Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery (NCT01297959), a randomized phase 3 study. The primary outcome is Number of Participants In Intent to Treat (ITT) Analysis Set With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving Principal Incision Within 30 Days After Index-surgery as Determined by Blinded Assessors 30 Days Post-operatively.

2. Clinical Question

The clinical question concerns prevention of incisional infection, rather than infection at any surgical site or a broader measure of recovery. The primary endpoint combines superficial and deep incisional infections involving the principal incision. The registry defines these events using clinical signs, microbiological findings, and, for some cases, clinical evidence recorded on the Clinical Infection Wound Scale.

The comparison is between assigned treatment groups. The posted primary counts are 53 participants in the E-101 group and 41 in the saline group, with the analysis denominators listed as 241 and 225, respectively. These are counts of participants meeting the endpoint, not infection episodes. The primary assessment period runs from surgery through 30 days after surgery, and the endpoint title specifies assessment by blinded assessors 30 days post-operatively.

The record also lists other outcomes, including an objectively determined incisional infection measure, an assessment at 14 days, wound-scale scores, and quality-of-life dimensions. Those outcomes can add context, but they do not replace the prespecified primary question. The registry record does not report the protocol rationale for choosing this endpoint or how the clinical definitions were selected.

3. Trial Design

The registry describes a phase 3, randomized, double-masked, parallel-group trial. It compared topical E-101 Solution 300 GU/mL with matched saline solution in participants undergoing colorectal surgery. Enrollment is listed as 503. The record lists a start date of 2013-01-10, primary completion on 2015-10-14, and trial status as completed.

In a randomized design, assignment to the treatment groups is intended to reduce systematic differences in participant characteristics that could otherwise influence the outcome. Double masking is intended to limit the influence of treatment knowledge on participant care, outcome assessment, or reporting; the registry record does not provide further detail about who was masked or how masking was maintained. The parallel-group model means that participants were assigned to one treatment group rather than crossing between treatments.

The E-101 and saline descriptions both specify topical application twice to the surgical wound. The recorded E-101 concentration is 300 GU/mL. Some procedural details in the arm descriptions end mid-sentence in the registry record, so the complete application procedure is not reported in the registry record. The record describes the comparison treatment as matched placebo saline.

The primary outcome used an intent-to-treat analysis set, with the registry describing exclusions from that set for specified circumstances before surgery, withdrawal of consent, and treatment at site 03-03. The complete wording of the population definition is not reported in the registry record. The primary outcome assessed superficial and deep incisional surgical site infections involving the principal incision through 30 days after surgery, determined by blinded assessors. The reported sponsor analysis used logistic regression and was classified as a superiority analysis. The registry record does not report the original design assumptions, sample-size justification, or full 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Analysis Set included all randomized participants in their assigned treatment group except those were found between randomization and before surgery to either meet exclusion criteria or not meet inclusion criteria, who withdrew consent or were treated at site 03-03 (participants were excluded because of a systematic problem in incisional SSI surveillance due to a lack of blinded assessors). Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

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: Safety analysis set included all participants randomized to treatment and exposed to any quantity of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants In Intent to Treat (ITT) Analysis Set With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving Principal Incision Within 30 Days After Index-surgery as Determined by Blinded Assessors 30 Days Post-operatively, measured over Surgery (Day 0) up to 30 days post-surgery.

The primary endpoint counts participants in the intent-to-treat analysis set who experienced a superficial or deep incisional surgical site infection involving the principal incision from surgery through 30 days post-surgery. The registry describes superficial infection using findings such as purulent drainage, organisms isolated from an incision culture, local signs, or clinical evidence on the Clinical Infection Wound Scale. Deep infection is described using findings that include drainage, fever, local pain or tenderness, wound separation, positive microbiology, abscess, or other clinical evidence.

This endpoint is used because it focuses on infection in the surgical incision itself and captures both superficial and deeper incisional involvement. Counting participants with an event gives a binary outcome for each participant: the endpoint is either met or not met under the registry’s criteria. The endpoint is not a count of all infection episodes, and it does not include every possible postoperative infection.

The registry identifies the outcome as determined by blinded assessors 30 days post-operatively. Blinding can help limit assessment being influenced by knowledge of treatment assignment, although the registry record does not describe the assessment procedures in detail. The record also does not report how any disagreements in classification were resolved.

