Emervel® Deep Lidocaine vs. Juvederm® Ultra Plus in Treatment of Moderate to Severe Facial Wrinkles and Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Emervel® Deep Lidocaine vs. Juvederm® Ultra Plus in Treatment of Moderate to Severe Facial Wrinkles and Folds (NCT01205061), a randomized na study. The primary outcome is Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, evaluator-blinded, active-controlled, multicenter study comparing Emervel Deep Lidocaine with Juvederm Ultra Plus. Its official title calls it a split-face comparison, and the treatment descriptions specify injection into NLFs on each treatment side. The registry also categorizes the model as parallel. Those descriptions differ; the record does not explain the categorization. The split-face description means the comparison is based on treatment sides within participants, rather than simply on two separate groups of participants.

The registry reports enrollment of 162 participants and lists both treatment arms with 162 participants. For the primary endpoint, the stated ITT population included participants who were randomized and received an injection on both treatment sides. The record does not give further details about how many participants had measurements available at each assessment or how missing measurements were handled.

The primary endpoint was mean change from baseline in WSRS at Week 24 after the final initial injection. For participants without a touch-up injection, the assessment was at Week 24; for participants with a touch-up injection at Week 3, it was at Week 27. The record also lists assessments at other time points, participant pain assessments, self-assessment of wrinkle severity, and adverse events.

The study is marked completed. Its phase is listed as not applicable. The protocol’s sample-size justification, any interim analyses, and the full statistical analysis plan are not reported in the registry record. The registry record does not identify the number of centers or provide further operational details about randomization or evaluator blinding.

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: A total of 184 participants were screened, of which 162 participants received treatment in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) population included participants who were randomized and received an injection on both treatment sides.

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: The intent-to-treat population included all participants who were randomized and received an injection on both treatment sides.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection, measured over Baseline, Week 24 after final initial injection (Week 24 for participants without touch-up injection, Week 27 for participants with touch-up injection at Week 3).

The primary endpoint was mean change from baseline in the Wrinkle Severity Rating Scale (WSRS) at the primary assessment time. WSRS is described as a validated five-point reference scale, accompanied by photographs, for classifying the severity of deep facial wrinkles, specifically nasolabial folds. Its grades range from absent folds to extreme folds, and the registry describes the grades in terms of appearance and fold depth.

The endpoint uses change from baseline rather than the assessment score alone. A negative change indicates improvement in the recorded score. A mean summarizes the average change across the stated population, while the standard deviation describes the spread of individual changes around that mean. These two summaries answer different questions: the mean describes the group’s average change, and the standard deviation describes how variable participants’ changes were.

The primary assessment was Week 24 after the final initial injection, with the timing adjusted to Week 27 for participants who received a touch-up injection at Week 3. That timing distinction matters when interpreting the endpoint: the nominal assessment week was not identical for all participants under the registry’s definition. The record does not report a separate interpretation threshold for a clinically meaningful difference between treatments.

7. Results Posted in the Registry

• Juvederm Ultra Plus: mean -1.10 versus -1.10 on control; difference 0.00 (95% CI -0.16 to 0.16), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 3 After Final Initial Injection

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Juvederm Ultra Plus: mean -1.60 versus -1.60 on control; difference 0.00 (95% CI -0.14 to 0.14), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Juvederm Ultra Plus and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 12 After Final Initial Injection

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Juvederm Ultra Plus: mean -1.30 versus -1.30 on control; difference 0.00 (95% CI -0.16 to 0.16), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Juvederm Ultra Plus and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 36 After Final Initial Injection

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Juvederm Ultra Plus: mean -1.10 versus -1.10 on control; difference 0.00 (95% CI -0.15 to 0.15), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Juvederm Ultra Plus and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary WSRS summaries show the same mean change for both treatments at each of the reported secondary assessment times. The direction of change from baseline is negative at the reported time points, and the recalculated treatment contrasts are centered at zero. Taken together, this is a consistent pattern of matching arm-level means across the posted secondary WSRS assessments. It aligns with the primary result’s equal means, rather than presenting a secondary time point with a different direction in the posted averages.

This overall pattern does not by itself establish that treatment effects are identical at every time point. The summaries are rounded, and they do not provide participant-level paired differences or the analysis details needed to assess the precision of each contrast under the split-face design. The secondary outcomes also include participant self-assessment, pain assessments, and adverse events, but the registry record does not provide a complete set of posted numerical results for every listed outcome in the registry record.

