This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Multicentre European Study to Evaluate Granulox® Used in the Treatment Pathway of Predominantly Chronic Venous Leg Ulcers (VLUs). (NCT04181320), a randomized na study. The primary outcome is Confirmed Complete Wound Closure.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04181320 |
| Phase | NA |
| Condition | Venous Leg Ulcer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 128 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Molnlycke Health Care AB |
| Results posted | Yes |
2. Clinical Question
Population
People with predominantly chronic venous leg ulcers (VLUs). The brief summary describes a two-week run-in period intended to ensure compliance with compression therapy before randomization. The registry record does not report additional eligibility details or a primary-outcome analysis population.
Intervention
Standard care with Granulox added as an adjunct therapy. The described standard care included wound cleansing, debridement if necessary, a suitable dressing, and compression. Treatment was planned for 20 weeks beginning at randomization.
Comparator
Standard care without Granulox. The arm description says participants received standard-of-care treatment. The registry record does not give further detail about how standard care was tailored or delivered at each site.
Primary question
Whether the two treatment groups differed in confirmed complete wound closure, measured as a count of participants up to 20 weeks after therapy initiation. Closure was defined as 100% re-epithelialization, assessed by a blinded assessor and confirmed at a second visit 15 days later (+/- 3 days). A primary comparison and its result are not reported in the registry record.
3. Trial Design
NCT04181320 is recorded as a randomized, prospective, multicentre European study with a parallel-group design. Its official title describes an open-label comparison of Granulox as an adjunct to defined standard care against defined standard care alone. The record also specifies single masking and describes the study as assessor blinded. These labels indicate that the treatment was not described as fully blinded, while outcome assessment was intended to be blinded; the record does not identify every role that knew treatment allocation.
The study concerned predominantly chronic venous leg ulcers. The brief summary describes a two-week run-in period to support compliance with compression therapy, followed by a 20 weeks treatment period starting with randomization and treatment allocation. The primary outcome timeframe is stated as up to 20 weeks post therapy initiation. The record does not report further detail about the timing of individual visits or any deviations from this planned schedule.
The brief summary says 254 evaluable subjects would be randomized. The registry enrollment is 128. These entries describe different aspects of the record and do not, on their own, explain how many participants were randomized, treated, or included in an outcome analysis. The study status is terminated. The recorded start date is 2020-06-08, and the primary completion date is 2023-01-17. The reason for termination and whether termination affected follow-up or outcome collection are not reported in the registry record.
Standard care was described as wound cleansing, debridement if necessary, application of a suitable dressing, and a compression system until complete wound closure. The registry record does not report site-specific implementation details, adherence results, or a statistical 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
| Stage | Venous Leg Ulcer Standard of Care | Venous Leg Ulcer Standard of Care With Granulox |
|---|---|---|
| STARTED | 66 | 62 |
| COMPLETED | 57 | 57 |
| NOT COMPLETED | 9 | 5 |
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.
| Characteristic | Unit | Venous Leg Ulcer Standard of Care | Venous Leg Ulcer Standard of Care With Granulox | Total |
|---|---|---|---|---|
| Participants analysed | 57 | 57 | 114 | |
| Age, Continuous | years | 70.8 (SD 13) | 69.7 (SD 10.4) | 70.25 (SD 11.8) |
| Sex: Female, Male: Female | Participants | 35 | 33 | 68 |
| Sex: Female, Male: Male | Participants | 22 | 24 | 46 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 54 | 53 | 107 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 3 | 3 | 6 |
| Region of Enrollment: Hungary | participants | 10 | 12 | 22 |
| Region of Enrollment: Czechia | participants | 2 | 3 | 5 |
| Region of Enrollment: Poland | participants | 36 | 37 | 73 |
| Region of Enrollment: United Kingdom | participants | 1 | 0 | 1 |
| Region of Enrollment: France | participants | 3 | 3 | 6 |
| Region of Enrollment: Germany | participants | 1 | 0 | 1 |
| Region of Enrollment: Croatia | participants | 4 | 2 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Confirmed Complete Wound Closure, measured over Up to 20 weeks post therapy initiation.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled Confirmed Complete Wound Closure and is measured as a count of participants. It concerns whether a participant met the specified definition of complete closure during the period up to 20 weeks after therapy initiation. The definition requires blinded assessment and observation of 100% re-epithelialization, with confirmation at a second visit 15 days later (+/- 3 days).
