Study of PXL01 Versus Placebo to Inhibit Adhesion Formation After Flexor Tendon Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of PXL01 Versus Placebo to Inhibit Adhesion Formation After Flexor Tendon Surgery (NCT01022242), a randomized phase 2 study. The primary outcome is TAM2.

2. Clinical Question

The study’s stated objectives were to assess efficacy, safety, and handling of PXL01 in patients with flexor tendon injury in zone I or II. The primary question represented in the posted results is narrower: it concerns the TAM2 endpoint at 12 weeks, rather than every objective named in the study summary. The registry record does not report a result for handling as a distinct outcome.

The comparison is between locally administered PXL01 and locally administered placebo in the setting of flexor tendon repair. It does not compare surgery with no surgery, or one surgical technique with another. The registry reports an enrollment of 138, while the primary endpoint summaries give separate numbers of participants in the FAS population for the two arms. The record does not explain the difference between those enrollment and outcome counts.

3. Trial Design

This was a phase 2, randomized, double-masked, parallel-group study of PXL01 versus placebo. The registry lists 138 participants enrolled and classifies the study as completed. The recorded study start is 2009-12, and the recorded primary completion is 2012-05. The sponsor is Pergamum AB. These registry descriptors establish the broad design and timing but do not supply all of the operational details needed to reconstruct how the trial was conducted.

Both arms received local application after the flexor tendon had been repaired and before the surgical wound was closed. The registry describes placement between the tendon and tendon sheath and around the tendon sheath, with a volume of 0.5 ml for each product. It does not report additional procedural details, such as who prepared or administered treatment, or how masking was maintained in practice. Random allocation and double masking are stated, but the randomization sequence, allocation concealment, and masking assessment are not reported in the registry record.

The parallel-group structure means participants were assigned to one of the two treatments rather than crossing between treatments. The registry lists placebo as the control arm. It does not report the allocation ratio or a protocol-level explanation of the planned group sizes. The primary outcome was assessed at 12 weeks after surgery and is reported for the FAS population. The registry record does not define the FAS population, give a participant flow account, or explain whether the outcome population was specified before analysis.

The registry lists one outcome measure and one analysis. It identifies the primary outcome as a median with full range and identifies ANCOVA as the analysis method for the two-arm comparison. Covariates, model specification, handling of missing observations, and the statistical significance threshold are not reported in the registry record. The presence of an analysis label alone does not reveal those details or establish whether the method followed a prespecified analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: FAS population

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: 3 patients were treated with an incorrect mixture of IMP and were analyzed separately.

6. Primary Endpoint

The registry lists the primary outcome as TAM2, measured over At 12 weeks after surgery.

The primary endpoint, TAM2, is a measure of active motion in the affected digit. It combines total active motion at the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints when the participant actively makes a fist, then subtracts the extensor lag at those joints. The registry reports the endpoint in degrees at 12 weeks after surgery.

In general, measuring movement at the joints involved in tendon function can describe how much active motion is present after repair. Including extensor lag means the measure accounts for a limitation in fully straightening the joints, rather than counting flexion movement alone. Combining the PIP and DIP components gives one endpoint for the affected digit. The registry does not provide further information about endpoint validation, assessment procedures, assessor training, or the clinical interpretation of particular TAM2 values.

The endpoint is reported as a median and full range for each arm. A median describes the middle value in an ordered set of observations; it is not the same as an arithmetic mean. A full range gives the minimum and maximum observed values but does not show how observations are distributed between those extremes. The posted summaries therefore convey the center and overall span of each group’s observed TAM2 values, but they do not provide a confidence interval for either median or for a between-arm contrast.

The registry states that the primary endpoint population was the FAS population. The meaning and membership of that population are not described in the registry record. The outcome is a measured postoperative result at a specified assessment time; by itself, it does not establish the mechanism underlying any group difference or describe outcomes beyond that time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is presented as a median with a full range. In general, the median is the middle observation after values are ordered, making it a summary of location that is less sensitive to extreme observations than the mean. A full range reports the lowest and highest observations. It is useful for showing the overall span, but it does not show the density of values, the presence of clusters, or the uncertainty around the median. The registry does not report an interquartile range or a confidence interval for the group medians.

The registry identifies ANCOVA as the method used for the two-arm primary comparison. In general, analysis of covariance models an outcome in relation to treatment group and one or more covariates. Covariate adjustment can account for measured baseline characteristics included in the model and can affect the estimated treatment contrast and its precision. The registry does not state which covariates were used, whether the reported model included baseline TAM2, how the outcome was modeled, or what estimate was produced. It is therefore not possible to reconstruct the adjusted contrast from the registry’s summary statistics alone.

