Urinary Track Infection Prevention After Urogynecological Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Urinary Track Infection Prevention After Urogynecological Surgery (NCT03818321), a randomized phase 2 study. The primary outcome is Incidence of Urinary Track Infection (UTI).

2. Clinical Question

The trial therefore focused on the added comparison of methenamine hippurate against placebo when cranberry supplementation was used in both groups. It did not compare cranberry with no cranberry. Its primary outcome was a count of participants with a UTI, rather than a measure of symptom severity or time until infection. The registry record does not give further detail about how eligible patients were identified, how transient retention was defined, or the diagnostic criteria used at the post-op visit.

3. Trial Design

The registry record identifies this as a phase 2 randomized parallel-group trial with quadruple masking. The brief description characterizes it as randomized, double-blinded, and placebo-controlled. The record does not explain the masking labels or specify which roles were masked. Allocation was randomized, but the method used to generate the allocation sequence and the approach to conceal allocation are not reported in the registry record.

The planned comparison assigned patients to methenamine hippurate with cranberry or placebo with cranberry. Both groups were instructed to start tablets at discharge and take them twice daily for 6-8 days. Methenamine hippurate was specified as a 1 g tablet. The record gives no further information about adherence monitoring, changes to the assigned regimen, or whether patients could receive other UTI-prevention measures during follow-up.

The registry lists enrollment of 185. The posted primary outcome has arm denominators of 93 for methenamine hippurate with cranberry and 89 for placebo with cranberry. The record does not explain the relationship between the enrollment figure and the outcome denominators, so they should be read as different reported quantities rather than reconciled by assumption.

The study start date is 2019-06-17, the primary completion date is 2021-07-01, and the status is completed. The primary outcome was incidence of UTI, assessed at the one-week post-op visit, with the stated timeframe extending from surgery to approximately 1 week post surgery. The registry reports one outcome measure and no posted secondary outcomes. Information about the trial's original sample-size justification, detailed statistical analysis plan, recruitment flow, and analysis populations is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

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 Incidence of Urinary Track Infection (UTI), measured over From surgery to one week post-op visit, approximately 1 week post surgery.

The primary endpoint is the incidence of urinary tract infection, recorded as the count of participants diagnosed with UTI at the one-week post-op visit. Its timeframe runs from surgery to that visit, approximately 1 week post surgery. In this context, incidence means whether a participant was counted as having the event during the specified assessment period; the result is presented as event counts and a comparison of the groups.

A binary endpoint is useful when the clinical question concerns whether an event occurred, rather than how often it occurred or how long it took to occur. In general, reducing the outcome to an event count makes the group comparison straightforward, but it also omits information about symptom intensity, recurrence, and timing within the follow-up period. Those features are not included in the posted primary result.

The registry description says UTIs will be diagnosed at the one-week post-op visit. It does not report the diagnostic criteria, who made the diagnosis, whether laboratory confirmation was required, or how an unavailable visit or incomplete outcome assessment was handled. The primary endpoint therefore communicates the recorded event counts and timing, while the record leaves important operational details about event ascertainment unspecified.

7. Results Posted in the Registry

• Methenamine Hippurate With Cranberry: 66.7% (62/93) versus 79.8% (71/89) on control; risk difference -13.1 percentage points (95% CI -25.8 to -0.4), risk ratio 0.84 (0.70–1.00); unadjusted two-proportion z-test p = 0.046.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each participant is counted according to whether a UTI was recorded during the specified assessment period. In general, a binary endpoint can be summarized by the number of events and the number assessed in each group. The posted counts are 62 of 93 in the methenamine hippurate with cranberry group and 71 of 89 in the placebo with cranberry group. The corresponding posted proportions are 0.667 and 0.798, respectively. These quantities describe the observed endpoint in the reported denominators; the registry record does not explain missing assessments or exclusions that may account for the denominators.

What does the risk difference express?

The risk difference subtracts the event proportion in the comparator group from the event proportion in the intervention group. It is an absolute measure: it describes the distance between the group proportions on the probability scale. The posted estimate is -0.131. Its negative sign indicates that the observed proportion was lower in the methenamine-plus-cranberry group than in the placebo-plus-cranberry group. The estimate is not a relative change and should not be read as an odds ratio or a risk ratio.

In general, an absolute measure is useful for understanding the observed separation between groups in the endpoint's own scale. Its size depends on the event proportions in the groups being compared. This trial's result is conditional on its population, endpoint definition, follow-up period, and recorded assessment. The registry does not report additional adjusted estimates that would account for other measured characteristics.

