroplasty (NCT01525667), a randomized phase 1, phase 2 study. The primary outcome is Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength..

2. Clinical Question

The registry describes a Phase I/II randomized, double-blind, placebo-controlled study. The trial record reports an enrollment of 20 and lists three treatment arms. The primary endpoint concerns strength on the injured side over the interval from Day 0 to Week 26. The registry also lists secondary outcomes concerning muscle volume, mean fiber diameter, pelvic shift, and pain. The record does not provide enough detail to determine how the primary endpoint was selected relative to those other outcomes, or what clinical magnitude of change would be considered important.

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled, parallel-group Phase I/II study. Its official title specifies intramuscular injections of allogeneic PLX-PAD for regeneration of injured gluteal musculature after total hip arthroplasty. The stated brief summary describes a single-dose local administration, while the arm descriptions characterize each study arm as a single course of multiple intramuscular injections. The detailed dosing schedule is not reported in the registry record.

The trial has three listed arms: PLX-PAD Low Dose, PLX-PAD High Dose, and Placebo. The interventions are named 150M PLX-PAD, 300M PLX-PAD, and Placebo. The posted primary outcome summaries include 7 participants in the low-dose arm, 6 in the high-dose arm, and 7 in the placebo arm. These are the arm counts associated with the outcome summaries; the registry does not explain whether they represent all randomized participants or all participants with evaluable primary-outcome data.

The registry lists enrollment of 20, a start date of 2012-11, primary completion in 2013-12, and status as completed. The sponsor is Pluristem Ltd. No additional information about the randomization sequence, allocation concealment, recruitment, protocol deviations, or the duration of follow-up beyond the outcome timeframes is reported in the registry record.

The primary endpoint is change in injured-side maximal voluntary isometric contraction moment from Day 0 to Week 26, measured in Newtons. Four secondary outcomes are listed, including changes in muscle volume and visual analog scale pain score through Week 26. The record does not report the full set of methods for those outcomes in the information summarized for the primary comparison. In particular, the registry record does not specify how missing measurements, repeated observations, or multiple comparisons were handled.

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 Change From Day 0 to Week 26 in the Maximal Voluntary Isometric Contraction (MVIC) Moment of the Injured Side to Assess Gluteus Medius Strength., measured over Day 0 to Week 26.

The primary endpoint is change from Day 0 to Week 26 in the maximal voluntary isometric contraction (MVIC) moment of the injured side. The registry says it was measured by isometric dynamometry to assess gluteus medius force strength, with the unit reported as Newtons. MVIC is a measure of force generated during a voluntary contraction under a specified testing procedure. In this trial, the measurement focuses on the side identified as injured after total hip arthroplasty.

Using change over time makes the endpoint a comparison of the Week 26 measurement with the Day 0 measurement, rather than a Week 26 value alone. The registry labels the outcome as a least-squares mean and reports standard error as the dispersion measure for the arm-level summaries. It also reports mixed-model comparisons as differences between least-squares means. The posted arm summaries are 31.17 with a standard error of 6.97 for PLX-PAD Low Dose, 20.36 with a standard error of 7.61 for PLX-PAD High Dose, and 5.43 with a standard error of 6.46 for Placebo.

General: a strength endpoint can quantify a functional measurement, while a change score describes its movement over the specified follow-up interval. Statistical evidence about a group difference does not establish whether that difference is important to participants. A clinical threshold for meaningful change is not reported in the registry record, nor are details of measurement reliability or interpretation beyond the stated assessment purpose.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry names a mixed models analysis for both reported primary comparisons. It reports least-squares mean differences, confidence intervals, and p-values. The exact model specification is not reported in the registry record. For example, the record does not state which covariates were included, how repeated measurements were represented, what covariance structure was used, or how missing observations were handled. Those details matter because a mixed model’s estimates depend on its structure and assumptions.

What a least-squares mean represents

General: a least-squares mean is a model-based estimate of a group mean. It may account for features included in the statistical model, unlike a simple arithmetic mean calculated directly from individual observations. The registry labels the arm summaries as least-squares means and the comparisons as differences between least-squares means. Because the model details are not reported, the adjustments embodied in these estimates cannot be fully assessed from the registry record.

The arm-level values are 31.17 for PLX-PAD Low Dose, 20.36 for PLX-PAD High Dose, and 5.43 for Placebo. Their reported standard errors are 6.97, 7.61, and 6.46, respectively. A standard error describes the estimated sampling uncertainty of an estimate, rather than the spread of individual participants’ measurements. It can help indicate how precisely a group mean is estimated, but it does not describe the range of participant-level responses.