In general, a binary participant-level endpoint records whether each participant meets a defined condition, rather than the degree of change in a continuous measurement. A confirmation visit can make the endpoint definition more explicit by requiring closure to be observed again after the initial assessment. The registry description does not report how missed confirmation visits or ambiguous assessments were handled.
Complete wound closure is a clinically interpretable outcome for a study of ulcer treatment: it describes attainment of the stated closure criterion rather than a change in an intermediate measure. The blinded assessment is relevant because an open-label treatment assignment may be known to participants or treatment staff, while assessor blinding is intended to limit the influence of that knowledge on outcome judgement. The registry record does not report the primary endpoint results, a between-group estimate, or an uncertainty interval. It also flags that the primary outcome has several categories or time points and was not reduced to one comparison, so the endpoint description alone does not establish a single analyzed treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the question and planned comparison, but it does not report a primary efficacy result. It lists no analysis results and indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, the posted record does not establish the number of participants meeting the confirmed-closure definition in each group, the size or direction of a between-group difference, or the precision of such a difference.
The study is recorded as terminated, with enrollment of 128, while its brief summary describes 254 evaluable subjects as the planned number to be randomized. These entries should not be treated as interchangeable measures. Enrollment does not establish the number included in each outcome analysis, and the registry record does not report the reason for termination or a flow of participants through randomization, treatment, and follow-up. It is therefore not possible to determine from these entries alone how the study’s conduct affected its intended comparison.
The design has features intended to support a fair comparison: randomized allocation, a parallel-group structure, and blinded outcome assessment. Randomization can reduce systematic differences between groups at the time of allocation, while assessor blinding can reduce the potential for outcome judgments to be influenced by treatment knowledge. These design features do not substitute for reported results, information on missing outcomes, or a description of the analysis.
In general, an effect estimate is more informative when accompanied by an uncertainty interval and a clear account of the population analyzed. Neither a primary effect estimate nor an interval is reported in the registry record. No p-value or analysis method for the primary comparison is reported either. The listed safety counts are separate from the missing primary efficacy comparison and cannot answer whether the groups differed in confirmed wound closure.
The record supports a description of the intended clinical question and the recorded study status, not a conclusion about the comparative efficacy of the treatments. Because the study was terminated and the outcome comparison is absent, the available entries leave substantial uncertainty about the primary question. No conclusion about treatment benefit or lack of benefit follows from the absence of a reported result.
9. Statistical Methods Explained
The study uses a randomized, parallel-group design. In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences at allocation, although it cannot guarantee that all group characteristics will be balanced, particularly in a study with limited enrollment. The registry record identifies randomized allocation but does not describe the randomization sequence, allocation concealment, stratification, or any other implementation details.
Parallel-group means the groups receive their respective assigned treatment approaches during the study, rather than switching between treatments as part of a crossover design. Here, the comparison is standard care with Granulox as an adjunct against standard care alone. The brief summary describes a compression-therapy run-in followed by treatment. It does not report adherence results or say how participants who did not meet run-in expectations were handled.
The study is described as open-label and assessor blinded. In general, open-label means treatment assignment is not masked from at least some people involved in the study. Blinding the person assessing an outcome can help limit the effect of treatment knowledge on subjective or judgment-based measurements. The record does not specify which other people were masked, how masking was maintained, or whether assessors could infer the assigned treatment.
The primary outcome is binary at the participant level: a participant meets the confirmed-closure criterion or does not. The registry lists the outcome as a count of participants, with a timeframe up to 20 weeks after therapy initiation. In general, analysis of a binary outcome requires a defined denominator and rules for participants whose outcome is unknown or whose follow-up ends before the assessment. Those rules, the analysis population, and the primary comparison are not reported in the registry record.
