Safety and Tolerability of Seroguard Use: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability of Seroguard Use (NCT03640559), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs).

2. Clinical Question

This is a safety and tolerability question, not a test of whether Seroguard improves a clinical outcome. The primary endpoint counts participants with adverse events. The registry describes safety monitoring through vital signs, laboratory investigations, ECG and USG data, and the incidence of adverse reactions and serious adverse reactions. The posted results list adverse-event counts for both groups, alongside a comparison of the groups.

The record’s brief summary describes the safety profiles as similar. That statement should be read alongside the modest amount of posted outcome information: the trial lists 50 participants enrolled, while the primary outcome has arm denominators of 23 for placebo and 24 for Seroguard. How those denominators relate to enrollment is not reported in the registry record. The posted comparison also has a wide confidence interval, so the observed counts alone do not establish that the groups had equivalent safety profiles.

3. Trial Design

The registry describes a multicenter, randomized, double-blind, parallel-group study with placebo control. It is listed as Phase 1 and was sponsored by Pharmasyntez. The study concerned Seroguard solution in patients undergoing planned laparoscopic cholecystectomy. Its status is completed. The registry records a start date of 2015-05-19 and a primary completion date of 2015-10-04.

Participants were assigned to Seroguard or placebo. The Seroguard arm description gives a concentration of 0.41 g/L and an administration volume of 2.4 mL/kg IP. The placebo is described as saline at 2.4 mL/kg IP. The registry lists 50 participants enrolled; the primary outcome results give denominators of 23 in the placebo group and 24 in the Seroguard group. The record does not explain the relationship between the enrollment figure and the outcome denominators.

The primary outcome is the number of participants with adverse events over 28 days. Safety assessment is described as covering vital signs; blood chemistry, blood counts, coagulation tests and urinalysis; 12-channel ECG data; USG data; and the incidence of adverse reactions and serious adverse reactions. The endpoint description refers to assessments at Visits 1–11, but the timing of each visit is not reported in the registry record.

The registry record does not report the study’s original sample-size justification, detailed allocation procedures, or the statistical methods specified in the protocol. It also does not describe whether interim analyses were planned or conducted. Those details should not be inferred from the posted comparison or from the planning illustrations.

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:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over 28 days.

The primary endpoint is the number of participants with adverse events during a 28-day timeframe. It is a participant-count endpoint: a participant is counted as having an event if an adverse event is recorded, rather than the endpoint being a total count of every event experienced by each participant. The registry lists 16 participants in the placebo group and 17 in the Seroguard group for this outcome.

Safety endpoints are used to describe unwanted events and other safety observations during a study. Counting affected participants gives a direct summary of how many people in each group experienced at least one recorded adverse event. It does not, by itself, describe the severity, duration, timing, or recurrence of every event. Those details require event-level information, which is not fully reported in the primary outcome record.

The assessment description indicates that safety evaluation also included vital signs and several laboratory, ECG, and USG measures, as well as adverse and serious adverse reactions. The posted primary endpoint, however, is specifically the number of participants with adverse events. It should not be treated as a single summary of every listed measurement or as evidence about an unreported efficacy outcome. The registry record does not report separate results for the listed vital-sign, laboratory, ECG, or USG measures in the primary outcome entry.

7. Results Posted in the Registry

• Seroguard: 70.8% (17/24) versus 69.6% (16/23) on control; risk difference 1.3 percentage points (95% CI -24.9 to 27.4), risk ratio 1.02 (0.70–1.48); unadjusted two-proportion z-test p = 0.924.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either is or is not counted as having an adverse event. For a binary outcome, the event proportion is the number of participants with the event divided by the number assessed in the group. The registry lists 16 events among 23 placebo participants and 17 among 24 Seroguard participants. The posted comparison presents a risk difference between the groups. A risk difference is an absolute contrast between event proportions, expressed on the probability scale; zero represents equal observed proportions.

What does the confidence interval describe?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect under the method used to calculate it. A narrow interval indicates greater precision, while a wide interval indicates less precision. For a risk difference, an interval spanning zero allows for effects in either direction as well as no difference. The interval posted for this comparison spans both negative and positive values, so it does not precisely establish the direction or size of the difference.

