Investigation of New Intermittent Catheter Swelling Media in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of New Intermittent Catheter Swelling Media in Healthy Volunteers (NCT04633291), a randomized na study. The primary outcome is Overall Discomfort During Nurse Catheterization.

2. Clinical Question

3. Trial Design

This was a randomized, single-blinded, crossover investigation of two catheter swelling media in healthy volunteers. The study enrolled 22 participants and is listed as completed. The registry record gives a start date of 2019-11-05 and a primary completion date of 2019-11-28. The sponsor was Coloplast A/S.

Each participant underwent catheterization with both the novel swelling media and the comparator swelling media, as described by the crossover design and the two intervention descriptions. A trained nurse performed catheterization. The comparator was the original swelling media in a CE-marked SpeediCath standard male catheter; the novel media was used in a SpeediCath standard male catheter. The study is listed as randomized and single blinded, but who was blinded is not reported in the registry record.

The primary endpoint was overall discomfort during nurse catheterization, assessed immediately after the procedure, up to 5 min. Secondary outcomes covered insertion and withdrawal discomfort, discomfort after urination, handling during insertion and withdrawal, touch of the coating, and visible or microscopic blood. The registry record lists 9 outcome measures and 9 analyses, while 8 secondary outcomes are posted. Further details of the crossover sequence, washout or spacing between catheterizations, randomization procedure, and the 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.

Before assignment: The 22 recruited participant were randomized into the two intervention arms, i.e., using a randomization sequence of two. No participants were excluded and none were discontinued. Thus, 22 participants constituted the safety and the intention to treat (ITT) population.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The intention to treat population (full analysis set) constituted all randomized subjects with a valid informed consent who was exposed to at least one product, and with valid information on at least one product with respect to the endpoint.

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 Overall Discomfort During Nurse Catheterization, measured over Immediately after the procedure/catheterization, up to 5 min..

The primary endpoint was overall discomfort during the entire nurse-performed catheterization procedure. Participants rated their experience on a Visual Analogue Scale, a straight line measuring 10 cm. The ends represented no discomfort or pain at 0 cm and the worst discomfort or pain imaginable at 10 cm. A participant marked the point that matched the experienced sensation; higher scores represented worse discomfort.

The rating was collected immediately after catheterization, up to 5 min, and was summarized as a mean with a standard deviation. This type of endpoint gives a continuous measure of subjective experience rather than reducing responses to categories. It can capture degrees of discomfort across participants, while the mean describes the group’s average score and the standard deviation describes variation among scores.

Overall discomfort is used as the primary endpoint because it assesses the experience of the procedure as a whole. It is distinct from the secondary ratings of insertion discomfort, withdrawal discomfort, and discomfort after urination, which address narrower parts of the experience. As a self-reported measure, the VAS records participants’ perceptions; it is not a direct measurement of tissue injury or a clinical diagnosis.

7. Results Posted in the Registry

• Novel Swelling Media: mean 1.75 versus 1.79 on control; difference -0.04 (95% CI -1.06 to 0.98), standardized effect d = -0.02; z-test p = 0.939.

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.

Insertion Discomfort During Nurse Catheterization

• 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:
  • Novel Swelling Media: mean 2.17 versus 2.03 on control; difference 0.14 (95% CI -0.99 to 1.27), standardized effect d = 0.07; z-test p = 0.807.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Novel Swelling Media and the control. The interval gives the range of effects that remain compatible with the data.

Urination Discomfort After Catheterization

• 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:
  • Novel Swelling Media: mean 0.52 versus 0.37 on control; difference 0.15 (95% CI -0.24 to 0.54), standardized effect d = 0.23; z-test p = 0.446.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Novel Swelling Media and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several parts of catheterization and the immediate experience afterward, alongside handling and blood assessments. For the posted continuous discomfort outcomes, the mean scores for novel and comparator media are close in absolute terms, and the unadjusted comparisons do not indicate clear statistical separation. These observations are broadly consistent with the primary endpoint’s close group averages, but they do not substitute for the primary analysis.

The secondary assessments address distinct questions rather than repeated measurements of one single construct. Insertion discomfort, discomfort after urination, withdrawal experience, handling, coating touch, and blood observations should not be collapsed into a single overall claim. The registry record lists 8 secondary outcomes as posted, including outcomes for which numerical results are not included in the analysis details. Their detailed results therefore cannot be characterized beyond what is reported.

The secondary p-values are unadjusted. General statistical explanation: testing multiple outcomes creates more opportunities for chance findings, so a nominally notable result among many tests can be less persuasive than a single prespecified primary test. No multiplicity adjustment or hierarchy for secondary outcomes is reported in the registry record. The secondary results should consequently be read as supportive or exploratory, with less weight than a well-specified primary analysis.

