A Study to Evaluate the Efficacy and Safety of NexoBrid in Subjects With Thermal Burns: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of NexoBrid in Subjects With Thermal Burns (NCT02148705), a randomized phase 3 study. The primary outcome is Primary Endpoint: Number of Participants With Complete Eschar Removal..

2. Clinical Question

3. Trial Design

The registry record describes a randomized, Phase 3, single-masked study with a factorial model. Its title describes a multicenter, multinational, controlled, assessor-blinded study. It enrolled 175 participants with thermal burns and is recorded as completed. The study started on 2015-05-27, and its primary completion date was 2018-06-12.

Three treatment groups are described: NexoBrid Gel, Gel Vehicle, and Standard of Care (SOC). The primary endpoint compared NexoBrid Gel with Gel Vehicle; SOC was excluded from that endpoint under the stated statistical analysis plan. Secondary outcomes included comparisons with SOC. In the SOC group, investigators could select a combination of surgical and non-surgical eschar-removal procedures according to their judgment. The registry’s use of the factorial model label does not identify the factors in that model or explain how they were incorporated into the analysis; that information is not reported in the registry record.

The study objectives included complete eschar removal, timing of eschar removal, surgical burden, related blood loss, and safety, including wound closure and longer-term cosmesis and function. The posted results contain a primary complete-removal endpoint and secondary results for surgical excision or eschar removal and blood loss. Although time to complete eschar removal is listed as a secondary outcome, its result is not reported in the registry record. Details of the randomization procedure, concealment, masking beyond the assessor description, and the trial’s original sample-size justification are not reported in the registry record.

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: Standard of Care (SOC) is not included as it was pre-specified in the statistical analysis plan that for the primary endpoint, NexoBrid Gel will be compared only to the Gel Vehicle

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: Overall 175 randomized patients are the baseline participants (Full Analysis Set, FAS). Out of the 175, 169 were treated (safety population): 77 In NexoBrid Gel arm, 24 In Gel Vehicle arm (Placebo) and 68 in the SOC arm.

6. Primary Endpoint

The registry lists the primary outcome as Primary Endpoint: Number of Participants With Complete Eschar Removal., measured over post application (post 2 h soaking).

The primary endpoint counted participants with complete eschar removal at the end of the topical agent soaking period. The assessment time is described as post application, post 2 h soaking, and the assessment was made by a blinded assessor. The endpoint compared NexoBrid Gel with Gel Vehicle; the registry states that SOC was excluded from this primary comparison under the statistical analysis plan.

A participant count is a binary outcome: each participant is classified according to whether the specified event occurred. This makes the result interpretable as the proportion of participants in each group who had complete eschar removal, as well as a difference between those proportions. The posted results record complete removal for 70 of 75.0 participants in the NexoBrid Gel group and 1 of 25.0 participants in the Gel Vehicle group.

This endpoint directly addresses the stated objective of comparing complete eschar removal with the Gel Vehicle control. It does not by itself measure time to removal, surgical burden, blood loss, wound closure, cosmesis, function, or overall safety. Those are separate outcomes and require their own results and interpretation. The registry does not report further details about the assessment procedure or how missing primary outcome observations were handled.

7. Results Posted in the Registry

• NexoBrid Gel: 93.3% (70/75) versus 4.0% (1/25) on control; risk difference 89.3 percentage points (95% CI 79.8 to 98.9), risk ratio 23.33 (3.42–159.37); unadjusted two-proportion z-test p = <0.001.

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.

Secondary Endpoint: Number of Participants With Surgical Excision Performed or Eschar Removal for NexoBrid vs SOC (FAS)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • NexoBrid Gel: 4.0% (3/75) versus 72.0% (54/75) on control; risk difference -68.0 percentage points (95% CI -79.1 to -56.9), risk ratio 0.06 (0.02–0.17); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for NexoBrid Gel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Secondary Endpoint: Patient-Level Comparison of Actual Blood Loss (Volume in mL) Related to Eschar Removal for NexoBrid vs SOC (FAS)

• 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:
  • NexoBrid Gel: mean 14.17 versus 814.51 on control; difference -800.34 (95% CI -1,059 to -541.94), standardized effect d = -0.99; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for NexoBrid Gel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the posted secondary outcomes, the overall pattern is consistent with differences between the NexoBrid and SOC groups in the reported eschar-removal-related measures. These outcomes address surgical excision or eschar removal and blood loss, rather than repeating the primary question of complete removal compared with Gel Vehicle. A secondary endpoint on time to complete eschar removal is listed, but its result is not reported in the registry record.