The registry comparison also reports a two-sided unadjusted p-value of 0.924. In general, a p-value describes how unusual the observed data, or data more extreme, would be under a specified null model and the assumptions of the test. It is not the probability that the null model is true, and it is not a measure of the probability that the result happened “by chance.” A high p-value does not establish equivalence or show that a difference is absent. A formal equivalence or noninferiority conclusion would require prespecified margins and an appropriate design and analysis; those are not reported in the registry record.

Why are other effect measures sometimes used?

Risk ratios compare event proportions as a ratio, while odds ratios compare the odds of the event. These measures express relative rather than absolute contrasts and have different interpretations. The posted comparison includes risk-ratio and odds-ratio summaries as well as the risk difference. Such measures can be useful in describing an association, but none removes the uncertainty arising from the limited outcome information. The registry record does not report a detailed statistical analysis plan for the primary outcome.

The posted comparison is identified as an unadjusted recalculation from summary statistics. In general, an unadjusted comparison describes the groups without controlling for other characteristics. It can be informative as a simple contrast, but it is not interchangeable with a prespecified adjusted analysis. The record contains no posted analysis entry, and it does not report covariate-adjusted estimates, a model specification, or the test used in the original study analysis. The comparison should therefore be understood as the posted summary-statistic calculation, not attributed to a particular protocol analysis.

What can a participant count leave out?

A count of participants with at least one adverse event treats a participant with one event the same as a participant with multiple events for this endpoint. It also does not encode event severity or duration. The registry separately reports serious adverse events, but it does not provide a complete event-level account with timing and recurrence in the primary outcome entry. General statistical interpretation of a binary count should therefore stay focused on the chance of at least one recorded event during the stated timeframe, rather than the total burden of all events.

For safety outcomes, differences in follow-up or missing observations can affect the denominators and the interpretation of observed proportions. The registry record does not report missing-data handling, an analysis population definition, or whether every enrolled participant contributed to this endpoint. It also does not report interim-analysis procedures or the study’s original sample-size assumptions. The available denominators and estimates can be described, but those unreported procedures should not be reconstructed from the results.

Finally, the outcome timeframe is 28 days. General interpretation of an estimate is limited to the observation period and the participants represented in the analysis. The registry record does not report follow-up results beyond that timeframe for this primary endpoint. The posted calculations do not establish long-term risk or resolve uncertainty about rare outcomes.

10. Confidence Intervals and Precision

The risk-difference confidence interval is broad and extends from negative to positive values. This means the posted results are compatible with the event proportion being lower in Seroguard, with little or no difference, or with it being higher. The interval therefore does not identify a precise direction or magnitude of effect. Its width matters alongside the point estimate: a point estimate near no difference does not, by itself, imply that the true difference is known closely.

The unadjusted p-value is 0.924, but that value should not be read as evidence that the groups are identical. A confidence interval conveys a range of estimates consistent with the data and calculation method, while a p-value addresses how the data compare with a null hypothesis. Neither measure establishes equivalence. A conclusion of equivalence would require a defined margin and an analysis designed for that question; these are not reported in the registry record.

Precision is limited by the amount of information in the posted comparison. The outcome denominators are 23 for placebo and 24 for Seroguard, and the outcome is common in both groups. With these data, the confidence interval allows a wide range of differences. The registry record does not report a planned precision target or the sample-size rationale, so it is not possible to assess whether the study was designed to estimate this contrast within a particular margin.

The reported confidence interval concerns the risk difference for the primary adverse-event outcome. It does not quantify uncertainty for every individual safety measure or every serious adverse event term. The results apply to the posted 28-day endpoint and do not provide precision information for longer follow-up.

11. 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 sample-size planning figures are participants per arm, not total events. They are planning illustrations based on the observed effect, not the trial’s original design calculation. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers detecting a stated fraction of the observed effect.