Because the registry record does not describe the complete analysis plan, it is not possible to determine whether the posted secondary outcomes were selected from a larger set or how missing measurements were handled. Their relationship to the primary finding is therefore contextual: they add dimensions of the catheterization experience, but do not resolve the uncertainty around the primary estimate or establish a broader conclusion.

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

• Insertion Discomfort During Nurse Catheterization
• Withdrawal Discomfort During Nurse Catheterization
• Urination Discomfort After Catheterization
• Catheter Handling During Insertion
• Catheter Handling During Withdrawal
• Touch of Catheter Coating
• Visual Blood During Catheterization
• Microscopic Blood in Catheter-collected Urine

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a VAS score measured in centimetres. The registry record reports each group’s mean and standard deviation. A mean is the arithmetic average of the observed scores; a standard deviation describes how spread out individual scores are around that average. These summaries are useful for describing the outcome, but they do not by themselves capture all features of a crossover analysis.

What does the simple re-calculation represent?

The simple re-calculation compares posted summary statistics for novel and comparator media. Its mean difference is expressed as novel minus comparator, so the estimate of -0.04 cm corresponds to posted means of 1.75 cm and 1.79 cm, respectively. The associated p-value is unadjusted. This calculation is a summary-statistic comparison, not the sponsor’s mixed-model analysis of final values. The registry record does not provide the participant-level data or enough model details to reproduce the sponsor’s analysis.

General statistical explanation: a p-value measures how surprising data at least as incompatible with a specified null hypothesis would be under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, and a large p-value does not prove no difference. A p-value also does not quantify the range of effect sizes compatible with the data; that is the role of a confidence interval.

Why does the crossover design matter?

In a crossover study, participants receive both conditions, so observations from the same person may be related. General statistical explanation: accounting for that within-person relationship can improve or change the precision of a comparison, depending on the design and the correlation between measurements. The sponsor analysis is described as a mixed-model analysis, which is a modeling approach capable of representing structured or repeated observations. The registry record does not report the model specification, terms included, handling of period or sequence, or assumptions about within-participant correlation.

The simple re-calculation uses posted summary statistics and does not reproduce those model details. It is therefore best read as an unadjusted numerical comparison, not as a replacement for the reported model. The difference between the reported and recalculated estimates also reinforces the need to keep the contrast direction and method in view.

What does non-inferiority require?

General statistical explanation: a non-inferiority analysis asks whether the data rule out a disadvantage larger than a prespecified acceptable margin. That margin must be specified before interpreting the result, and the confidence interval is assessed in relation to it. The registry record labels the sponsor’s mixed-model analysis as non-inferiority but does not report the margin or the full testing plan. The label alone is not enough to determine whether the criterion was met.

The sponsor analysis reports a 95% confidence interval from -0.50 to 0.58 cm and p = 0.88. Those are the reported model results; a p-value by itself does not indicate whether a non-inferiority margin has been crossed. The registry record does not report whether an additional analysis population or sensitivity analysis was used for the non-inferiority assessment.

How should the secondary tests be read?

The registry record lists 9 outcome measures and 9 analyses, with 8 secondary outcomes posted. The posted secondary outcomes include continuous discomfort scores and other assessments relating to handling, coating touch, and blood. The unadjusted p-values are not reported as having been corrected for multiple comparisons. General statistical explanation: when many outcomes are tested, the chance of seeing at least one apparently unusual result by chance can increase. Without a reported multiplicity strategy, secondary findings are more appropriately treated as exploratory than as independent confirmatory evidence.

The record states the primary endpoint population as an intention-to-treat population with valid consent, exposure to at least one product, and valid information for at least one product. Details on missing outcome data, exclusions, and how incomplete crossover observations were handled are not reported in the registry record. Those details matter because analyses can be affected if missingness or exclusions are related to outcomes or treatment sequence.

11. Confidence Intervals and Precision

The sponsor’s mixed-model estimate for the primary endpoint was 0.04 cm, with a 95% confidence interval from -0.50 to 0.58 cm. A confidence interval describes a range of values compatible with the data and model, subject to the method’s assumptions. It gives more information about uncertainty than the point estimate alone. Here, the interval includes values on either side of zero, so the reported model results do not precisely determine the direction of the difference.

The simple unadjusted re-calculation gives a mean difference of -0.04 cm and p = 0.939. Its calculation differs from the sponsor’s mixed model, and the registry record does not provide a confidence interval for the recalculation rounded to no more than 3 decimal places. The reported sponsor interval should be interpreted in the context of its model, while the recalculated estimate is a separate summary-statistic comparison.

General statistical explanation: a narrower confidence interval indicates greater precision, while a wider interval leaves more uncertainty about the size of an effect. Precision depends on such features as the amount of information, variability, and analysis assumptions. The study had 22 participants, and both posted group summaries include 22 observations. The registry record does not give enough detail to assess how the crossover correlation or incomplete observations affected the model’s precision.