7. Results Posted in the Registry

• E-101 Solution 300 GU/mL: 22.0% (53/241) versus 18.2% (41/225) on control; risk difference 3.8 percentage points (95% CI -3.5 to 11.0), risk ratio 1.21 (0.84–1.74); unadjusted two-proportion z-test p = 0.311.

8. Secondary Efficacy Endpoints

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

Mean Clinical Infection Wound Scale Score (CIWS)

• 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:
  • E-101 Solution 300 GU/mL: mean 0.40 versus 0.40 on control; difference 0.00 (95% CI -0.21 to 0.21), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between E-101 Solution 300 GU/mL and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI)

• 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:
  • E-101 Solution 300 GU/mL: 13.7% (33/241) versus 11.6% (26/225) on control; risk difference 2.1 percentage points (95% CI -3.9 to 8.2), risk ratio 1.18 (0.73–1.92); unadjusted two-proportion z-test p = 0.488.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between E-101 Solution 300 GU/mL and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving the Principal Incision (PI) Within 30 Days After the Index-surgery as Determined by Blinded Assessors 14 Days Post-operatively

• 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:
  • E-101 Solution 300 GU/mL: 20.7% (50/241) versus 23.1% (52/225) on control; risk difference -2.4 percentage points (95% CI -9.9 to 5.2), risk ratio 0.90 (0.64–1.27); unadjusted two-proportion z-test p = 0.537.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between E-101 Solution 300 GU/mL and the control. The interval gives the range of effects that remain compatible with the data.

The posted numerical secondary outcomes do not point consistently in one direction. The mean Clinical Infection Wound Scale score was 0.4 in both groups. The objectively determined incisional infection outcome had more recorded events in the E-101 group, while the blinded assessment at 14 days had fewer. The unadjusted confidence intervals for these binary comparisons cross no difference, and the mean-score interval also spans no difference.

This mixed pattern is broadly compatible with the uncertainty in the primary result rather than offering a clear, consistent alternative signal. Secondary endpoints may differ from the primary endpoint in how infection is defined, who assesses it, and when it is assessed. The 14-day outcome is labeled as involving infection within 30 days in its title, while its timeframe is listed as surgery through 14 days post-surgery. That distinction makes careful attention to the recorded endpoint wording important.

The registry identifies 18 posted secondary outcomes, including quality-of-life dimensions, but numerical results for many listed outcomes are not reported in the registry record. The available secondary findings therefore cannot support a broad synthesis of every registered outcome.

Multiple outcomes create a multiplicity concern: when many hypotheses are tested, the chance of at least one apparently unusual result can increase even if there is no real effect. Whether and how to adjust interpretation depends on the analysis plan and the role assigned to each endpoint. The registry record does not report a multiplicity strategy. Accordingly, unadjusted secondary results carry less weight than a prespecified primary analysis and should be treated as exploratory context rather than independent proof.

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

• Mean Clinical Infection Wound Scale Score (CIWS)
• Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI)
• Number of Participants With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving the Principal Incision (PI) Within 30 Days After the Index-surgery as Determined by Blinded Assessors 14 Days Post-operatively
• Worst Post-Baseline Mobility Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
• Worst Post-Baseline Self-Care Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
• Worst Post-Baseline Usual Activity Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
• Worst Post-Baseline Pain/Discomfort Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
• Worst Post-Baseline Anxiety/Depression Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either met the registry’s infection definition during the assessment period or did not. The posted group summaries therefore include an event count and an analysis denominator for each treatment group. Comparing event proportions is a natural way to describe the difference between two groups for this kind of outcome.

What does the risk difference express?

The risk difference is the event proportion in the E-101 group minus the event proportion in the saline group. A value above zero indicates a higher observed event proportion in the E-101 group; a value below zero indicates a lower one. The recalculated estimate for the primary outcome is 0.038. This is a difference on the proportion scale, not a relative comparison. It is based on the posted counts and denominators and is not adjusted for other participant characteristics.

What does the confidence interval add?

A confidence interval describes statistical uncertainty around an estimated effect under the assumptions of the method used. It gives a range of effect values compatible with the observed data and that method. For the primary risk difference, the interval is -0.035 to 0.110. Because it crosses zero, the posted summary statistics do not rule out no difference, nor do they rule out effects in either direction. An interval is not a guarantee that the true value lies within its limits, and it does not account automatically for design or measurement limitations.