What do the risk ratio and odds ratio add?

The posted risk ratio is 0.836, with interval limits of 0.700 and 0.998. A risk ratio compares the event probability in one group with the event probability in the comparator. A value at the no-difference point means equal probabilities; values below that point indicate a lower probability in the intervention group for the direction used in this comparison.

The posted odds ratio is 0.507, with interval limits of 0.259 and 0.994. Odds are calculated from the event probability relative to the probability of no event, so an odds ratio compares odds rather than probabilities. In general, the odds ratio can look farther from its no-association value than the risk ratio, particularly when events are common. Readers should therefore focus on the measure that matches the question and avoid treating these scales as equivalent. The registry does not identify the risk ratio or odds ratio as the primary estimand; the primary comparison is presented as a risk difference.

How should the confidence interval be read?

The risk-difference confidence interval runs from -0.258 to -0.004. In general, a confidence interval represents uncertainty in an estimate under the statistical model and procedure used. It is not a range containing all individual outcomes, nor does it establish that the true effect must be at a particular point within the interval. A narrow interval indicates greater precision than a wide interval on the same scale; the interval spans values that range from a more pronounced negative difference to one close to no difference.

The confidence intervals for the risk ratio and odds ratio are on their respective ratio scales. For those measures, the no-association value is 1, whereas for a risk difference it is 0. This distinction matters when interpreting whether an interval includes the value representing no group difference. The posted intervals have upper limits near, but below, their respective no-association values.

What does the p-value describe?

The unadjusted p-value is 0.046. In general, a p-value describes how compatible the observed data are with a specified null model, assuming that model and the test's conditions apply. It is not the probability that the null hypothesis is true, nor is it a measure of the clinical importance of the observed difference. The registry record does not report the full test specification, whether the p-value is the result of a prespecified primary analysis, or whether it was adjusted for multiple comparisons. It should be read as the unadjusted p-value posted for this comparison.

Random assignment can support a causal comparison when the trial is conducted and analyzed as intended, but interpretation also depends on implementation and follow-up. The record does not report details of allocation concealment, protocol deviations, adherence, missing data, or the analysis population. Those omissions limit assessment of how fully the posted comparison preserves the benefits of randomization. No calculation beyond the posted estimates is needed to make that distinction: statistical measures describe the recorded group comparison, while design and reporting details shape how confidently it can be interpreted.

10. Confidence Intervals and Precision

The risk-difference estimate is -0.131, with a confidence interval from -0.258 to -0.004. This interval shows meaningful uncertainty about the magnitude of the group difference: its lower limit is more negative than the point estimate, while its upper limit is close to zero. The interval does not include zero as reported, but the proximity of its upper limit to zero signals that the data are compatible with an estimate near no difference under the analysis used.

In general, a confidence interval is a measure of statistical precision, not a guarantee about where the true effect lies. Its interpretation depends on the model and procedure used to construct it. The registry record does not report the detailed method for the interval, whether any adjustment was made, or whether the reported analysis accounted for missing outcomes. The interval should therefore be read together with the reporting limitations rather than as a complete description of uncertainty.

The risk-ratio interval, 0.700 to 0.998, and the odds-ratio interval, 0.259 to 0.994, also place their upper limits close to the no-association value of 1. The different widths and numerical scales cannot be directly compared as if they measured uncertainty in identical units. Each interval describes its own effect measure.

The unadjusted p-value is 0.046. It is close to 0.05, and the confidence interval's upper limit for the risk difference is close to zero. Together, these summaries call for attention to the estimate and its uncertainty, rather than a binary reading based only on whether a threshold is crossed. The short follow-up and the absence of reported details about outcome completeness further limit the precision with which the result can be generalized beyond the recorded assessment.

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 planning figures are participants per arm, not total events. The calculation uses the observed effect as a reference and illustrates the size of a future study under stated assumptions; it is not observed power. The trial's own original design assumptions, including any original target and justification, are not reported in the registry record.

The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. These are planning assumptions for the illustration, not a description of the trial's own design process.

For planning for 100% of the observed effect, the figures are 178 participants per arm for 80% power and 238 participants per arm for 90% power. For planning for 75% of the observed effect, the figures are 305 participants per arm for 80% power and 408 participants per arm for 90% power. For planning for 50% of the observed effect, the figures are 656 participants per arm for 80% power and 878 participants per arm for 90% power.

