Treatment Of Dupuytren's Contracture With Collagenase Clostridium Histolyticum Injection (Xiapex): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment Of Dupuytren's Contracture With Collagenase Clostridium Histolyticum Injection (Xiapex) (NCT01229436), a non-randomized phase 3 study. The primary outcome is Total Passive Extension Deficit (TPED) at Baseline for First Injection.

2. Clinical Question

3. Trial Design

This was a prospective, open-label, single-group Phase 3 study of Xiapex injection for Dupuytren's contracture. The registry record lists non-randomized allocation and no masking. Enrollment was 254. The study is marked completed, with a start date of 2010-12 and primary completion in 2012-10. Pfizer is listed as the sponsor.

A single-group design follows participants receiving the intervention without a separate control arm. It can describe outcomes observed over time among enrolled participants, but by itself it cannot separate changes associated with treatment from changes that might occur for other reasons. Open-label status means the record does not describe masking of participants or study personnel. Whether assessors were masked is not reported in the registry record.

The registry summary describes assessment of finger range of motion, patient and physician ratings of treatment satisfaction and disease severity, recovery to normal activities, recovery time, pain medication use and healthcare resource utilization. The recovery information was to be assessed via a participant diary. The listed outcome measures also include passive extension deficit and range of motion for metacarpophalangeal and proximal interphalangeal joints, along with medication-use outcomes. The number of outcome measures is 35.

The primary outcome is named as baseline total passive extension deficit for the first injection. The registry record also lists follow-up measurements of total passive extension deficit and joint-specific passive extension deficit at specified time points after injections, as well as assessments after the last injection. Numerical results for these efficacy outcomes and details of the analysis plan are not reported in the registry record. The record lists zero analyses.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set(FAS):participants who received at least (\>=)1 injection of Xiapex,had \>=1 post-injection efficacy assessment(goniometric/participant-reported). 'N'(number of participants analyzed) includes total number of participants in FAS, however actual 'N' for this outcome is unknown as these data were not calculated as per planned analysis.

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 Total Passive Extension Deficit (TPED) at Baseline for First Injection, measured over Baseline for first injection.

The named primary outcome is total passive extension deficit, or TPED, at baseline for the first injection. It is measured in degrees and reported using a median and full range. TPED is defined as the sum of passive extension deficits in the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints. Finger goniometry is used to measure joint angles.

Passive extension is the angle reached when a finger is passively extended as far as possible toward normal extension. The passive extension deficit is the angle between that position and normal extension. In general, measuring joint angles gives a standardized way to describe movement limitation; the measure is relevant to the study's focus on finger motion. The baseline value for the first injection is the TPED measurement closest to, and before, that injection.

A baseline measure describes participants' status before the first injection; it is not itself a measure of change after treatment. The record names change from baseline in TPED and joint-specific deficit among secondary outcomes, with assessments at several follow-up times. The primary outcome description also says that the baseline after the first injection was used as the follow-up baseline for assessments after the last injection. The registry record does not report a numerical primary-outcome value or an efficacy estimate based on it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record names the primary outcome and its summary format, but detailed statistical methods are not reported in the registry record. The following explanations are general and clarify how the named measures and design features are commonly interpreted; they do not describe unreported analyses from this study.

What does a median and full range describe?

General: The median is the middle value when observations are ordered. It is less sensitive than the mean to unusually high or low observations, which can be useful when measurements are skewed. The full range gives the lowest and highest observed values and therefore describes the spread from one extreme to the other. A range does not show how observations are distributed between those extremes, and it is sensitive to extreme observations. The registry record names these summaries for baseline TPED but does not report the actual median or range.

What does the goniometric measure represent?

The record defines TPED as a sum of deficits measured at the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints. General: a summed score combines information from multiple component measurements into one measure. This can give a compact description of overall extension deficit across specified joints, while concealing differences among individual joints. The registry record separately lists joint-specific outcomes, which address those components individually. Measurement reliability, assessor training and procedures for resolving measurement disagreements are not reported in the registry record.

How should follow-up measurements be understood?

The listed secondary outcomes include changes from baseline at several time points after injections and after the last injection. General: repeated measurements can describe the course of an outcome over time. Measurements from the same participant are related, so analyses that treat them as independent observations may misrepresent uncertainty. Statistical methods for handling within-participant correlation, the precise analysis windows, and the handling of multiple injections are not reported in the registry record. The listed time points describe planned outcome timing; they do not establish that every participant contributed a measurement at every time point.