How should the p-value be read?

The unadjusted p-value for the recalculated primary comparison is 0.311. A p-value measures how unusual data at least as discrepant as those observed would be under a specified null model, given the assumptions of the test. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. The registry reports a different p-value, 0.39, from its logistic-regression analysis. The two values come from different analyses and should not be treated as interchangeable.

What does logistic regression contribute?

Logistic regression models the relationship between a binary outcome and treatment assignment, and can also incorporate other variables if those are included in the model. The registry identifies logistic regression as the sponsor’s method but does not report model covariates, coding details, or diagnostics. The reported analysis is classified as superiority. Since the model details are not reported in the registry record, the sponsor’s result cannot be fully reconstructed from the posted summary counts alone.

Why distinguish absolute and relative comparisons?

Risk differences describe absolute separation on the proportion scale. Risk ratios and odds ratios describe relative contrasts, but their interpretation differs from that of a risk difference. Relative measures can be useful in some settings, yet they can appear larger or smaller depending on the baseline event frequency. The registry’s reported analysis is logistic regression, while the simple recalculation is unadjusted and based on group summaries. The recalculation is therefore a descriptive statistical supplement, not a substitute for the sponsor’s model.

Why can event rates vary across endpoints?

Outcome definitions and assessment times matter. The primary endpoint concerns superficial and deep incisional infection involving the principal incision through 30 days. Other posted outcomes use different ascertainment labels or timeframes. A broader or differently assessed endpoint can classify participants differently. These distinctions mean that secondary endpoint results should be interpreted according to their own definitions rather than as direct replicas of the primary result.

General statistical context: randomization supports a comparison of assigned groups, but it does not remove uncertainty from finite samples, incomplete follow-up, or outcome classification. Masking may reduce some assessment and performance biases, but it cannot guarantee that all sources of bias are absent. The registry record does not report enough detail to evaluate every assumption of the sponsor’s model or the handling of incomplete outcome data.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.038, with a confidence interval from -0.035 to 0.110. The interval includes zero and extends to values on both sides of it. This means the posted data are compatible with no difference as well as with an increase or decrease in the event proportion under the unadjusted analysis. The estimate alone should not be read as a precise measure of the underlying treatment contrast.

Confidence intervals are useful because they show the range of estimates that remain reasonably compatible with the observed data and the analysis assumptions. They do not indicate that every value within the range is equally likely, and they do not capture uncertainty due to unreported design choices, missing outcome information, or possible errors in measurement. The registry record does not provide a confidence interval for the sponsor’s logistic-regression estimate.

For the secondary binary comparisons, the recalculated intervals also cross zero: this is true for the objectively determined infection comparison and the assessment at 14 days. The mean Clinical Infection Wound Scale comparison has an interval from -0.208 to 0.208. These intervals reinforce that the secondary estimates are not precise enough to establish a clear difference from the posted summaries.

Precision is distinct from whether a result crosses a conventional significance threshold. A wide interval may reflect limited information for the size of effect being estimated, while a narrow interval can still include values that matter clinically. The registry record does not report a clinically meaningful threshold for the primary endpoint or an equivalence margin, so the interval cannot be used to establish equivalence or to decide clinical importance.

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 are based on the observed primary effect and express the number of participants per arm, not a combined trial total or a total number of events. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. Each scenario targets the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

For planning around 100% of the observed effect, the illustration gives 1,774 participants per arm for 80% power and 2,374 participants per arm for 90% power. For 75% of the observed effect, it gives 3,099 participants per arm for 80% power and 4,148 participants per arm for 90% power. For 50% of the observed effect, it gives 6,845 participants per arm for 80% power and 9,163 participants per arm for 90% power.

In plain terms, the 80% power column represents the planned group size under the stated assumptions for a design with an 80% chance of detecting the specified effect using the stated test. The 90% power column uses a higher target chance of detection, which requires more participants under these assumptions. Smaller effects are harder to distinguish from random variation, so the illustrations require more participants per arm as the target effect becomes smaller.

These are planning illustrations, not observed power. They use the observed effect as an input and do not reconstruct the trial’s original planning. Power calculations are sensitive to assumptions about the effect size, outcome frequency, allocation, and analysis, so the figures should be read as conditional illustrations rather than prescriptions.