The secondary outcomes provide context for the study’s broader objectives, but they do not independently establish the primary endpoint or cover every objective. In particular, the registry’s stated objectives also include wound closure and longer-term cosmesis and function; results for these are not reported in the registry record. Each outcome has its own definition, timing, and analysis, so a pattern across endpoints should not be treated as though all outcomes measure a single underlying result.

Unadjusted secondary results carry less weight as confirmatory evidence when many outcomes or comparisons are considered. Testing multiple outcomes increases the chance that some results will appear compelling by chance, even if there is no underlying difference for those outcomes. The registry record does not report a multiplicity adjustment or a hierarchy governing secondary tests. Consequently, the secondary p-values should be interpreted as individual unadjusted results, with caution about claims based on selecting a subset of favorable findings. They can be informative alongside the primary result, but they do not replace a prespecified strategy for controlling the interpretation of multiple tests.

Different statistical methods also target different features of the data. The binary secondary result is summarized through participant counts and an odds ratio, while blood loss has both mean-based summaries and a sponsor-reported rank-based analysis. Those estimates should not be combined into a single numerical effect. Together, the posted endpoints suggest a broader comparison was studied, while the limits of the registry record prevent a complete assessment of all planned secondary questions.

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

• Secondary Endpoint: Number of Participants With Surgical Excision Performed or Eschar Removal for NexoBrid vs SOC (FAS)
• Secondary Endpoint: Comparison of Time (Days) to Complete Eschar Removal
• Secondary Endpoint: Patient-Level Comparison of Actual Blood Loss (Volume in mL) Related to Eschar Removal for NexoBrid vs SOC (FAS)

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical summaries are used across the outcomes. They answer related but distinct questions: event counts and risk differences describe binary outcomes, while means and rank-based tests address continuous measurements. General explanations below distinguish those concepts from what is specifically documented for this trial.

Binary outcomes and risk differences

For a binary endpoint, each participant either has the event or does not. The primary outcome is recorded as a count of participants with complete eschar removal. A risk difference subtracts the event proportion in one group from the event proportion in the other, using the stated group order. A value of zero would indicate equal observed proportions; positive or negative values indicate the direction of the difference according to that ordering. The recalculated primary risk difference is 0.893, with a 95% confidence interval from 0.798 to 0.989. This is an unadjusted summary based on the posted counts, not an adjusted estimate from a participant-level model.

Odds ratios compare the odds of an event between groups rather than comparing event proportions directly. Odds and risks are not interchangeable, particularly when an event is common. The sponsor reported an odds ratio for the primary endpoint using Fisher Exact. The recalculated odds ratio is a separate unadjusted calculation. Because the registry’s sponsor-reported and recalculated analyses have different estimates and confidence intervals, each should be identified with its own method rather than blended into one result.

Exact and chi-squared tests

Fisher Exact is a method for testing association in a two-group binary outcome using the observed count structure. It is often useful when event counts are sparse. The sponsor used Fisher Exact for the primary endpoint and reported p < 0.001. A p-value is a measure of compatibility between the data and a specified null model, subject to the test assumptions; it is not the probability that the null hypothesis is true, and it does not measure clinical importance.

The sponsor used a Chi-squared method for the secondary binary comparison involving surgical excision or eschar removal. A chi-squared test compares observed counts with the counts expected under a no-association model. General statistical guidance is that sparse expected counts can make a large-sample chi-squared approximation less reliable; the registry record does not report expected counts or further diagnostic details for this analysis. The sponsor reported p < 0.001 for that endpoint.

Continuous measurements and rank methods

The blood-loss outcome is reported in mL as a mean and standard deviation for each group. A mean summarizes the arithmetic average, while a standard deviation describes the spread of individual measurements around that average. The recalculated mean difference is -800.3 mL, with a 95% confidence interval from -1059.0 to -541.9. This comparison is an unadjusted difference between the posted group means.

The standard deviations are large relative to the group means, which indicates substantial variability in the recorded measurements. In general, a highly variable or skewed outcome can make a mean sensitive to a small number of large observations. The registry does not report the distribution of individual blood-loss values, so the extent of skewness or the influence of extreme values cannot be assessed from the summary statistics alone.

For its own blood-loss analysis, the sponsor used Wilcoxon (Mann-Whitney), a rank-based method that compares the ordering of observations between groups rather than directly testing a difference in arithmetic means. The sponsor records an estimate of 6505.80, with a 95% confidence interval from 5974.41 to 7037.19 and p < 0.001. The registry does not explain the estimate’s sign convention or give enough detail to interpret it as a mean difference. It should not be read as the same quantity as the recalculated mean difference.