In general, an effect estimate describes the contrast between groups, while a confidence interval expresses the range of values compatible with the data and the chosen statistical model. A p-value addresses how unusual the data would be under a specified null hypothesis and model; it does not measure clinical importance or the probability that a treatment works. The registry record reports no primary effect estimate, confidence interval, or p-value, and does not identify a statistical model for the primary endpoint. No interpretation of statistical significance for the primary question is therefore possible from the posted results.
Several outcome categories or time points can create multiplicity: testing or selecting among multiple contrasts can increase the chance of a seemingly notable finding unless the analysis plan accounts for that structure. The registry flags multiple categories or time points and says the primary outcome was not reduced to one comparison. It does not report which comparisons were intended, whether any multiplicity adjustment was planned, or how results across time points were to be interpreted. The protocol’s statistical plan and any interim analyses are not reported in the registry record.
The record includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. In general, such calculations explore the sample size associated with assumptions about an effect and a statistical test. They are planning illustrations, not observed power and not evidence that the trial was adequately powered. The record does not report a sample-size justification from the trial’s own design. No calculated planning values are stated in the registry record.
Over-dispersion is relevant in general when observed variation exceeds what a statistical model assumes; ignoring it can make uncertainty estimates too narrow. The endpoint is a participant count, but the registry record does not report a model or dispersion estimate, so over-dispersion cannot be assessed as a feature of the trial analysis. The same caution applies to any unreported adjustment for site or baseline characteristics: the randomized, multicentre description does not establish whether such adjustments were used.
There are no recalculated primary results to compare with a sponsor analysis. The registry record lists no analysis results, and a recalculation from posted summary statistics cannot replace an analysis when the relevant outcome counts and method are absent.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is described as having several categories or time points, and the record flags that it was not reduced to one comparison. That matters because a result can depend on which category, time point, or contrast is selected. In general, examining multiple comparisons without a prespecified strategy can increase the chance that at least one result appears noteworthy by chance. The registry record does not report a multiplicity strategy, a hierarchy of comparisons, or a primary contrast that resolves this issue.
The registry lists one outcome measure, but this does not establish that there was only one statistical test or one analysis. The record reports no analyses. It does not state whether the listed measure was to be assessed at multiple time points, whether analyses were planned for subgroups, or whether any interim analyses occurred. These details are not reported in the registry record.
Missing-outcome handling is also unclear. The record does not describe how participants without an evaluable wound assessment, a missed confirmation visit, or incomplete follow-up were to be classified. It does not report whether missing outcomes were imputed, excluded, or handled through a sensitivity analysis. In general, these choices can affect the estimated comparison, particularly when missingness differs between groups or is related to outcome status.