The interval is not a range containing 95% of individual participants’ scores, and it does not imply that every value inside it is equally plausible. Nor does an interval that includes zero prove equivalence. In a non-inferiority analysis, precision must be judged against the prespecified non-inferiority margin; that margin is not reported in the registry record.

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 figures are participants per arm, not total events. They are planning illustrations computed from the observed effect, not the trial’s own design calculations. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column indicates the planned number of participants per arm under those assumptions for an 80% chance of detecting the specified effect if it is present. The 90% power column gives the corresponding planning number for a 90% chance. These are design targets, not descriptions of what the completed trial achieved. This is not observed power.

Rows planning for 100%, 75%, and 50% of the observed primary effect have the following figures, respectively: 29,063, 51,668, and 116,252 participants per arm for 80% power; and 38,908, 69,169, and 155,629 participants per arm for 90% power. The calculations use the observed effect as a reference, so they should not be treated as a recommended sample size for a future study without a separate design rationale.

Smaller effects require more participants to detect under the same assumptions. The figures are especially sensitive when the observed effect is very small, as it is for the primary mean difference. They do not account for any changes to assumptions, crossover-specific modeling, missing observations, or a non-inferiority margin.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.040; pooled standard deviation σ = 1.721.
2. n = 2 × (1.96 + 0.842)² × 1.721² / -0.040² = 29,062.9, rounded up to 29,063 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
delta <- -0.04                      # observed difference in means
sigma <- 1.72111882216191                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4633291)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 29,063 (80% power), 38,908 (90% power)
 75% of observed effect: n per arm = 51,668 (80% power), 69,169 (90% power)
 50% of observed effect: n per arm = 116,252 (80% power), 155,629 (90% power)
power.t.test: 29063.9 
Simulated power at n = 29,063 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 registry analysis is a mixed-model analysis of mean difference in final values. It reports 0.04 cm, a 95% confidence interval from -0.50 to 0.58 cm, and p = 0.88. The registry record identifies this analysis as non-inferiority. Its contrast direction is not clearly described, so the sign should not be directly compared with the simple re-calculation without noting that the recalculation is defined as novel minus comparator.

The simple re-calculation from the posted group summaries gives a novel-minus-comparator difference of -0.04 cm and p = 0.939. It is an unadjusted summary-statistic calculation and does not reproduce the sponsor’s mixed model. Differences in model and contrast definition can affect the estimate and inference; the registry record does not give sufficient model detail to reconcile them further.

The sponsor’s own analysis is the reported inferential analysis for the trial, while the re-calculation is supplementary. The discrepancy field is false, so the record does not identify a disagreement requiring a recalculated result to take precedence. The non-inferiority margin and full statistical plan are not reported in the registry record, preventing an independent assessment of the non-inferiority criterion.

15. Multiplicity, Missing Data and Analysis Populations

The record lists 9 outcome measures and 9 analyses, and 8 secondary outcomes are posted. It does not report a multiplicity adjustment, a hierarchy for testing secondary outcomes, or a broader prespecified testing strategy. When several outcomes are examined, isolated results can arise by chance more often than in a single test. General statistical explanation: multiplicity procedures can limit this issue by adjusting interpretation or controlling an overall error rate. Without a reported procedure, the secondary p-values should be treated as unadjusted.

The primary analysis population is described as an intention-to-treat population: randomized subjects with valid informed consent, exposure to at least one product, and valid endpoint information on at least one product. This definition does not mean every randomized participant necessarily contributed observations for both products. The registry record does not report the number with complete paired measurements, reasons for missing data, imputation methods, or sensitivity analyses for missing outcomes.

The sponsor’s primary analysis is described as a mixed-model analysis, but its specification is not reported. Details such as how treatment, sequence, period, or participant-level structure entered the model are not reported in the registry record. It is also not reported whether the sponsor used additional populations or sensitivity analyses for the non-inferiority assessment.

The registry record does not report interim analyses or the trial’s original sample-size justification. The planning illustration based on the observed effect is not evidence of the protocol’s design assumptions. These omissions limit the ability to assess prespecification, multiplicity, and robustness. They do not show that a particular procedure was or was not performed; the relevant information is simply not reported in the registry record.

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 0% reporting threshold.

The registry record reports 22 participants at risk in each group for serious adverse events and 0 affected in each group. It also reports 22 at risk in each group for other adverse events and 0 affected in each group. Deaths are reported as 0 in both groups, and no top serious-event terms are listed.

These figures describe the adverse-event entries in the registry record for this study. They do not establish that no symptoms or events of any kind occurred outside the recorded categories, and they do not provide a detailed account of event definitions, surveillance, or follow-up duration. The study involved 22 healthy adult male volunteers and was focused on catheter performance and handling. The small study population and the registry’s limited safety detail constrain how broadly the zero counts can be interpreted.