A p-value is interpreted relative to a null hypothesis and a statistical model. In general, it measures how unusual data at least as inconsistent with that null would be if the null model and its assumptions were correct. It does not give the probability that the null hypothesis is true, nor does it measure the probability that a result will replicate. The reported ANCOVA p-value is 0.886. Because the coefficient and confidence interval are not reported, the p-value cannot communicate the range of effect sizes compatible with the analysis. A confidence interval, in general, gives a range of values that are compatible with the data and model at a stated confidence level; no such interval for the primary contrast is reported.

Group summaries and an adjusted model result answer related but distinct questions. The medians and ranges describe observed TAM2 values by arm. ANCOVA is intended to compare groups through a model, potentially adjusting for covariates. A difference between medians cannot be substituted for the model’s adjusted estimate, and the registry does not provide the model estimate needed to assess how the adjusted and unadjusted comparisons relate. No recalculated contrast or confidence interval is available in the posted primary outcome information.

Model assumptions matter to interpretation. In general, ANCOVA relies on a suitable outcome model and appropriate treatment of covariates; its validity can depend on the functional form used and, depending on the specification, assumptions about residual variation and the relationship between covariates and outcome. The outcome is summarized using medians and ranges, but the registry does not provide the distributional diagnostics or model specification needed to determine how these considerations were handled. It would be inappropriate to infer from the summary format alone that the analysis was invalid or valid.

In general, over-dispersion means that observed variability is greater than a model assumes. When present in an outcome model, it can make standard errors too small if not accounted for, leading to uncertainty estimates that are too narrow. This concept is not itself a finding about this trial: the registry record does not report a dispersion assessment, model diagnostics, or an adjustment for over-dispersion. The primary outcome is a motion measure in degrees, and the record does not describe the detailed distribution or variance model.

Multiplicity concerns arise when multiple outcomes, time points, groups, or analyses are tested. In general, a larger set of tests creates more opportunities for apparently unusual results under null hypotheses, so a prespecified strategy may control the interpretation of multiple comparisons. The registry lists one outcome measure and one reported analysis, and no secondary outcomes are posted. That does not establish that no other analyses were performed. A multiplicity plan, including any planned secondary or subgroup analyses, is not reported in the registry record.

Missing-data handling is also important because an analysis can be affected if outcome availability differs across groups or relates to the outcome. The registry identifies an FAS population but does not define it, report the number of missing primary outcomes, describe imputation, or state how participants without a measured TAM2 value were handled. The enrollment count and the arm-specific primary outcome counts do not by themselves explain participant disposition.

Planning calculations based on an observed effect are not observed power. In general, such calculations illustrate the sample size that a future design might require under stated assumptions, including the effect size chosen, significance level, allocation, and model approximation. They do not establish that the current trial had a particular probability of detecting an effect. The registry record does not report the trial’s own sample-size justification or the assumptions used in its original design. The study’s planned sample-size rationale, interim-analysis plan, and any adaptation rules are not reported in the registry record.

Randomization supports a design in which treatment assignment is intended to avoid systematic differences between arms, while masking can reduce some forms of bias in care and assessment. Those design labels do not guarantee that all sources of bias were removed. Sequence generation, concealment, masking procedures, protocol deviations, and endpoint assessment procedures are not described in the registry record. These missing details limit independent evaluation of the analysis and its assumptions.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an ANCOVA analysis and gives its p-value as 0.886. It does not report the corresponding adjusted effect estimate, confidence interval, model covariates, or detailed specification. The registry’s group-level medians and ranges are descriptive summaries and cannot be used to reconstruct that adjusted ANCOVA estimate without additional information.

No comparable recalculated estimate is available for this primary endpoint in the posted results. Consequently, there is no sponsor estimate and recalculated estimate to compare for agreement or discrepancy. The recorded discrepancy flag is false, but that does not supply a missing model coefficient or uncertainty interval. It means the record does not identify a discrepancy between a sponsor result and a recalculation for this result.