The primary analysis population is not reported in the registry record. The enrollment entry and the brief summary’s planned number of evaluable subjects do not identify who was randomized or who contributed to the primary outcome analysis. There is no participant-flow account or reported set of analysis populations. Without those details, the scope of any primary result cannot be evaluated; in this case, the primary result itself is not reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Venous Leg Ulcer Standard of Care | 3 | 66 | 4.5% |
| Venous Leg Ulcer Standard of Care With Granulox | 2 | 62 | 3.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Venous Leg Ulcer Standard of Care | 0 of 66 |
| Venous Leg Ulcer Standard of Care With Granulox | 0 of 62 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Venous Leg Ulcer Standard of Care | 6 of 66 |
| Venous Leg Ulcer Standard of Care With Granulox | 7 of 62 |
Most frequent serious adverse event terms
| Event term | Organ system | Venous Leg Ulcer Standard of Care | Venous Leg Ulcer Standard of Care With Granulox |
|---|---|---|---|
| Inflammation of left leg | General disorders | 0 of 66 | 1 of 62 |
| Stroke (thrombotic) | Vascular disorders | 0 of 66 | 1 of 62 |
| Motor deficit of the lower limbs and mechanical fall | Musculoskeletal and connective tissue disorders | 1 of 66 | 0 of 62 |
| Shortness of breath | General disorders | 1 of 66 | 0 of 62 |
| Worsening of coronary artery disease (acute myocardial infarction) | Cardiac disorders | 1 of 66 | 0 of 62 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Venous Leg Ulcer Standard of Care | Venous Leg Ulcer Standard of Care With Granulox |
|---|---|---|---|
| Ulcer | Skin and subcutaneous tissue disorders | 0 of 66 | 3 of 62 |
| Covid-19 infection | Infections and infestations | 2 of 66 | 0 of 62 |
| Deterioration of basalioma on the face | Skin and subcutaneous tissue disorders | 0 of 66 | 1 of 62 |
| Atrial fibrillation | Cardiac disorders | 0 of 66 | 1 of 62 |
| Heart arrhythmia | Cardiac disorders | 0 of 66 | 1 of 62 |
| Inflammation of left leg | General disorders | 0 of 66 | 1 of 62 |
| Flu syndrome | Infections and infestations | 1 of 66 | 0 of 62 |
| Stasis dermatitis | Skin and subcutaneous tissue disorders | 1 of 66 | 0 of 62 |
| Deep vein thrombosis | Vascular disorders | 1 of 66 | 0 of 62 |
| Itching of the body | Skin and subcutaneous tissue disorders | 1 of 66 | 0 of 62 |
Serious events with the highest arm-level rate: inflammation of left leg (1.6%), stroke (thrombotic) (1.6%), motor deficit of the lower limbs and mechanical fall (1.5%), shortness of breath (1.5%), worsening of coronary artery disease (acute myocardial infarction) (1.5%).
The registry reports serious adverse event counts and other adverse event counts separately for the two groups. For standard care, 3 serious adverse events are listed among 66 at risk, and 6 other adverse events among 66 at risk. For standard care with Granulox, 2 serious adverse events are listed among 62 at risk, and 7 other adverse events among 62 at risk. Deaths are recorded as 0 in each group.
These are counts, not a complete account of event timing, duration, severity beyond the serious classification, or relationship to treatment. The registry does not report an analysis comparing safety between groups, and no comparative risk estimate or uncertainty interval is available. The counts alone should not be interpreted as evidence that one treatment is safer than the other.
The listed serious adverse event terms include inflammation of left leg and stroke (thrombotic), each recorded as 1.6%; motor deficit of the lower limbs and mechanical fall, shortness of breath, and worsening of coronary artery disease (acute myocardial infarction), each recorded as 1.5%. The record does not assign these listed terms to a particular treatment group in this summary. Their percentages therefore should not be used to infer a group-specific frequency. The registry record also does not provide further information about causality or participant-level overlap.
12. What the Result Does, and Does Not, Mean
The record documents a randomized study comparing Granulox added to standard care with standard care alone for predominantly chronic venous leg ulcers. Its primary outcome was confirmed complete wound closure, defined by blinded assessment of 100% re-epithelialization and confirmation at a second visit 15 days later (+/- 3 days). This gives a clear description of the intended outcome, but not a reported treatment effect.
The posted results do not include primary outcome counts by group, a comparison estimate, a confidence interval, or a p-value. The record also states that the primary outcome has several categories or time points and was not reduced to one comparison. As a result, the available information cannot quantify how the groups differed in closure or how precisely any difference was estimated. The absence of a reported efficacy result is not evidence that the treatments were equivalent, nor is it evidence of a benefit.
The safety entries report serious and other adverse event counts for both groups, along with zero deaths in each group. These entries are descriptive; the record does not report a statistical safety comparison or enough detail to interpret the listed serious-event terms by treatment group. They do not answer the efficacy question.
The study status is terminated. The brief summary describes 254 evaluable subjects as planned, while the registry enrollment is 128. The reason for termination, participant flow, missing outcome handling, and analysis populations are not reported. This limits assessment of how closely the study followed its intended design and how much information was available for the primary endpoint.