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 = 0.182; treatment proportion p₁ = 0.220; average p̄ = 0.201.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5668 = 1.1109.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5662 = 0.4765.
4. n = (1.1109 + 0.4765)² / (0.0377)² = 1,773.5, rounded up to 1,774 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 <- 0.182222222222222                          # control proportion
p1 <- 0.219917012448133                          # 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(1297959)
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 = 1,774 (80% power), 2,374 (90% power)
 75% of observed effect: n per arm = 3,099 (80% power), 4,148 (90% power)
 50% of observed effect: n per arm = 6,845 (80% power), 9,163 (90% power)
power.prop.test: 1773.5 
Simulated power at n = 1,774 per arm: 0.801 (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 registry reports that the sponsor used logistic regression for a superiority analysis of the primary endpoint, with p = 0.39. The unadjusted recalculation from the posted group counts gives p = 0.311. These are different analyses: logistic regression is a model-based approach, while the recalculation compares the posted group summaries without adjustment. Different methods can yield different p-values even when applied to the same trial.

The sponsor’s analysis is the trial’s reported inferential result. The registry record does not provide the regression model’s covariates, full specification, or associated estimate and confidence interval, so its result cannot be recreated from the group counts alone. The record does not identify a discrepancy between the sponsor analysis and the recalculation. The recalculated result should therefore be used as a transparent, unadjusted companion to—not a replacement for—the sponsor’s analysis.

Both p-values are above the conventional 0.05 significance level used in the planning illustrations, but that comparison alone does not establish that the groups are equivalent. The effect estimate and its interval are also important: the primary interval crosses no difference and includes effects in either direction. The sponsor’s reported p-value does not quantify the range of plausible effects, and the registry record does not report the sponsor-model confidence interval.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and multiple secondary outcomes, but it does not report a multiplicity procedure for controlling the risk of false-positive findings across those analyses. Without a stated hierarchy, adjustment method, or other prespecified strategy, secondary p-values should not be interpreted as if each were the sole confirmatory test. This matters especially when several outcomes, timepoints, or definitions are considered.

The registry reports a sponsor logistic-regression analysis for the primary superiority comparison, but the full statistical analysis plan is not reported in the registry record. Details not reported include the model specification, any covariate adjustment, and the planned handling of outcome data that were unavailable or unevaluable. The record also does not report interim analyses or stopping rules; their absence from the record should not be taken as proof that none occurred.

The primary population is described as an intent-to-treat set containing randomized participants, subject to listed exclusions before surgery, consent withdrawal, and site 03-03. The registry’s population description is incomplete, so the exact application of these exclusions is not fully reported. The primary group denominators are 241 and 225, while the adverse-event at-risk counts are 248 and 234; these correspond to different recorded analysis populations and should not be treated as interchangeable.

The registry record does not report the amount or pattern of missing primary outcome data, whether outcomes were imputed, or whether sensitivity analyses assessed the effect of missingness. Missing outcomes can matter if their likelihood or handling differs between groups. Randomization by itself does not resolve that concern. These omissions limit independent assessment of how robust the reported result is to analysis-population choices and incomplete follow-up.

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: anastomotic leak (3.8%), pneumonia (2.1%), dehydration (2.0%), small intestinal obstruction (1.7%), postoperative ileus (1.7%).

The safety record lists serious adverse events for 57 of 248 participants at risk in the E-101 group and 56 of 234 participants at risk in the saline group. Other adverse events are listed for 180 of 248 and 174 of 234 participants, respectively. These are participant counts from the registry’s safety population, not the primary intent-to-treat denominators. The record lists 2 deaths in each group.

The listed serious-event terms include anastomotic leak at 3.8%, pneumonia at 2.1%, dehydration at 2.0%, small intestinal obstruction at 1.7%, postoperative ileus at 1.7%, and sepsis at 1.6%. The record does not provide enough detail in these summary details to assign those term percentages to a particular group or to assess duration, severity, or relatedness to treatment.

Safety counts are descriptive. They do not by themselves establish whether an event was caused by the study treatment, and differences in counts should not be interpreted without considering definitions, follow-up, and the clinical context. The registry record does not report a comparative safety model or a detailed account of attribution.