General: Secondary outcomes can help describe whether the primary pattern is consistent across measurements and assessment times. However, when many outcomes or time points are examined, the chance of at least one apparently unusual result can increase. A multiplicity strategy can address that issue by adjusting interpretation or testing procedures. The multiplicity plan is not reported in the registry record, and no reported analyses are listed. For that reason, secondary findings without a reported adjustment should be read as supportive descriptions, not as independent confirmation of the primary comparison.

The secondary pattern is compatible with the primary arm-level result, but it does not resolve the limitations of the primary recalculation. In particular, it cannot supply the missing paired-analysis details, a clinically meaningful difference threshold, or a missing-data strategy. The registry’s posted summaries are informative about the reported means, while the strength of conclusions across multiple outcomes remains limited by the unreported analysis plan.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 3 After Final Initial Injection
• Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 12 After Final Initial Injection
• Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 36 After Final Initial Injection
• Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 48 After Final Initial Injection
• Mean Change From Baseline in Participant Self-Assessment of Wrinkle Severity at Week 24 After Final Initial Injection
• Participant Pain Assessment After the Initial Injection
• Participant Pain Assessment After the Initial Touch-up Injection
• Number of Participants With Adverse Event (AEs)

9. Statistical Interpretation

10. Statistical Methods Explained

General: A mean change is the average of participants’ change scores from baseline to the specified assessment. Negative values indicate a lower WSRS score than at baseline because the registry defines negative change as improvement. A group mean is not a description of every participant: individuals can have changes above or below the average. The standard deviation gives a measure of the spread of those changes, rather than the precision of the mean or the uncertainty in the treatment contrast.

For the primary endpoint, the posted mean change was -1.1 in each treatment arm. The corresponding standard deviations were 0.75 for Emervel Deep Lidocaine and 0.68 for Juvederm Ultra Plus. These summaries describe the observed arm-level changes. They do not, on their own, provide the paired within-participant distribution expected to be especially relevant to a split-face comparison.

What does a treatment contrast represent?

General: A treatment contrast expresses the difference between the outcome summaries for the two treatments. A contrast of 0.0 means the calculated difference between the posted means is zero at the precision shown. The recalculated primary contrast is 0.0 because the two posted means are both -1.1. This does not mean that every participant’s two sides changed identically; the arm means can be equal even when individual paired differences vary.

The registry record identifies the study as randomized and split-face, while the recalculated comparison is based on arm-level summary statistics. In a split-face study, each participant contributes observations under both treatments. A paired analysis uses the relationship between those two observations, which can affect the standard error and confidence interval. The within-participant correlation and details of any paired analysis are not reported in the registry record. As a result, the unadjusted recalculation should not be mistaken for a reported sponsor analysis or a full reconstruction of the intended split-face analysis.

What do the confidence interval and p-value add?

General: A confidence interval gives a range of values compatible with the data under the assumptions of the calculation. It conveys uncertainty about the estimated contrast; it is not a range containing a specified proportion of individual participant outcomes. The recalculated interval for the primary mean difference runs from -0.156 to 0.156. It includes zero, the value corresponding to no difference in the calculated mean contrast. The interval’s interpretation depends on the calculation’s assumptions, including the way the study design is represented.

General: A p-value measures how unusual the observed result, or a more extreme result, would be under a specified null hypothesis and statistical model. It does not give the probability that the null hypothesis is true, nor does it measure clinical importance. The unadjusted recalculated p-value is 1.0. Because the contrast is calculated from equal posted means, that value describes the result under the recalculation; it does not establish equivalence, prove that there is no difference, or replace a prespecified analysis.

Why can over-dispersion matter?

General: Over-dispersion occurs when the observed variability is greater than a statistical model assumes. If a model understates variability, standard errors can be too small and confidence intervals too narrow, making results appear more precise than the data justify. The primary endpoint is continuous, and its posted summaries include standard deviations. The registry record does not report an over-dispersion assessment or a model-based adjustment for it. The concept is relevant generally, but the record does not establish that over-dispersion occurred in this study.

What can be said about the analysis plan?

The registry record lists no reported analyses. It does not report the protocol’s sample-size justification, a prespecified treatment-difference margin, interim analyses, multiplicity adjustment, or the full statistical analysis plan. The posted means, standard deviations, and recalculated contrast can be described, but they do not reveal how the sponsor planned to handle the split-face structure or other analysis decisions. Where the sponsor’s own analysis is available, it would take precedence over a simple unadjusted recalculation; the registry record does not post such an analysis.

11. Confidence Intervals and Precision

The primary comparison has a recalculated mean difference of 0.0. Its confidence interval extends from -0.156 to 0.156. This interval includes zero and gives a range of contrasts compatible with the unadjusted calculation. It does not show that the true difference is exactly zero. Nor does it represent the range of individual participants’ responses.