How to read confidence intervals

General: a confidence interval gives a range of values compatible with the data under the statistical model and its assumptions, at the stated confidence level. It expresses uncertainty around an estimate; it is not a range that contains a fixed proportion of individual outcomes. The registry reports 95% confidence intervals for the two comparisons. The low-dose versus placebo difference is 25.74, with an interval from 7.61 to 43.86. The high-dose versus placebo difference is 14.93, with an interval from -7.12 to 36.99. The first interval excludes zero; the second includes zero. This describes the intervals’ relation to a no-difference value, not the clinical importance of the estimates.

What the p-values can and cannot say

General: a p-value measures how unusual results at least as incompatible with a specified null model would be if that null model and the analysis assumptions held. It is not the probability that a treatment effect is real, and it does not quantify the size or importance of a difference. The registry reports p = 0.007 for the low-dose comparison and p = 0.18 for the high-dose comparison. The record does not state a prespecified significance threshold or whether these p-values were adjusted for multiple testing. As a result, the p-values should be interpreted alongside the estimates, confidence intervals, trial size, and the unreported analysis plan.

A mixed model can be used to analyze outcomes measured over time or data with grouping structure. General: such models can account for correlation among observations when the model is specified to represent that dependence. The fact that the registry names a mixed models analysis does not reveal how it was applied in this trial. It would be inappropriate to infer specific random effects, fixed effects, covariate adjustments, or assumptions not described in the record. The endpoint is a change from Day 0 to Week 26, but whether the model used only those two time points or additional measurements is not reported in the registry record.

Why sample size and uncertainty matter

The primary outcome summaries include 7 participants in the low-dose arm, 6 in the high-dose arm, and 7 in placebo. These are small analysis counts, and the confidence intervals are important for seeing how much uncertainty remains around the comparisons. A nonsignificant p-value does not establish equivalence or absence of an effect. In particular, the high-dose interval includes both negative and positive differences, so the result does not precisely determine the direction of a group difference.

General: planning calculations estimate the sample size that might be required under specified assumptions; they do not describe how much power a completed trial actually had. The planning assumptions associated with the page use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Any such values are planning illustrations, not observed trial outcomes or proof that the original trial was adequately powered. The registry’s own sample-size justification is not reported in the registry record.

Over-dispersion and model fit

General: over-dispersion occurs when observed variation is greater than a statistical model expects. If a model understates variability, uncertainty can appear too small and inferential results can be misleading. The primary outcome is continuous and the registry reports standard errors, but it does not report a model-fit assessment or evidence of over-dispersion. This is not a claim that over-dispersion occurred; it is a general reason to evaluate the model and its uncertainty assumptions when interpreting model-based results.

The posted results give the comparison estimates and their uncertainty but do not permit independent assessment of the full model. Individual participant data, the prespecified statistical analysis plan, and details of diagnostics are not reported in the registry record. Interpretation should therefore distinguish the reported model results from claims about the model’s unreported implementation.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("PLX-PAD Low Dose", "PLX-PAD High Dose", "Placebo")
n   <- c(7, 6, 7)
m   <- c(31.17, 20.36, 5.43)
sp  <- c(6.97, 7.61, 6.46)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  PLX-PAD Low Dose  7  31.170  18.441  14.115  48.225
CARM  PLX-PAD High Dose  6  20.360  18.641  0.798  39.922
CARM  Placebo  7  5.430  17.092  -10.377  21.237

11. Analyses Reported by the Sponsor

The primary comparisons reported by the sponsor are mixed models analyses of least-squares mean differences. For PLX-PAD Low Dose versus Placebo, the reported difference is 25.74, with a 95% confidence interval from 7.61 to 43.86 and p = 0.007. For PLX-PAD High Dose versus Placebo, the difference is 14.93, with a 95% confidence interval from -7.12 to 36.99 and p = 0.18. These are the sponsor’s reported analyses in the registry record.

The arm summaries show least-squares means and standard errors, while the reported comparisons come from a mixed models analysis. A simple calculation from arm summaries would not necessarily reproduce the sponsor’s adjusted or model-based comparison, particularly without individual data and the model specification. The sponsor’s analysis is therefore the primary inferential result to describe. The registry record does not report a discrepancy between that analysis and a recalculation.