What does a confidence interval mean?

General: a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used to calculate it. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. Its interpretation depends on the analysis population, outcome definition, model and handling of missing observations. Numerical confidence intervals for efficacy outcomes are not reported in the registry record, so their precision cannot be assessed from this record.

Why does the single-group design matter?

General: a single-group study can describe outcomes among participants who receive an intervention, including changes between baseline and later assessments. A separate comparator group can help distinguish changes over time from changes that might have occurred without the intervention. Here, the record specifies a single-group model and no randomized comparator. The registry record does not report an adjustment strategy that would create a comparative estimate. Results from any within-group change would need to be interpreted as change in the observed group, not as a randomized treatment contrast.

What do planning illustrations represent?

General: sample-size calculations describe how many participants a hypothetical design might require under stated assumptions. They are planning illustrations, not evidence that a study achieved a particular probability of detecting an effect. The planning assumptions described for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect defined as a stated fraction of the observed effect. Those assumptions do not match this trial's single-group structure. The registry record does not report the trial's own sample-size justification, so the illustrations should not be read as its original design basis or as observed power.

General: over-dispersion occurs when observed variability is greater than a model assumes. If it is present and ignored, standard errors can be too small and uncertainty can appear lower than it is. The registry record does not identify a model for count outcomes or report whether over-dispersion was assessed. Likewise, the statistical model, covariate adjustment, significance tests and confidence-interval methods used for efficacy outcomes are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 35 outcome measures, spanning several related but distinct measures and assessment times. When many outcomes or time points are examined, the chance of finding an apparently notable result by chance can increase. General: multiplicity procedures can control or otherwise address that issue, but their choice depends on the analysis objectives and outcome hierarchy. Any multiplicity strategy, prespecified hierarchy or distinction between confirmatory and exploratory analyses is not reported in the registry record.

The record lists zero analyses. It does not provide numerical efficacy results, analysis-specific sample sizes, or a description of how missing measurements were handled. Missing-data methods are not reported in the registry record. In general, missing observations can affect estimates if participants with observed measurements differ systematically from those without them. The amount and pattern of missing efficacy data cannot be assessed from the record.

The described full analysis set includes participants who received at least one Xiapex injection and had at least one post-injection efficacy assessment. The outcome description says the participant count in the set includes all participants in that set, while the actual number analyzed for the outcome is unknown. This distinction matters: the size of the named analysis population does not establish how many observations contributed to a particular outcome or time point. The record does not report further analysis-population definitions, exclusions, or sensitivity analyses.

The study summary mentions participant diaries for recovery and resource-use information, but completion requirements and methods for incomplete diary entries are not reported in the registry record. It is therefore not possible to assess the completeness of those measurements or how any missing entries may have affected results.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: back pain (0.4%), pain in extremity (0.4%), rotator cuff syndrome (0.4%), dyspnoea (0.4%), epistaxis (0.4%).

The registry record lists 254 participants at risk for both serious and other adverse events in the Xiapex group. It reports 12 participants affected by serious adverse events and 212 affected by other adverse events. These are participant counts, not a measure of treatment effect relative to a control group. No separate control group is described in this single-group study.

The listed serious-event terms are back pain, pain in extremity, rotator cuff syndrome, dyspnoea, epistaxis and pneumothorax. Each term is recorded with a frequency of 0.4%. The record does not establish from these entries whether the events were caused by Xiapex, nor does it report details such as timing, duration, outcome or participant-level overlap among event categories. The death count is not reported in the registry record.

General: adverse-event summaries depend on how events were defined, collected and classified, and on the period of observation. Counts alone do not indicate comparative risk or causality. The registry record does not report a comparator group or an exposure-adjusted safety analysis. These figures should therefore be read as recorded safety counts within the study group, rather than as a comparison with another treatment or a conclusion about causation.

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

The record establishes that a prospective, open-label, single-group Phase 3 study was conducted in participants with Dupuytren's contracture who received Xiapex injection. It describes a primary baseline measure of total passive extension deficit and lists outcomes intended to capture joint movement, satisfaction, disease severity, recovery, pain medication use and healthcare resource utilization. It also reports participant counts for serious and other adverse events.