In plain language, the 80% power column gives the estimated participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and the assumptions hold. The 90% power column gives the corresponding estimate for a design targeting 90% power. A smaller effect is harder to distinguish from random variation, so the illustration requires more participants per arm as the targeted fraction of the observed effect becomes smaller. These are planning illustrations based on the observed result, not guarantees that a future study will detect an effect.

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 = 0.798; treatment proportion p₁ = 0.667; average p̄ = 0.732.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6262 = 1.2274.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6193 = 0.5212.
4. n = (1.2274 + 0.5212)² / (-0.1311)² = 177.9, rounded up to 178 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 <- 0.797752808988764                          # control proportion
p1 <- 0.666666666666667                          # 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(3818321)
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 = 178 (80% power), 238 (90% power)
 75% of observed effect: n per arm = 305 (80% power), 408 (90% power)
 50% of observed effect: n per arm = 656 (80% power), 878 (90% power)
power.prop.test: 177.9 
Simulated power at n = 178 per arm: 0.799 (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 outcome measure, the incidence of UTI, and reports no posted secondary outcomes. This limits the number of outcome results available for consideration, but it does not establish that no other outcomes or analyses were collected or planned. The record does not report whether multiple comparisons were planned, whether any multiplicity adjustment was used, or how the primary comparison was selected from a protocol or analysis plan. The posted p-value is unadjusted.

Missing-data handling is not reported in the registry record. The endpoint denominators are 93 in the methenamine hippurate with cranberry group and 89 in the placebo with cranberry group, while registry enrollment is 185. The record does not explain why these reported quantities differ, whether every randomized participant had an outcome assessment, or how incomplete assessments were treated. It also does not state whether any participants were excluded from the analysis after randomization.

The analysis population is not reported in the registry record. It is therefore not possible to establish from the posted information whether the comparison included all randomized participants, only participants who completed follow-up, or another defined group. The record also does not describe protocol deviations, crossover, adherence, or handling of participants who did not follow the assigned regimen.

These omissions matter because a randomized comparison is most readily interpreted when the analysis population and handling of missing outcomes are clear. In general, missing outcome data can affect the estimated group proportions, particularly if the chance of having an outcome recorded differs by group or by outcome status. No pattern of missingness can be inferred from the registry record, so no direction or size of any such effect can be stated. The analysis methods, interim analyses, and detailed statistical plan are not reported in the registry record.

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 0% reporting threshold.

The posted serious adverse event figures report zero affected participants in the methenamine hippurate with cranberry group and zero in the placebo with cranberry group. The reported numbers at risk are 93 and 89, respectively. The other adverse event figures also report zero affected participants in each group, with the same respective numbers at risk. The deaths field is zero for each group, and no serious adverse event terms are listed.

These figures describe what was recorded in the registry results; they do not establish that no adverse events of any kind occurred. The record does not describe the safety collection period, definitions used for serious or other adverse events, how events were solicited, or whether all participants had complete safety follow-up. The figures also do not provide detail on symptoms or events outside the categories reported.

In general, a zero count in a posted category means that no affected participants were entered for that category in the reported results. It is not evidence of zero risk. The short outcome timeframe for the primary endpoint should not be assumed to define the safety follow-up period, because that period is not reported in the registry record. The safety counts should be interpreted as limited registry reporting, rather than as a comprehensive characterization of safety.

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

The posted primary comparison records fewer participants with UTI in the methenamine hippurate with cranberry group than in the placebo with cranberry group over the stated period from surgery to the approximately one-week post-op visit. The risk-difference estimate is -0.131, and its confidence interval runs from -0.258 to -0.004. The unadjusted p-value is 0.046. These statistics describe the direction and uncertainty of the reported comparison; they do not by themselves establish a broad or lasting effect.

The contrast is specifically between methenamine hippurate plus cranberry and placebo plus cranberry. It cannot be interpreted as a comparison of cranberry supplementation against no supplementation, because cranberry was included in both groups. Nor does the comparison directly answer whether either regimen would have the same result in patients without postoperative urinary retention requiring a Foley catheter or in a different surgical setting.

The endpoint was UTI diagnosis at the one-week post-op visit. It does not report time to infection, infection severity, recurrence, or outcomes after that visit. The registry does not report diagnostic criteria, details of missing assessments, the analysis population, or adherence to the medication schedule. These limits affect how far the result can be carried beyond the recorded endpoint and group comparison.