The two sponsor-reported comparisons are against placebo; a direct low-dose versus high-dose comparison is not reported in the registry record. The reported difference and p-value also do not establish whether the magnitude is clinically important, because a threshold for meaningful change is not reported. The underlying model details and multiplicity handling are likewise not reported in the registry record, limiting independent assessment of how the sponsor’s estimates were obtained.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and four secondary outcomes. The secondary outcomes concern change in muscle volume from Day 0 to Week 26, mean fiber diameter from Day 1 to Week 12, the ratio of injured to contralateral pelvic shift from Day 0 to Week 26, and visual analog scale pain score from Day 0 to Week 26. There are also two reported comparisons for the primary endpoint, each comparing a PLX-PAD dose group with placebo.

When multiple outcomes, time points, treatment contrasts, or analyses are examined, the chance of obtaining at least one apparently unusual result can increase. General: multiplicity procedures can control or otherwise address this issue, but the method depends on which comparisons were planned and which claims are intended. The registry record does not report whether the two primary comparisons were treated as co-primary, whether a hierarchy was used, or whether p-values were adjusted for multiplicity. A prespecified analysis plan or protocol could clarify this, but it is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The posted outcome summaries include 7 participants in the low-dose arm, 6 in the high-dose arm, and 7 in placebo, while overall enrollment is 20. The record does not explain the relation between these counts, randomization, follow-up completion, and inclusion in the endpoint analysis. Reasons for missing measurements, imputation methods, sensitivity analyses, and assumptions about missingness are not reported.

The analysis population is not identified in the registry record. It is therefore unclear whether the primary analysis followed an intention-to-treat principle, included participants with available measurements, or used another defined population. The registry also does not report protocol deviations or a per-protocol analysis. These omissions limit assessment of potential bias from participant exclusions or missing outcomes.

Interim analyses, stopping rules, and any adjustments related to interim monitoring are not reported in the registry record. The original sample-size justification is also not reported. Without these details, the posted p-values and confidence intervals can be described as the reported results, but their place within the complete prespecified analysis strategy cannot be fully evaluated.

13. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: humeral head fracture (14.3%), periurethral cyst (14.3%).

The registry reports serious adverse events for the three arms. In the 150M PLX-PAD group, 1 of 7 participants was recorded as affected by a serious adverse event; in the 300M PLX-PAD group, 0 of 6 were affected; and in the Placebo group, 1 of 7 were affected. The registry lists other adverse events for 7 of 7 participants in the 150M group, 6 of 6 in the 300M group, and 7 of 7 in Placebo. These are the posted counts, not estimates of comparative risk.

The registry lists HUMERAL HEAD FRACTURE and PERIURETHRAL CYST among the top serious adverse event terms, each at 14.3%. It does not report enough information to assign each term to a particular treatment arm or describe its clinical course. Deaths are not reported in the registry record.

General: adverse-event counts in small groups are descriptive and do not, by themselves, establish whether an event was caused by an intervention. The record does not provide event-level timing, severity beyond the serious classification, relatedness assessments, or a detailed account of withdrawals due to adverse events. The small arm counts also limit how precisely uncommon events can be compared. These figures should be read as the safety information recorded in the registry, not as a complete safety profile or proof of comparative safety.

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

The primary endpoint captures change in measured gluteus medius strength on the injured side between Day 0 and Week 26. The registry reports a higher least-squares mean change in each PLX-PAD arm than in placebo, with a larger reported estimate for the low-dose versus placebo comparison than for the high-dose comparison. These summaries describe the posted trial results; they do not establish why the arm estimates differ.

For the low-dose comparison, the reported difference is 25.74, and its 95% confidence interval from 7.61 to 43.86 excludes zero. For the high-dose comparison, the estimate is 14.93, and its 95% confidence interval from -7.12 to 36.99 includes zero. The latter result is uncertain about the direction of the difference. A difference in whether confidence intervals include zero does not itself establish that the two dose groups differ from each other.

These results do not determine whether an observed change is clinically meaningful. The registry does not report a threshold for meaningful improvement, nor does the endpoint alone establish recovery of muscle function in everyday activities. The primary outcome is a measurement of force strength; broader outcomes would require interpretation of the other measures and their results. The record lists secondary outcomes but does not establish from the primary result whether pain, muscle volume, fiber diameter, or pelvic shift changed in a particular way.

The results also do not establish durability beyond the stated primary endpoint timeframe, effects in populations beyond those enrolled, or the balance of benefits and harms. The posted arm counts are small, and the registry does not report enough detail to assess missing-data assumptions, the analysis population, or the model specification fully. Safety counts are descriptive and cannot establish causation or rule out uncommon risks.

In general, a randomized, blinded comparison can help reduce some sources of bias, but the strength of conclusions still depends on conduct, complete follow-up, analysis choices, and precision. The registry record identifies the design as randomized and double-blind, but further details on implementation are not reported. The primary results should therefore be understood as estimates from this completed trial, with uncertainty and reporting limitations, rather than as definitive statements about clinical effect.