In general, a randomized design and blinded outcome assessment can help protect a comparison from some forms of bias, but they do not determine the result. Interpretation requires the outcome data, analysis approach, and relevant uncertainty. Since these are not reported for the primary comparison, the registry record supports description of the trial rather than a conclusion about comparative treatment effects.
13. Why This Trial Matters Statistically
This study raises a practical statistical question: how should an adjunct treatment be evaluated when both groups receive a defined standard-of-care pathway and the primary outcome depends on confirmed wound closure? The randomized, parallel-group design is suited to comparing the two assigned approaches, while assessor blinding is relevant because the endpoint requires a judgment about wound closure.
The study’s reporting also illustrates why a clearly defined endpoint is not enough for statistical interpretation. The closure definition and confirmation visit are specified, but the registry record does not report group-level outcome counts or an analyzed contrast. It also flags several categories or time points without reducing the primary outcome to one comparison. Without a reported estimand and analysis, readers cannot tell which contrast is intended to answer the primary question.
The difference between the stated plan and the recorded enrollment is another important interpretive issue. The brief summary describes 254 evaluable subjects, while the enrollment entry is 128; the record does not explain this difference or the reason for termination. These registry entries make participant flow and analysis-population reporting especially important, but those details are not reported.
More broadly, this record shows that trial design labels, endpoint definitions, and safety counts do not replace transparent results. Statistical interpretation requires a defined comparison, the observed data, an account of missing outcomes, and uncertainty around the estimated effect. The registry record gives useful context about intended treatment and outcome assessment but does not report those primary analysis elements. The limitation is therefore not merely a question of statistical significance: the comparative result itself is unavailable.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is the absence of a reported primary efficacy comparison. The registry describes confirmed complete wound closure, but provides no group-level counts, effect estimate, uncertainty interval, or p-value. It also notes multiple categories or time points and does not identify a single reduced comparison. The primary result cannot therefore be interpreted from the registry record.
The record is marked terminated. It reports enrollment of 128, while the brief summary describes 254 evaluable subjects as planned. It does not explain the termination, reconcile these entries, report the number randomized or followed, or provide participant flow. The number included in a primary analysis and the extent of missing outcome data are not reported.
The registry does not report the statistical analysis plan, the analysis population, handling of missing assessments, or a method for addressing multiplicity. These omissions are particularly relevant to a confirmed endpoint that requires a second visit, because the record does not state how an absent confirmation assessment was treated. The design description also does not provide details about sequence generation, allocation concealment, or how assessor blinding was maintained.
The safety summary contains event counts but no comparative analysis, uncertainty estimates, or group attribution for the listed serious adverse event terms. It does not provide enough detail to evaluate causality, timing, or participant-level overlap. Finally, the registry record does not report whether the planned standard-care pathway was implemented consistently across centres or whether adherence to compression therapy was achieved after the run-in. These limitations restrict interpretation of both efficacy and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Multicentre European Study to Evaluate Granulox® Used in the Treatment Pathway of Predominantly Chronic Venous Leg Ulcers (VLUs). — NCT04181320.
- Registry record last updated 2024-11-08; status last verified 2024-08.
- Results first posted 2024-11-08.
- 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.
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18. Record Summary
NCT04181320 is a randomized, prospective, multicentre European study with a parallel-group design, recorded as open-label and assessor blinded. It compares standard care with Granulox added as an adjunct against standard care alone for predominantly chronic venous leg ulcers. The primary endpoint is confirmed complete wound closure, assessed up to 20 weeks after therapy initiation.
The record describes a two-week run-in and a 20 weeks treatment period. It reports planned 254 evaluable subjects in the brief summary and enrollment of 128. The study is terminated; the recorded start date is 2020-06-08 and primary completion date is 2023-01-17.
No primary efficacy analysis is reported in the registry record. Safety counts are listed for serious and other adverse events, with deaths recorded as 0 in each group. The reason for termination, participant flow, analysis populations, missing-data methods, and statistical analysis plan are not reported.