In general, a randomized trial can provide evidence about a treatment contrast when allocation, follow-up, and analysis are well implemented. The registry identifies randomized allocation and masking, but does not provide enough detail to assess all those aspects. The result should therefore be read as a short-term, registry-reported comparison with statistical uncertainty and incomplete reporting about analysis conduct. It is not a statement that treatment works or does not work, and it does not substitute for broader evidence or clinical judgment.

16. Why This Trial Matters Statistically

This trial raises a useful statistical question about an added intervention within a shared-care context. Both arms received cranberry supplementation, while the randomized contrast was methenamine hippurate versus placebo. That structure focuses the primary comparison on the added tablet assignment rather than on cranberry itself. Interpreting the result correctly depends on keeping that contrast in view.

The endpoint is binary and assessed at a defined short-term visit. The risk difference makes the observed group separation interpretable on an absolute probability scale, while risk ratio and odds ratio express it on relative scales. Their confidence intervals all approach the value representing no group difference. Reading the estimate, interval, and p-value together is more informative than treating the unadjusted p-value alone as a complete account of evidence.

The result also illustrates why statistical significance and precision are not the same question. The unadjusted p-value is 0.046, while the risk-difference interval extends from -0.258 to -0.004. The interval communicates a range of estimates compatible with the reported method, including values close to no difference. In general, uncertainty about magnitude remains important even when an interval lies to one side of its null value.

Finally, the posted record makes clear that planning calculations based on an observed effect are not the same as the trial's original sample-size justification. The planning figures vary with the effect targeted and the desired power. The original design assumptions are not reported, and the posted result does not include secondary outcomes or analysis-population details. These reporting features shape what can be learned from the numerical comparison and what remains uncertain.

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 endpoint's operational definition is limited in the registry record. UTIs were to be diagnosed at the one-week post-op visit, but diagnostic criteria, use of laboratory confirmation, assessor procedures, and adjudication are not reported. The record also does not say whether an unavailable visit counted as a missing outcome or how that circumstance was handled.

Follow-up for the primary outcome was short, extending from surgery to approximately 1 week post surgery. No later UTI outcomes, recurrence data, or longer-term safety follow-up are described in the posted record. The findings therefore pertain to the stated early postoperative assessment, not to outcomes over an unspecified later period.

The population is described as patients with transient postoperative urinary retention requiring a Foley catheter after pelvic reconstructive surgery. The record does not provide further eligibility detail, baseline characteristics, or subgroup results. The generalizability of the comparison to other patient groups or care settings cannot be assessed from the information reported.

Although the trial is identified as randomized and quadruple-masked, allocation-sequence generation, concealment, and the identities of masked roles are not reported. The record does not provide adherence, protocol deviation, crossover, or analysis-population details. Missing-data methods and the original statistical analysis plan are also not reported. Registry enrollment is 185, while the posted outcome denominators are 93 and 89; the reason for the difference is not explained. These gaps limit assessment of how the reported analysis relates to all enrolled or randomized participants.

The posted primary comparison is unadjusted, and no secondary outcomes are posted. The registry does not report whether other comparisons were planned or whether multiplicity was considered. The planning sample-size illustration is based on the observed effect, and the trial's own original sample-size assumptions are not reported. These points should temper interpretation of the estimate without implying a particular direction of bias.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Urinary Track Infection Prevention After Urogynecological Surgery — NCT03818321.
• Registry record last updated 2022-11-14; status last verified 2022-10.
• Results first posted 2022-11-14.
• 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

NCT03818321 is a completed randomized phase 2 parallel-group trial sponsored by TriHealth Inc. The registry reports quadruple masking and describes a comparison of methenamine hippurate with cranberry against placebo with cranberry after urogynecological surgery. Enrollment is listed as 185, with study start on 2019-06-17 and primary completion on 2021-07-01.

The primary outcome was incidence of UTI, counted as participants diagnosed at the post-op visit approximately 1 week after surgery. The posted result reports 62 of 93 participants with UTI in the methenamine group and 71 of 89 in the placebo group. The risk difference is -0.131, with a confidence interval from -0.258 to -0.004 and an unadjusted p-value of 0.046.

No secondary outcomes are posted. Serious adverse events, other adverse events, and deaths are recorded as zero in each group. The registry record does not report the original sample-size justification, detailed missing-data handling, analysis population, or full statistical plan.