15. Why This Trial Matters Statistically

This trial illustrates the distinction between an arm-level outcome summary and a treatment comparison. The least-squares mean changes describe each arm, while the mixed models differences compare each PLX-PAD group with placebo. Those quantities answer related but different questions. Keeping them separate helps prevent an arm summary from being mistaken for an adjusted treatment effect.

It also shows why effect estimates and confidence intervals add information beyond p-values. The low-dose comparison has a reported estimate of 25.74 with an interval from 7.61 to 43.86, while the high-dose comparison has an estimate of 14.93 with an interval from -7.12 to 36.99. The intervals make visible both the direction of the estimates and the uncertainty around them. A p-value alone would not convey the range of differences compatible with the model.

The trial’s small outcome counts are especially relevant to precision. The primary summaries include 7 participants in the low-dose group, 6 in the high-dose group, and 7 in placebo. Small groups can leave considerable uncertainty, particularly when variation is present. The standard errors reported for the arm summaries help describe uncertainty in their estimated means, but do not communicate the range of individual outcomes.

Another statistical lesson is that comparing two treatment-versus-placebo p-values is not equivalent to testing whether the treatment groups differ from each other. The registry reports no direct dose comparison. Interpretation should not turn the different p-values into a claim of a dose-response pattern.

Finally, the listed secondary outcomes make transparency about multiplicity, missing data, and the analysis plan important. Those details are not reported in the registry record. Their absence does not negate the posted analyses, but it limits how fully their place within the overall study plan can be judged. The trial is therefore useful for illustrating both the value of model-based estimates and the importance of reporting enough methods to evaluate them.

16. 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 trial-specific limitations follow from the information in the registry record. The primary outcome summaries include 7 participants in the 150M PLX-PAD arm, 6 in the 300M PLX-PAD arm, and 7 in placebo. The record lists enrollment of 20 but does not explain whether every enrolled participant was randomized, completed follow-up, or contributed to the primary analysis. The relation between enrollment and analyzed counts is not reported.

The exact mixed-model specification is not reported in the registry record. Covariate adjustment, repeated-measures structure, covariance assumptions, model diagnostics, and handling of missing measurements are not described. Without those details or individual participant data, the sponsor’s estimates cannot be independently reconstructed from the registry summary.

The record does not report the sample-size justification, target effect, or any planned precision criterion. The planning assumptions associated with sample-size illustrations are not a substitute for the trial’s original design rationale. Interim analyses, stopping rules, and any adaptations are not reported in the registry record.

Although four secondary outcomes are listed, multiplicity procedures and the intended hierarchy among outcomes and comparisons are not reported. This makes it difficult to assess how the primary p-values fit within all planned statistical testing. The clinical threshold for meaningful change in MVIC moment is also not reported, so statistical evidence cannot be translated into clinical importance from the record alone.

Other details that could aid interpretation—including fuller eligibility criteria, randomization implementation, allocation concealment, protocol deviations, analysis populations, outcome measurement reliability, and reasons for missing data—are not reported in the registry record. The adverse-event summary provides counts and selected serious-event terms but not event-level timing, relatedness, or outcomes. These limitations restrict both independent evaluation of the analyses and the conclusions that can be drawn about generalizability and safety.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Safety and Efficacy of IM Injections of PLX-PAD for the Regeneration of Injured Gluteal Musculature After Total Hip Arthroplasty — NCT01525667.
• Registry record last updated 2015-09-21; status last verified 2015-01.
• Results first posted 2015-02-23.
• 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.

20. Record Summary

NCT01525667 is a completed Phase I/II randomized, double-blind, placebo-controlled parallel-group trial sponsored by Pluristem Ltd. The registry lists enrollment of 20 and evaluates intramuscular PLX-PAD after total hip arthroplasty in participants with injured gluteal musculature. The three arms are PLX-PAD Low Dose, PLX-PAD High Dose, and Placebo.

The primary endpoint is change from Day 0 to Week 26 in injured-side MVIC moment, measured in Newtons. The registry reports two mixed models comparisons against placebo. The low-dose comparison has a least-squares mean difference of 25.74, a 95% confidence interval from 7.61 to 43.86, and p = 0.007. The high-dose comparison has a difference of 14.93, a 95% confidence interval from -7.12 to 36.99, and p = 0.18.

Four secondary outcomes are listed. The registry does not report the full model specification, missing-data methods, analysis population, multiplicity procedure, or original sample-size justification. The results should be interpreted with those reporting limits and the small posted primary-outcome arm counts in mind.