Those descriptions do not amount to a numerical account of efficacy. The registry record does not report the baseline TPED value, change from baseline, effect estimates, confidence intervals or efficacy-analysis results. It therefore does not show how much measured motion changed, how precise any change estimate was, or how participant and physician ratings related to motion. The listed outcomes should not be mistaken for reported findings.

The design also limits what can be inferred from any within-group changes. General: changes observed over time in a single group may reflect more than the intervention alone. Without a concurrent randomized comparator, the record cannot provide a randomized estimate of the difference between receiving and not receiving Xiapex. The absence of masking is another design feature to consider when interpreting assessments, particularly subjective ratings; whether or how it affected results is not reported in the registry record.

The adverse-event counts are descriptive. They do not establish that the intervention caused an event or quantify risk relative to another option. The record does not report a death count. Taken together, the record identifies the study's scope and the types of outcomes collected, but the efficacy information is insufficient to support a conclusion about the magnitude, precision or comparative meaning of treatment-related changes.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and outcome definitions shape interpretation. Its single-group, non-randomized, open-label structure means its stated aim of evaluating motion and patient- and physician-reported outcomes is not equivalent to a randomized comparison. Readers need to distinguish a description of outcomes over time from an estimate of what would differ under an alternative intervention or no intervention.

The primary outcome definition also matters. TPED is a sum across specified finger joints, measured with goniometry, and the named primary endpoint is a baseline value. A baseline description can characterize the study group, but it does not quantify post-injection change. The registry record lists change measures as secondary outcomes, yet their numerical analyses are not reported in the registry record. That distinction prevents a baseline endpoint name from being mistaken for an efficacy result.

The record lists 35 outcome measures, including repeated assessments and multiple domains. In general, a broad outcome set raises questions about analysis selection, missingness and multiplicity. These are important because readers need to know which outcomes were analyzed and how uncertainty was handled. The registry record lists zero analyses and does not report these methodological details.

Finally, the adverse-event counts illustrate why descriptive safety reporting is not the same as causal or comparative evidence. Without a comparator, the listed counts cannot quantify a difference between groups. The statistical value of the record is therefore chiefly in defining the design, outcome framework and limits of the reported information, rather than in supporting a numerical efficacy conclusion.

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 principal limitation of the registry record for statistical interpretation is the absence of numerical efficacy results. The primary outcome is defined as baseline TPED, but its median and full range are not reported. Numerical changes, estimates of uncertainty and analysis-specific participant counts are also not reported in the registry record.

The study has a single group, non-randomized allocation and no masking. No like-for-like control comparison is described. As a result, the record does not support a randomized comparison, and any change over time would not by itself isolate the effect of the intervention. The registry record does not describe assessor masking or methods intended to address confounding.

The record describes a full analysis set requiring at least one injection and at least one post-injection efficacy assessment, but says the actual number analyzed for the primary outcome is unknown. Outcome-specific missingness, exclusions, adherence, and methods for handling incomplete follow-up are not reported in the registry record. These omissions make it difficult to determine how representative the analyzed observations were of all enrolled participants.

The registry record lists 35 outcome measures and zero analyses. Statistical methods for repeated measurements, multiplicity, model selection, covariate adjustment and uncertainty estimation are not reported in the registry record. The study summary mentions diary-based recovery assessment and other resource-use measures, but the analysis of those data is not reported. The sample-size justification for the trial is not reported in the registry record; planning illustrations based on two-arm assumptions should not be confused with the study's own design rationale.

Safety reporting is also limited to the listed counts and serious-event terms. The record does not report a death count, causal attribution details or comparative safety results. These limitations restrict both efficacy and safety interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment Of Dupuytren's Contracture With Collagenase Clostridium Histolyticum Injection (Xiapex) — NCT01229436.
• Registry record last updated 2014-03-17; status last verified 2014-01.
• Results first posted 2014-03-17.
• 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

NCT01229436 is a completed, prospective, open-label, non-randomized, single-group Phase 3 study of Xiapex injection for Dupuytren's contracture, sponsored by Pfizer. Enrollment was 254, and the registry record lists dates from 2010-12 to primary completion in 2012-10.

The primary outcome is baseline total passive extension deficit for the first injection, measured in degrees and summarized by median and full range. The record lists 35 outcome measures and zero analyses. Numerical efficacy results and detailed statistical methods are not reported in the registry record.

The safety entries list 12 participants with serious adverse events and 212 with other adverse events among 254 at risk. Six serious-event terms are listed, each with a recorded frequency of 0.4%. A death count is not reported in the registry record.