In general, a recalculation from summary statistics would be an unadjusted analysis and could differ from a model-based adjusted analysis because the methods use different information and assumptions. For this outcome, however, the available record does not include the recalculated numerical comparison. The sponsor-reported ANCOVA result is therefore the only reported inferential result for the primary comparison. Its p-value should be interpreted alongside the descriptive summaries and the absence of an adjusted estimate and confidence interval, rather than as a complete account of effect magnitude or precision.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis, with TAM2 as the primary endpoint. It lists zero posted secondary outcomes. This limited set of posted results makes the primary comparison identifiable, but it does not establish that the protocol included no other outcomes, time points, subgroup analyses, or exploratory tests. A multiplicity strategy and a prespecified hierarchy of outcomes are not reported in the registry record.

Multiplicity matters in general when several statistical tests contribute to interpretation: without a plan for handling multiple comparisons, the chance of at least one apparently notable result can increase. The registry’s count of posted measures is not a substitute for the original statistical analysis plan. It is not possible to determine whether any unposted analyses were planned, whether adjustment was intended, or whether the reported ANCOVA was the sole confirmatory test.

The primary outcome is assigned to the FAS population, but the registry does not define FAS or describe the rules for including participants in that analysis. It does not state whether all randomized participants were analyzed in their assigned groups, how treatment discontinuation or protocol deviations were addressed, or how missing TAM2 assessments were handled. No missing-data method or sensitivity analysis is reported in the registry record.

The registry reports enrollment of 138 and primary outcome summaries for 51 participants in the placebo arm and 50 participants in the PXL01 arm. These counts alone do not show how many people were randomized to each arm, how many completed follow-up, or why some enrolled participants are not represented in the primary summaries. A participant flow account and reasons for missing outcome measurements are not reported in the registry record. Therefore, the potential effect of missing data on the estimated comparison cannot be assessed from these entries.

The registry also does not report an interim-analysis plan, stopping rules, or adjustment for repeated looks at the data. These elements should not be presumed to have been present or absent. They are simply not reported in the registry record, limiting assessment of how the final analysis was planned and whether the reported p-value reflects any design-level adjustment.

12. 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: tendon rupture (8.6%), adhesion (resulting in tenolysis) (2.9%), procedural pain (1.5%), allergic urticaria (1.5%), accidental death (1.5%).

The posted safety summaries list serious adverse events affecting 9 of 70 participants at risk in the placebo group and 10 of 65 participants at risk in the PXL01 group. Other adverse events affected 22 of 70 participants at risk in the placebo group and 22 of 65 participants at risk in the PXL01 group. These figures are presented as counts and denominators in the registry; they should not be turned into additional percentages or comparative measures without a specified analysis.

The listed serious adverse event terms include tendon rupture at 8.6%, adhesion resulting in tenolysis at 2.9%, procedural pain at 1.5%, allergic urticaria at 1.5%, accidental death at 1.5%, and myeloproliferative disorder at 1.5%. The record does not provide the arm allocation for each listed term, nor does it describe whether terms refer to participants, event episodes, or another reporting unit. Those percentages therefore cannot be assigned to one treatment arm from the posted information.

Arm-level death counts are not reported. Although accidental death appears among the listed serious adverse event terms, the registry does not identify its treatment arm in that listing. The safety summaries are not a complete account of event timing, severity, relatedness assessments, or exposure duration. Counts should be read as registry-reported safety data, not as proof of causation or as a direct estimate of comparative risk.

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

The registry result describes TAM2 values at 12 weeks after flexor tendon surgery in the two study arms. The reported median and full range in each group provide information about observed movement outcomes, while the reported ANCOVA p-value gives an inferential result without the adjusted effect estimate or its confidence interval. Taken together, these entries do not reveal the magnitude and precision of the adjusted treatment contrast.

A large p-value is not evidence that two treatments are equivalent. Equivalence requires an appropriate design and a prespecified margin defining what differences would be considered acceptably small, together with an analysis that evaluates that margin. The registry record does not report an equivalence framework or such a margin. Nor does a non-small p-value prove that a clinically meaningful difference is absent. The uncertainty interval for the adjusted comparison is not reported, so the range of effects compatible with the analysis cannot be assessed.

The endpoint describes active motion in the affected digit’s PIP and DIP joints with extensor lag taken into account. It does not, by itself, capture every dimension of recovery, safety, or treatment handling. The study summary names efficacy, safety, and handling as objectives, but the posted primary endpoint result addresses TAM2, and no separate handling result is listed. The safety entries are a distinct type of information and have their own limitations.