Variation, over-dispersion, and interpretation

General: over-dispersion means that outcome variability is greater than a statistical model expects. When a model assumes less variability than the data contain, standard errors may be too small and confidence intervals too narrow. This trial’s posted blood-loss summaries show wide variation, but the record does not report an over-dispersion model or a formal assessment of over-dispersion. The concept is relevant when choosing a model, but it is not a finding documented by the registry.

General: a confidence interval describes a range of estimates compatible with the data and the method under repeated sampling assumptions. It is not a range containing a fixed proportion of individual participant outcomes, and it does not account for unreported sources of bias or analysis choices. Different methods can produce different intervals because they target different quantities or rely on different assumptions.

The statistical analysis plan details beyond the primary comparison are not reported in the registry record. The record also does not report whether adjustment variables were used, whether analyses were stratified, or how any planned interim analyses were handled. These absences matter because the posted summary statistics cannot reveal all features of the analysis that may affect uncertainty or interpretation.

11. Confidence Intervals and Precision

Precision is reflected in the width of a confidence interval: narrower intervals indicate less statistical uncertainty about the estimate under the method used, while wider intervals indicate greater uncertainty. An interval should be read alongside its point estimate and outcome scale. It does not describe the range of individual responses, nor does it account for unreported design or analysis limitations.

For complete eschar removal, the recalculated risk difference is 0.893, with a 95% confidence interval from 0.798 to 0.989. That interval lies above zero, indicating that the observed group difference is not close to equality under this unadjusted calculation. The sponsor’s reported odds ratio interval is much wider than the recalculated odds ratio interval: the sponsor reports 288.281, with limits of 35.549 and 13984.356; the recalculation reports an odds ratio of 336.0, with limits of 37.36 and 3022.0. These are different analyses of the same posted endpoint, and the very wide sponsor interval indicates substantial uncertainty about the magnitude of the odds ratio.

For the secondary binary outcome, the recalculated risk difference is -0.68, with a 95% confidence interval from -0.791 to -0.569. For blood loss, the recalculated mean difference is -800.3 mL, with a 95% confidence interval from -1059.0 to -541.9. These intervals describe unadjusted estimates and do not answer questions about other outcomes, such as time to complete eschar removal, for which a result is not reported in the registry record.

Confidence intervals can be narrow or wide for reasons including the amount of information, outcome variability, and the analysis method. The posted blood-loss standard deviations indicate considerable variability, and the sponsor’s rank-based estimate is not the same target as the recalculated mean difference. Therefore the intervals should be interpreted with their respective methods and estimands in mind. The registry record does not report enough detail to assess all sources of uncertainty, including missing-data handling or multiplicity adjustment.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations give participants per arm for the listed binary and continuous comparisons; they are not total-event counts. The time-to-event convention mentioned in the registry’s planning description is not applicable to these displayed outcomes, and a result for the time-to-complete-removal endpoint is not reported in the registry record. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for each illustration is a stated fraction of the observed effect.

For each effect assumption, the 80% power column gives the illustrative number of participants per arm needed for an 80% chance of detecting an effect of that size under the planning assumptions, if the effect and assumptions were valid. The 90% power column gives the corresponding illustration for a 90% chance. These are prospective planning calculations based on the observed estimates, not the trial’s original design justification. The trial’s own sample-size assumptions are not reported in the registry record.

The rows that plan for 100% of the observed effect use the full observed effect estimate; planning for 75% or 50% of the observed effect represents a smaller effect to detect. Smaller effects generally require more participants for the same target power, which is why the displayed participant requirements rise as the assumed effect becomes smaller. The values are illustrations rather than guarantees: real requirements depend on whether the assumptions, outcome variability, allocation, and analysis method match a future study. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.040; treatment proportion p₁ = 0.933; average p̄ = 0.487.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7069 = 1.3854.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3172 = 0.2670.
4. n = (1.3854 + 0.2670)² / (0.8933)² = 3.4, rounded up to 4 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.04                          # control proportion
p1 <- 0.933333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2148705)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 4 (80% power), 5 (90% power)
 75% of observed effect: n per arm = 7 (80% power), 9 (90% power)
 50% of observed effect: n per arm = 15 (80% power), 19 (90% power)
power.prop.test: 3.4 
Simulated power at n = 4 per arm: 0.937 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s primary analysis used Fisher Exact and reported an odds ratio of 288.281, with a 95% confidence interval from 35.549 to 13984.356 and p < 0.001. The unadjusted recalculation from the posted counts reports an odds ratio of 336.0, with a 95% confidence interval from 37.36 to 3022.0, as well as a risk difference of 0.893 and p < 0.001. Both approaches indicate a large observed difference in complete eschar removal, but the odds-ratio estimates and intervals are not identical.