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

The posted results describe a small randomized crossover study in healthy adult male volunteers comparing novel with original swelling media in intermittent urinary catheters. The primary group means were close: 1.75 cm for novel media and 1.79 cm for comparator media on a scale where higher scores indicate worse discomfort. The simple unadjusted re-calculation gives a mean difference of -0.04 cm. The sponsor’s mixed-model analysis reports a 95% confidence interval from -0.50 to 0.58 cm and p = 0.88.

These results do not establish that the products are exactly equivalent. A lack of clear statistical separation is not proof that there is no difference, and the confidence interval still permits a range of values. The registry record labels the model analysis as non-inferiority, but the margin needed to interpret that analysis is not reported. It is therefore not possible to judge the non-inferiority criterion from the label alone.

The findings concern discomfort and other reported assessments in the specific study population and nurse-performed catheterization setting. They do not establish results for other populations, catheterization contexts, or outcomes not reported. The primary outcome is a participant-rated perception, and it should be understood as such rather than as a direct measure of injury.

The posted adverse-event counts show no affected participants recorded for serious or other adverse events in either group, and no deaths. Those counts are limited by the study size and the detail available in the registry record. Overall, the results are best read as estimates with uncertainty, rather than as a definitive demonstration of equivalence, non-inferiority, or a general clinical effect.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate alone is not enough to interpret a comparison. The posted primary means are close, and the simple re-calculation yields a small difference, but the sponsor’s analysis also gives a confidence interval that spans values on either side of zero. The interval and the analysis assumptions are essential to understanding how much uncertainty remains.

The crossover design also matters statistically because the same participants experienced both products. Analyses need to account appropriately for within-participant structure, and the sponsor reports a mixed-model analysis. Yet the model specification and crossover details are not reported in the registry record. This makes it important to distinguish the sponsor’s analysis from a simple comparison of posted group summaries.

The non-inferiority label is another useful statistical lesson: a non-inferiority conclusion depends on a prespecified margin, not just a small observed difference or a large p-value. Because the margin is not reported, the registry results do not permit a complete appraisal of that claim.

Finally, the secondary outcomes highlight the interpretive challenge of multiple measurements. They add descriptive context across discomfort, handling, and blood assessments, but unadjusted secondary tests carry less confirmatory weight. Together, these features show why trial design, analysis details, precision, and reporting completeness all matter alongside the observed averages.

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 study enrolled 22 healthy adult male volunteers. Results may not describe other populations or settings, and the registry record does not report evidence to assess generalizability beyond this group. The study assessed catheterization performed by a trained nurse, so the posted findings are specific to that context.

The registry record describes a randomized, single-blinded crossover design but does not report who was blinded, the randomization procedure, treatment sequence, period details, or any washout arrangements. It also does not give the sponsor model specification or enough information to reproduce the analysis. These omissions limit assessment of potential period or sequence effects and of how repeated observations were handled.

The non-inferiority margin and the original sample-size justification are not reported in the registry record. Without the margin, the reported non-inferiority label cannot be independently assessed. The sample-size planning illustration based on the observed effect does not supply the missing original design rationale.

Details of missing data, exclusions, complete paired observations, and sensitivity analyses are not reported. Nor are multiplicity procedures for the secondary outcomes described. The registry lists 9 outcome measures and 9 analyses, while 8 secondary outcomes are posted; this limits assessment of the full outcome and analysis plan. The small sample and limited safety detail also mean that zero recorded adverse events should be interpreted narrowly, not as proof that all risks are absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Investigation of New Intermittent Catheter Swelling Media in Healthy Volunteers — NCT04633291.
• Registry record last updated 2023-07-17; status last verified 2022-08.
• Results first posted 2023-07-17.
• 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

NCT04633291 is a completed randomized, single-blinded crossover study sponsored by Coloplast A/S. It compared novel swelling media with original comparator swelling media in a SpeediCath standard male intermittent urinary catheter among 22 healthy adult male volunteers. A trained nurse performed catheterization.

The primary endpoint was overall discomfort during nurse catheterization, measured on a 10 cm VAS immediately after the procedure, up to 5 min. The posted means were 1.75 cm for novel media and 1.79 cm for comparator media. The registry reports a mixed-model non-inferiority analysis with a mean difference of 0.04 cm, a 95% confidence interval from -0.50 to 0.58 cm, and p = 0.88. The non-inferiority margin is not reported in the registry record.

Eight secondary outcomes are posted. The registry reports 0 serious adverse events, 0 other adverse events, and 0 deaths in both groups. Further details on the original sample-size rationale, model specification, missing data, and multiplicity are not reported in the registry record.