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

The posted primary counts and the unadjusted risk-difference interval do not establish a clear difference between topical E-101 and saline for superficial or deep incisional surgical site infection involving the principal incision within 30 days. The estimate points toward a higher observed event proportion in the E-101 group, but its interval crosses no difference and includes values in both directions. The sponsor’s logistic-regression analysis reports p = 0.39.

This result does not show that the treatments are equivalent, nor does it establish that either treatment has no effect. Failure to obtain a statistically persuasive result is not proof of no effect. The confidence interval conveys uncertainty about the size and direction of the difference; the registry does not provide an equivalence margin or a clinical-importance threshold that would support a stronger conclusion.

Secondary outcomes provide additional but mixed context. Their definitions and assessment times differ, and the record does not report a multiplicity strategy. They therefore should not be combined informally into a single conclusion or given the same confirmatory weight as the primary endpoint. Results for several listed outcomes are not reported in the registry record.

The safety summaries report serious adverse events, other adverse events, and deaths in both groups, but do not establish causation or comparative safety. The registry’s concise safety details do not report event attribution, timing, or detailed comparative analyses.

Overall, the record supports a description of the observed data and their uncertainty, not a medical recommendation. It does not establish that E-101 prevents incisional infection, and it does not establish that E-101 cannot do so. Interpretation is limited by the imprecision of the primary estimate and by analysis and follow-up details that are not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why an observed difference and a statistically conclusive difference are not the same thing. The primary counts differ, but the unadjusted confidence interval crosses no difference and extends in both directions. Reporting the estimate alongside its interval is more informative than relying on the event counts or a single p-value alone.

It also highlights the distinction between a sponsor’s model-based analysis and a simple recalculation from posted summaries. The sponsor used logistic regression; the recalculation is unadjusted. Understanding what each analysis estimates, and what details are unavailable, helps prevent treating distinct methods as if they were identical.

Endpoint definition and assessment timing matter. The primary outcome concerns the principal incision through 30 days, while secondary infection outcomes use different descriptions and timeframes. Those distinctions are relevant to how results can be compared and whether secondary outcomes reinforce the primary result.

Finally, planning illustrations based on an observed effect are not a substitute for an original sample-size rationale. Their values depend on explicit assumptions, and smaller effects require larger planning group sizes. The registry does not report the trial’s original design assumptions, the full statistical plan, or a multiplicity approach. These gaps show why statistical interpretation depends not only on the headline result, but also on precision, endpoint definitions, analysis populations, and transparent reporting.

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 does not report the original sample-size justification or the assumptions used to design the trial. The planning illustrations based on the observed effect cannot establish whether the study was originally sized to detect a clinically meaningful difference. No clinical-importance threshold or equivalence margin is reported.

The primary outcome population description is incomplete, and some arm-application instructions end mid-sentence. The record therefore does not fully explain the exclusions from the intent-to-treat set or all procedural details. It also does not report the amount or pattern of missing primary outcome data, any imputation, or sensitivity analyses for missingness.

The sponsor’s logistic-regression result is reported without the model estimate, confidence interval, covariates, or full specification. The recalculation uses posted group summaries and is unadjusted, so it cannot reproduce or validate every aspect of the sponsor analysis. No multiplicity plan is reported despite the range of secondary outcomes.

Secondary outcome information is incomplete: the registry lists additional outcomes, but many numerical results are not reported in the registry record. The 14-day secondary outcome title refers to infection within 30 days, while its stated timeframe ends at 14 days, leaving a wording distinction that should be kept in mind. Safety summaries do not report attribution or detailed comparative analyses, and the serious-event term percentages are not presented with group-specific assignments in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery — NCT01297959.
• Registry record last updated 2021-02-10; status last verified 2021-01.
• Results first posted 2021-01-19.
• 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

NCT01297959 is a completed phase 3 randomized, double-masked, parallel-group study of topical E-101 Solution 300 GU/mL versus matched saline in colorectal surgery patients. The registry lists enrollment as 503. Its primary endpoint counted participants with superficial or deep incisional surgical site infection involving the principal incision through 30 days after surgery.

The posted primary counts were 53 of 241 in the E-101 group and 41 of 225 in the saline group. The unadjusted risk-difference interval crosses no difference, and the sponsor’s logistic-regression analysis reports p = 0.39. Secondary findings are mixed, and the registry record does not report a multiplicity strategy, full analysis plan, or complete missing-data details. Safety summaries list serious adverse events, other adverse events, and deaths in both groups.