The recalculation is a simple unadjusted analysis of aggregate counts. The sponsor’s analysis is the registry’s reported trial analysis and should be distinguished from that recalculation; the record does not report a discrepancy flag. For the secondary binary outcome, the sponsor reports a Chi-squared odds ratio of 0.011, with a 95% confidence interval from 0.003 to 0.044 and p < 0.001. For blood loss, the sponsor used Wilcoxon (Mann-Whitney), whereas the recalculation compares arithmetic means. Its reported estimate, 6505.80, is not directly comparable to the recalculated mean difference, and the record does not explain the estimate’s sign convention.

15. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the study adjusted for multiplicity across endpoints or comparisons. It identifies a primary comparison of NexoBrid Gel with Gel Vehicle and states that SOC was not included in the primary endpoint comparison. That distinction identifies the primary contrast, but does not by itself describe how the many secondary outcomes or any additional analyses were handled statistically. Without a reported multiplicity plan, the secondary p-values should not be interpreted as though they necessarily maintain a single overall error rate across all tests.

Missing-data handling for the primary endpoint is not reported in the registry record. The record does not state whether all randomized participants were included in the primary analysis, how participants with unobserved outcomes were treated, or whether any imputation or sensitivity analyses were performed. Secondary outcomes identify a full analysis set (FAS) in their titles, but the definition of that population and its relationship to all randomized participants are not reported in the registry record. The primary analysis population is not reported in the registry record.

There is no reported account of protocol deviations, exclusions from analysis, outcome availability by group, or sensitivity analyses for missing values. These details matter because an analysis of observed outcomes may differ from an analysis that includes every randomized participant, particularly if outcome availability is related to group or outcome status. The aggregate counts alone cannot establish whether missingness occurred or how it might affect estimates.

The record also does not report interim analyses, stopping rules, or the complete statistical analysis plan. No assumptions about these features can be made from the posted endpoint results. The absence of reporting is not proof that an analysis or procedure did not occur; it means its role cannot be assessed from the registry record. These limitations constrain interpretation of nominal p-values and the reproducibility of the reported analyses.

16. 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: infusion site thrombosis (4.2%), seizure (4.2%), phlebitis superficial (4.2%), sepsis (2.6%), wound infection bacterial (2.6%).

Safety counts are reported separately for NexoBrid Gel, Gel Vehicle, and SOC. Serious adverse events are recorded for 9 of 77 participants at risk in the NexoBrid Gel group, 3 of 24 at risk in the Gel Vehicle group, and 9 of 68 at risk in the SOC group. Deaths are recorded as 2, 0, and 0, respectively. Other adverse events are recorded for 49 of 77 at risk, 16 of 24 at risk, and 39 of 68 at risk, respectively. These are descriptive counts; they do not establish that an event was caused by a treatment.

The registry lists serious adverse-event terms including Infusion Site Thrombosis, Seizure, Phlebitis Superficial, Sepsis, Wound Infection Bacterial, and Glioblastoma, with percentages recorded as 4.2%, 4.2%, 4.2%, 2.6%, 2.6%, and 1.5%, respectively. The record does not give an arm-specific breakdown for these listed term percentages in the information, so they should not be assigned to a treatment group. Differences in at-risk counts and the lack of further event detail limit direct comparisons. The registry record does not report event timing, severity beyond the serious classification, or causal assessment for these summaries.

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

The primary result shows a higher observed count of complete eschar removal in the NexoBrid Gel group than in the Gel Vehicle group at the recorded assessment time. The unadjusted risk-difference estimate and the sponsor-reported Fisher Exact analysis both indicate a marked difference in this endpoint. This is evidence about the specific comparison, outcome definition, and assessment period recorded in the trial; it should not be generalized to outcomes that were not measured or reported.

The result does not, by itself, establish how quickly complete removal occurred, how much surgery was avoided, what happened to wound closure, or whether longer-term cosmesis and function differed. The registry lists some of these as study objectives or secondary outcomes, but their results are not all reported. Nor does the primary endpoint settle safety: adverse-event counts and deaths need to be considered separately, with attention to their descriptive nature and the registry’s limited detail.