For 100% of the observed effect, the illustration gives 20,420 participants per arm for 80% power and 27,336 participants per arm for 90% power. For 75% of the observed effect, it gives 36,414 per arm for 80% power and 48,748 per arm for 90% power. For 50% of the observed effect, it gives 82,180 per arm for 80% power and 110,015 per arm for 90% power.

In plain language, the 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the specified effect if that effect is present, under the stated assumptions. The 90% power column gives the corresponding planning target for a 90% chance. These are prospective planning quantities, not statements about what the completed trial achieved. Smaller effects require more participants to detect under the same planning framework.

These figures are not observed power. The original trial’s sample-size justification and design assumptions are not reported in the registry record. The illustrations should not be taken as evidence that the study was planned using these targets.

12. 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 = 0.696; treatment proportion p₁ = 0.708; average p̄ = 0.702.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6468 = 1.2678.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6468 = 0.5443.
4. n = (1.2678 + 0.5443)² / (0.0127)² = 20,419.9, rounded up to 20,420 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 <- 0.695652173913043                          # control proportion
p1 <- 0.708333333333333                          # 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(3640559)
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 = 20,420 (80% power), 27,336 (90% power)
 75% of observed effect: n per arm = 36,414 (80% power), 48,748 (90% power)
 50% of observed effect: n per arm = 82,180 (80% power), 110,015 (90% power)
power.prop.test: 20419.9 
Simulated power at n = 20,420 per arm: 0.794 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and does not list posted secondary results. It does not report a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified strategy for controlling error across multiple outcomes or analyses. The endpoint description includes several types of safety assessments, but their presence in the assessment description does not establish how many formal statistical tests were planned or how their results were to be interpreted.

Multiplicity is a general statistical concern that arises when many hypotheses are tested: the chance of at least one apparently unusual result can increase as the number of tests grows. Whether that issue affected this study cannot be determined from the registry record because the full analysis plan and complete set of planned analyses are not reported. The posted primary comparison should not be treated as an adjustment for other outcomes.

Missing-data methods are also not reported in the registry record. The primary outcome lists 23 participants for placebo and 24 for Seroguard, while enrollment is listed as 50. The record does not explain this relationship or say whether any outcome values were missing, how missing values were handled, or whether all participants were analyzed according to their randomized assignments.

The analysis population is not reported in the registry record. It is therefore not possible to determine from the posted results whether the comparison used an intention-to-treat population, a per-protocol population, or another defined set of participants. No conclusion about the handling of protocol deviations or exclusions should be inferred. These omissions limit reproducibility and make it harder to assess whether the analysis followed the originally planned approach.

14. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: misbirth (4.3%), pains in the right supraclavicular area (4.2%), leukocytosis (4.2%), increased blood pressure up to 220/100 mm (4.2%).

The serious-adverse-event figures list 1 affected participant among 23 at risk in the placebo group and 2 among 24 at risk in the Seroguard group. Deaths are listed as 0 in both groups. These counts describe the serious-event entries in the registry and should be distinguished from the primary outcome counts, which include participants with adverse events more broadly.

The registry also lists “Misbirth” at 4.3%, “pains in the right supraclavicular area” at 4.2%, “Leukocytosis” at 4.2%, and “Increased blood pressure up to 220/100 mm” at 4.2% among its top serious terms. The record does not clearly assign these listed terms to a specific group in the summary, so they should not be attributed to either arm on that basis.

Serious-event counts are small, and the record does not provide enough event-level detail to assess timing, relatedness, recurrence, or the clinical course. A zero count for deaths in the posted results means none are recorded in these group summaries; it does not establish the absence of other safety concerns or quantify risk outside the observed study period.

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

The posted results describe adverse events in both randomized groups during a 28-day timeframe. The primary count is 16 participants in the placebo group and 17 in the Seroguard group. The registry’s own brief summary characterizes the safety profiles as similar. The posted comparison does not provide precise evidence for the direction or size of a difference: its confidence interval spans both sides of zero, and the unadjusted p-value is 0.924.

This does not establish that the groups are equivalent. Similar observed counts and a large p-value do not exclude meaningful differences, particularly when the estimate is imprecise. Nor do the results show that one group has a higher safety risk. The most appropriate reading is descriptive: the available counts are close, while uncertainty remains substantial.