General: Precision concerns how narrowly an estimate is determined by the data and the analysis assumptions. A narrower confidence interval indicates less uncertainty under those assumptions; a wider one indicates more. Precision and statistical significance are not measures of clinical importance. To judge whether the range excludes differences that matter clinically, a prespecified threshold is needed. A threshold for a meaningful between-treatment difference is not reported in the registry record.

The interval should be interpreted with particular care because the registry describes a split-face comparison, while the recalculation uses posted arm-level summary statistics. A paired analysis can depend on the correlation between the two sides within each participant. That correlation and the sponsor’s analysis are not reported in the registry record. The recalculated interval therefore summarizes the available means and standard deviations under its calculation, but may not represent the precision of a paired analysis.

The same mean change is reported for both treatments, and the recalculated interval is centered on zero. The interval nevertheless permits contrasts on either side of zero under the calculation. The record does not report a noninferiority or equivalence margin that would let readers determine whether the interval lies within an acceptable range. The posted estimate is consequently best read as a near-zero arm-mean contrast at the reported precision, with inferential limits shaped by the unreported analysis details.

12. Multiplicity, Missing Data and Analysis Populations

The registry record identifies the primary WSRS outcome and lists several secondary outcomes and assessment times. It does not report whether the statistical plan controlled for multiple testing, how outcomes were prioritized beyond the primary designation, or whether any adjustment was applied to secondary analyses. The record lists no reported analyses. Therefore, the extent to which multiplicity was addressed cannot be determined from the registry record.

General: Multiplicity arises when multiple outcomes, time points, or comparisons are examined. Without an appropriate plan, a collection of tests can produce apparently noteworthy results by chance more often than a single test. This is why secondary results are generally interpreted with more caution when the adjustment strategy is unknown. The posted summaries can describe patterns, but the registry record does not establish confirmatory status for individual secondary results.

The primary endpoint population is described as ITT and includes participants who were randomized and received an injection on both treatment sides. The record lists 162 participants in each treatment arm, but does not state how many had complete primary endpoint data, whether the ITT population was modified for a particular analysis, or how missing observations were handled. Missing-data assumptions, imputation methods, and sensitivity analyses are not reported in the registry record. Without those details, the effect of missing outcome data on the estimates cannot be assessed.

The registry describes a randomized evaluator-blinded split-face study, but does not report the full statistical analysis plan or the method used to account for the paired observations. It also does not report interim analyses or the sample-size justification. These omissions limit assessment of whether the posted summaries reflect the prespecified analysis, how uncertainty was handled, and whether analysis choices were made before or after results were known. They do not change the numerical summaries, but they constrain the conclusions that can be drawn from them.

13. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: colon cancer (0.6%), lung cancer metastatic (0.6%), uterine leiomyoma (0.6%), herpes zoster (0.6%), diarrhoea infections (0.6%).

The registry lists 7 participants with serious adverse events in each treatment group, 16 with other adverse events in each group, and 0 deaths in each group. Because the study is described as split-face, participants could have received both treatments on different sides. These group entries should not automatically be read as counts of independent participant groups or as proof that an event was caused by one treatment side. The registry record does not provide further attribution details in the registry record.

The listed serious adverse event terms include Colon cancer, Lung cancer metastatic, Uterine Leiomyoma, Herpes Zoster, Diarrhoea infections, and Small intestinal obstruction; each is displayed as 0.6%. These figures describe reported event categories in the registry and do not, by themselves, establish a causal relationship to either treatment. The record does not provide enough detail to determine the timing, duration, severity beyond the serious classification, or treatment attribution for each event.

General: Safety counts require attention to the population at risk, the definition of an event, and how events are attributed when participants receive both treatments. Equal counts in the posted groups do not prove equal risks, and counts alone do not establish a treatment effect on safety. The figures should be read as descriptive registry reporting, not as medical advice or a causal comparison.

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

The posted primary summaries show a mean WSRS change of -1.1 for each treatment at the designated assessment time. The recalculated unadjusted difference between those means is 0.0, and the corresponding interval includes zero. The main statistical description is therefore that the reported arm-level averages are the same at the precision shown, with an unadjusted recalculation centered on no difference.

That result does not demonstrate that the treatments are equivalent. Equivalence and noninferiority are specific statistical questions that require a prespecified margin and an analysis designed to address it. Neither a margin nor a reported sponsor analysis is present in the registry record. A p-value of 1.0 from the recalculation is not proof that no difference exists, and it does not establish that any possible difference is too small to matter.