Randomized allocation and an assessor-blinded assessment are relevant design features, but the registry does not report enough information to assess all aspects of allocation concealment, participant masking, missing data, analysis populations, or multiplicity. Statistical significance is not proof of a causal mechanism, and a small p-value does not quantify the importance of an outcome to participants. Conversely, a confidence interval describes uncertainty in an estimate under a method; it does not remove design limitations or uncertainty about unreported outcomes.

The appropriate interpretation is therefore bounded: the posted evidence supports a difference in the recorded primary endpoint for the trial groups, while important questions about other outcomes, safety attribution, and analysis details remain. The record does not establish a universal effect across all thermal burns, care settings, or patient circumstances, and it does not provide a basis for individual treatment decisions.

18. Why This Trial Matters Statistically

This trial illustrates why the estimand and comparator matter. Its primary endpoint concerns complete eschar removal after topical application and compares NexoBrid Gel with Gel Vehicle. SOC is not part of that primary contrast, even though it is an arm in the randomized study and is used in secondary comparisons. Treating all three groups as interchangeable comparators would obscure the question the primary analysis was designed to address.

It also shows why statistical summaries should be matched to the outcome. Participant counts support risk differences and odds ratios for binary endpoints, while blood-loss means and rank-based methods address different features of a continuous outcome. The sponsor’s rank-based estimate cannot be substituted for a mean difference, and the size of a p-value cannot substitute for an effect estimate or its confidence interval.

The record highlights the importance of precision and reporting. The primary comparison has a clear observed separation, yet the sponsor’s odds-ratio interval is very wide, illustrating uncertainty about the magnitude on that scale. The secondary endpoints broaden the clinical questions, but the absence of a reported multiplicity strategy, missing-data approach, and some outcome results limits how strongly they can be used to support conclusions.

Finally, planning illustrations based on observed effects are not evidence about the trial’s original design or its achieved power. Distinguishing retrospective calculations from planned design assumptions prevents a common misreading of sample-size summaries. Together, these statistical issues help readers separate the endpoint result from broader claims and identify what the registry does and does not establish.

19. 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 registry record provides aggregate endpoint summaries rather than participant-level data. It does not report all details needed to reproduce the analyses, including the primary analysis population, missing-data procedures, covariate adjustment, or the full statistical analysis plan. The randomized design and assessor-blinded description are useful context, but the record does not describe the randomization sequence, allocation concealment, or masking beyond the assessor information.

The primary comparison involves NexoBrid Gel and Gel Vehicle, while SOC is not included in that endpoint. This means the primary result cannot be interpreted as a direct comparison with SOC. SOC procedures could vary according to investigator judgment, so the registry’s description includes a potentially heterogeneous comparator approach; details of the procedures actually used are not reported in the registry record.

Some objectives are not accompanied by posted results. In particular, time to complete eschar removal is listed, but its result is not reported in the registry record. Results for wound closure and longer-term cosmesis and function are also not reported in the registry record. The secondary findings therefore do not cover the full set of stated study objectives.

The blood-loss summaries show substantial variability, while the sponsor used a rank-based method and the recalculation uses group means. These methods do not estimate the same quantity. The record does not report the distribution of individual values or explain the sponsor’s reported rank-based estimate’s sign convention. Safety reporting is also limited: counts are available, but causal assessments, timing, detailed severity, and arm assignment for the listed serious-event percentages are not reported in the registry record.

Finally, multiplicity adjustment and interim analysis procedures are not reported. These omissions do not demonstrate that such procedures were absent; they limit what can be concluded from the registry record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of NexoBrid in Subjects With Thermal Burns — NCT02148705.
• Registry record last updated 2024-07-10; status last verified 2023-06.
• Results first posted 2023-06-27.
• 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.

23. Record Summary

The registry record describes a completed randomized Phase 3 study of NexoBrid in subjects with thermal burns. Enrollment was 175, and the primary completion date was 2018-06-12. The primary endpoint counted participants with complete eschar removal after topical agent soaking and compared NexoBrid Gel with Gel Vehicle, not SOC.

The posted primary counts were 70 of 75.0 participants for NexoBrid Gel and 1 of 25.0 for Gel Vehicle. The sponsor reported a Fisher Exact odds ratio of 288.281, with a 95% confidence interval from 35.549 to 13984.356 and p < 0.001. Secondary results address surgical excision or eschar removal and blood loss compared with SOC; a result for time to complete removal is not reported in the registry record.

The record also includes adverse-event counts. Important interpretive details—including missing-data handling, the primary analysis population, multiplicity adjustment, and several stated outcome results—are not reported in the registry record.