The endpoint captures whether participants had an adverse event; it does not summarize every event’s severity, duration, timing, or recurrence. Serious adverse events are reported separately, with 1 affected participant in placebo and 2 in Seroguard, and no deaths listed in either group. Those figures are also limited summaries and should not be taken as a comprehensive account of all safety experiences.

The result applies to the studied participants and the recorded 28-day timeframe. The registry record does not provide longer-term primary outcome results, detailed analysis-population information, or the original statistical plan. It also does not report an efficacy endpoint that would support a conclusion about clinical benefit. The study’s safety findings should therefore not be extended to other populations, settings, or durations without additional evidence.

16. Why This Trial Matters Statistically

This study illustrates a central issue in safety analysis: an observed similarity is not the same as demonstrated equivalence. The event counts in the two groups are close, and the registry’s summary describes similar safety profiles. Yet the confidence interval is broad enough to allow differences in either direction. Statistical interpretation requires attention to that uncertainty, not only to the point estimate or p-value.

It also shows why the outcome definition matters. The primary endpoint counts participants who experienced an adverse event, rather than counting every event episode or weighting events by seriousness. Separate serious-event summaries add a different view, but neither count alone describes the full nature and course of the events. Readers should connect each result to the question that its measure can answer.

Sample-size planning is another important consideration. The registry reports 50 participants enrolled, while the outcome denominators are 23 and 24, and the original sample-size rationale is not reported. Planning illustrations based on the observed effect indicate that much larger per-arm samples would be needed to detect smaller effects under their stated assumptions. Those illustrations are not evidence about the trial’s original design or an estimate of its achieved power.

Finally, the record demonstrates the value of complete reporting. Information on missing data, the analysis population, multiplicity, and the original statistical plan would help readers evaluate the reliability and scope of the comparison. Without those details, the posted results remain a limited, descriptive assessment of the recorded safety endpoint.

17. 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 gives limited information for interpreting the comparison. It lists 50 participants enrolled but reports primary-outcome denominators of 23 in the placebo group and 24 in the Seroguard group; the reason for this difference is not reported in the registry record. Missing-data handling and the analysis population are also not reported, leaving the status of participants outside the outcome denominators unclear.

The endpoint is a count of participants with adverse events over 28 days. The record does not provide complete event-level details for the primary outcome, such as the timing, duration, recurrence, or severity of every event. Separate serious-event summaries are available, but their listed terms do not have a clearly stated group attribution in the summary. The primary outcome entry does not report separate results for each of the listed laboratory, vital-sign, ECG, or USG assessments.

The registry record does not report the original sample-size justification, a detailed statistical analysis plan, or any multiplicity approach. It also does not report whether interim analyses were planned or conducted. There are no posted secondary outcome results or analysis entries. These omissions prevent a full evaluation of prespecification and analytical choices.

The primary outcome timeframe is 28 days, so the posted results do not describe longer-term safety. The trial is listed as Phase 1 and has a total enrollment of 50, which limits how broadly its descriptive findings can be applied. The registry record does not report results that would support a conclusion about efficacy.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety and Tolerability of Seroguard Use — NCT03640559.
• Registry record last updated 2019-05-03; status last verified 2018-08.
• Results first posted 2019-05-03.
• 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.

21. Record Summary

This completed Phase 1 study was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of Seroguard in patients undergoing planned laparoscopic cholecystectomy. The registry lists Pharmasyntez as sponsor, 50 participants enrolled, and a 28-day primary safety outcome. Seroguard was compared with saline placebo.

The primary endpoint was the number of participants with adverse events. The posted counts were 16 of 23 in the placebo group and 17 of 24 in the Seroguard group. The registry’s brief summary describes similar safety profiles. The comparison is imprecise, and the posted results do not establish equivalence or exclude differences in either direction. Serious adverse events were listed for 1 placebo participant and 2 Seroguard participants; deaths were listed as 0 in both groups.

The registry record does not report the original sample-size rationale, detailed analysis plan, missing-data handling, or analysis population. The results are a limited description of safety observations during the stated timeframe.