The result also does not imply that every participant experienced the same change on both sides. The standard deviations show variation in individual changes, while the arm means describe only averages. The registry record does not provide the paired participant-level differences or within-participant correlation needed to characterize how often one side changed more than the other.

The confidence interval communicates uncertainty under the recalculation, but its relevance to the intended split-face comparison depends on the analysis assumptions. The registry does not report the paired analysis method, missing-data handling, or a clinically meaningful difference threshold. Consequently, the summaries support a narrow descriptive statement about posted means, not a definitive conclusion about equivalence, individual response, or clinical importance. They also should not be interpreted as medical advice or as a recommendation about treatment choice.

15. Why This Trial Matters Statistically

This trial is statistically notable because its registry description is a randomized split-face comparison. In that design, both treatments are evaluated within the same participant, which can make the participant the natural unit of comparison. The paired structure can account for participant characteristics shared by both sides, but appropriate precision depends on the relationship between the two sides’ outcomes. The registry record does not report the paired analysis details or within-participant correlation.

The posted arm means are identical at the reported precision, and the simple recalculated contrast is 0.0. That gives a clear example of why a point estimate alone is not the whole statistical result. The confidence interval adds uncertainty, while the missing paired-analysis details limit how directly that interval can be applied to the study’s design. Readers need to distinguish the descriptive equality of the posted averages from a formal equivalence conclusion.

The record also illustrates the importance of separating observed summaries from a planned statistical test. A registry can report means and standard deviations without reporting a complete analysis plan, missing-data procedures, multiplicity strategy, or clinically meaningful margin. Those pieces determine how a treatment contrast should be tested and how strong a conclusion it supports. Their absence does not invalidate the posted values, but it restricts what can be inferred from them.

Finally, multiple follow-up assessments can help describe the consistency of the outcome pattern over time, but they also raise questions about multiplicity and confirmation. The secondary WSRS means follow the same arm-level pattern as the primary result. Without a reported multiplicity plan and analysis details, that consistency is descriptive rather than a substitute for a prespecified inferential analysis.

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.

The most important trial-specific limitation for interpreting the primary contrast is the difference between the registry’s split-face description and the arm-level summary-statistic recalculation. A paired comparison relies on information about how each participant’s two side-specific outcomes relate. That information is not reported in the registry record, so the recalculated confidence interval may not reflect the precision of the intended paired analysis.

The registry lists 162 participants in each treatment arm and defines the primary ITT population as participants who were randomized and received an injection on both treatment sides. It does not report the number with observed primary outcomes, the amount or pattern of missing data, or how missing values were handled. The extent to which incomplete measurements could affect the primary or secondary results therefore cannot be assessed.

The record does not provide the sponsor’s statistical analysis, full statistical analysis plan, sample-size justification, interim-analysis information, or multiplicity approach. It also does not report a threshold for a clinically meaningful between-treatment difference. These omissions prevent assessment of the planned precision, the intended handling of multiple outcomes, and whether the observed interval excludes differences considered important for this study.

The registry categorizes the model as parallel while the official title describes a split-face comparison. The record does not explain this difference. Its posted adverse-event counts likewise do not provide detailed attribution to treatment side, which is relevant when participants received both treatments. These limitations concern interpretation of the registry information; they do not alter the reported means or event counts.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Emervel® Deep Lidocaine vs. Juvederm® Ultra Plus in Treatment of Moderate to Severe Facial Wrinkles and Folds — NCT01205061.
• Registry record last updated 2023-10-23; status last verified 2023-07.
• Results first posted 2023-10-23.
• 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

The registry record describes a completed, randomized, evaluator-blinded, active-controlled comparison of Emervel Deep Lidocaine and Juvederm Ultra Plus for moderate to severe facial wrinkles and folds. It reports enrollment of 162 participants and identifies the primary outcome as mean change from baseline in WSRS at the primary assessment time. The study is described as split-face, although the registry also categorizes its model as parallel.

At the primary assessment, both treatments had a posted mean change of -1.1. The recalculated unadjusted mean difference is 0.0, with a confidence interval from -0.156 to 0.156 and an unadjusted p-value of 1.0. The record lists 7 participants with serious adverse events and 16 with other adverse events in each group, with 0 deaths in each group.

The registry record does not report the sponsor’s analysis, missing-data methods, multiplicity strategy, sample-size justification, or clinically meaningful difference threshold. The posted summaries support description of the reported averages, but do not establish equivalence or resolve the uncertainty associated with the unreported paired-analysis details.