The results also apply to the specific trial population and treatment setting represented in the registry: flexor tendon injury in zone I or II, with local administration after tendon repair and before wound closure. The record does not report enough detail about participant characteristics, sites, surgical practice, or the FAS definition to assess how broadly the findings may apply beyond the trial. The data do not establish outcomes at other follow-up times, because the primary endpoint is reported at 12 weeks.

Accordingly, the posted results support a cautious description of the observed group summaries and the sponsor-reported analysis output. They do not establish that PXL01 changes TAM2, that the treatments are equivalent, or that there is no clinically relevant difference. They also do not by themselves determine the balance of benefits and harms. Those conclusions would require effect estimates with uncertainty, fuller methods and population details, and an assessment of the complete outcome and safety record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it combines descriptive summaries with a model-based comparison while leaving important pieces of the model result unreported. Readers can see the median and full range of TAM2 in each arm, but cannot see the adjusted contrast or its confidence interval. That distinction illustrates why a p-value alone is an incomplete report of a treatment comparison: it does not convey the estimated size of the effect or the precision with which it was estimated.

The endpoint summaries and the ANCOVA result are not interchangeable. The first describe the observed outcome distributions in the two groups; the second is a model-based test. Without the model estimate, covariates, and specification, readers cannot determine how adjustment changed the comparison or independently assess the analysis. The registry’s reporting therefore highlights the value of presenting effect estimates and uncertainty intervals alongside test results.

The record also makes analysis-population transparency important. It identifies the FAS population but does not define it, and the primary outcome counts do not account for all enrolled participants. A flow of participants, reasons for missing outcomes, and explicit analysis rules would help readers understand exactly which observations inform the primary result and how robust it may be to missingness.

Finally, safety reporting requires context. Some serious adverse event terms are presented as percentages without arm-specific assignment, while the overall serious event counts are given by arm. Readers need clear denominators, event definitions, and treatment allocation to interpret those entries. These reporting considerations matter beyond this study: statistical conclusions depend not just on tests and summaries, but also on how populations, outcomes, missing observations, and adverse events are defined.

15. 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 details needed to assess the primary result are not reported in the registry record. The ANCOVA estimate, confidence interval, covariates, and model specification are absent, so the adjusted effect size and its precision cannot be evaluated. The descriptive endpoint summaries do not supply those missing model results. The p-value alone cannot resolve that limitation.

The FAS population is named but not defined. The registry does not provide a participant flow account that reconciles enrollment with the arm-specific primary outcome counts, or explain missing assessments and exclusions. Without those details, the analysis population and possible influence of missing data remain uncertain.

The registry does not report the original sample-size justification, statistical analysis plan, multiplicity strategy, interim-analysis plan, or procedures for handling protocol deviations. It also does not describe the randomization sequence, concealment, masking procedures, endpoint assessor procedures, or model diagnostics. These omissions do not demonstrate that the procedures were inadequate; they prevent readers from evaluating them from the registry record.

Safety reporting is limited in its detail. The registry gives overall serious and other adverse event counts by arm and lists serious event terms with percentages, but it does not assign those terms to treatment arms or provide event timing and relatedness details. Death counts by arm are not reported. Consequently, these entries do not support a complete arm-by-arm assessment of individual serious event types.

The primary outcome is reported at 12 weeks after surgery, and the registry does not provide a primary TAM2 result at other time points. The record also does not report a separate handling outcome, despite naming handling in the study objectives. These limitations constrain interpretation of the scope, precision, and completeness of the posted findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of PXL01 Versus Placebo to Inhibit Adhesion Formation After Flexor Tendon Surgery — NCT01022242.
• Registry record last updated 2014-05-29; status last verified 2014-04.
• Results first posted 2014-05-29.
• 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.

19. Record Summary

NCT01022242 is a completed phase 2, randomized, double-masked, parallel-group study sponsored by Pergamum AB. It enrolled 138 participants and compared local PXL01 with local placebo after flexor tendon repair. The registry records a start of 2009-12 and primary completion of 2012-05.

The primary outcome was TAM2 in degrees at 12 weeks after surgery, reported as a median and full range for the FAS population. The placebo group had a median of 108 degrees, with a full range from 36 to 175 degrees, among 51 participants. The PXL01 group had a median of 121 degrees, with a full range from 29 to 182 degrees, among 50 participants. The reported ANCOVA p-value was 0.886; no adjusted estimate or confidence interval is reported.

The registry also reports arm-level overall adverse event counts and a list of serious adverse event terms. It does not define the FAS population, explain missing primary outcome data, or provide detailed methods for the primary model or safety-term allocation.