Acoustic Enhancer Research on Laser Lithotripsy (AEROLITH): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acoustic Enhancer Research on Laser Lithotripsy (AEROLITH) (NCT04563039), a randomized na study. The primary outcome is Number of Participants With Absence of or Have Residual Fragments Measuring Less </= to 2 mm.

2. Clinical Question

3. Trial Design

AEROLITH, registered as NCT04563039, is described as a pivotal study evaluating Acoustic Enhancer use with ureteroscopic laser lithotripsy in the treatment of urinary stones. The registry lists a randomized, double-masked, parallel design. Randomization is intended to support a fair comparison by assigning participants to treatment groups through chance, while masking is intended to limit the influence of knowledge about assigned treatment on study conduct or assessment. The registry record does not report who was masked or how masking was maintained.

The two interventions were ureteroscopic laser lithotripsy with Acoustic Enhancer and standard ureteroscopic laser lithotripsy. The primary outcome count is reported for 100 participants in the enhancer arm and 90 in the standard arm. These arm-specific outcome denominators differ from the registry’s enrollment entry of 196; the record does not explain the relationship between enrollment and the denominators used for this outcome. The analysis population, reasons for any differences, and handling of participants without a recorded CT outcome are not reported in the registry record.

The study start date is 2021-05-21, and primary completion is recorded as 2023-07-11. Its status is COMPLETED. The phase is listed as NA. The registry names Avvio Medical as sponsor. Although the design is randomized and double-masked, details such as allocation concealment, randomization method, planned strata, follow-up procedures, and the statistical analysis plan are not reported in the registry record. Those omissions limit what can be said about how the trial was implemented beyond the design labels and outcome information posted.

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

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 Absence of or Have Residual Fragments Measuring Less </= to 2 mm, measured over At 30 days post index procedure.

The primary endpoint counts participants who, at 30 days after the index procedure, either had no stones on the treatment side or had residual fragments measuring less than or equal to 2 mm. CT imaging was used to assess this outcome. The registry combines complete absence of stones and small residual fragments into one binary result: a participant either meets the stated criterion or does not.

This kind of endpoint provides a direct, clinically interpretable description of the imaging result at a specified follow-up time. A threshold also turns a range of possible fragment sizes into a consistent classification for comparison between randomized groups. The endpoint does not describe the full distribution of residual fragment sizes, the number or location of fragments below the threshold, or changes between the procedure and the follow-up scan. Those details are not reported in the registry record.

The reported counts are 41 participants meeting the criterion in the enhancer arm and 42 in the standard-treatment arm. The associated denominators are 100 and 90, respectively. The endpoint is therefore a participant-level count, not a measure of average stone size or a time-to-event outcome. Its interpretation depends on how CT assessments were conducted and how missing or unevaluable scans were handled; those procedures are not reported in the registry record.

7. Results Posted in the Registry

• Ureteroscopic Laser Lithotripsy With Acoustic Enhancer: 41.0% (41/100) versus 46.7% (42/90) on control; risk difference -5.7 percentage points (95% CI -19.8 to 8.4), risk ratio 0.88 (0.64–1.21); unadjusted two-proportion z-test p = 0.432.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each participant is classified according to whether the CT assessment at 30 days meets the stated stone-fragment criterion. For a binary outcome, a group’s observed proportion is the number meeting the criterion relative to the number assessed in that group. The registry posts 41 of 100 for the enhancer arm and 42 of 90 for the standard arm. The comparison below uses these summary counts and does not adjust for other variables.

What does a risk difference express?

A risk difference subtracts one group’s event proportion from the other group’s event proportion. Here the event is meeting the endpoint criterion, not experiencing an adverse event. A value of zero would represent equal observed proportions under the comparison’s direction. Negative or positive values indicate which group has the lower or higher observed proportion, respectively. The reported risk difference is -0.057. This is an unadjusted recalculation from the posted summary statistics, not a sponsor-reported analysis. The registry record does not report a different adjusted estimate.

How do risk ratios and odds ratios differ?

A risk ratio compares the event proportions as a ratio, while an odds ratio compares the odds of meeting the endpoint. Both are alternative scales for describing the same binary comparison, but their numerical values are not interchangeable. The posted risk ratio is 0.879, with a confidence interval from 0.636 to 1.213. The posted odds ratio is 0.794, with a confidence interval from 0.447 to 1.411. Because the intervals include 1, they include the null value for those ratio measures. The registry record does not report an adjusted model for either measure.

What does the p-value describe?

The unadjusted p-value is 0.432. In general, a p-value is calculated under a null hypothesis and a statistical model, and describes how unusual results at least as incompatible with that null would be if the model and null were correct. It does not give the probability that the null is true, the probability that the result is due to chance, or the size of an effect. The registry record does not report the test used, its detailed assumptions, or a prespecified decision rule. The p-value should therefore be understood as a descriptive unadjusted result rather than a complete account of the trial’s analysis plan.

Why do the confidence intervals matter?

A confidence interval presents a range of effect estimates compatible with the observed data under the method’s assumptions. It communicates uncertainty that is not visible in a point estimate alone. The risk-difference interval runs from -0.198 to 0.085. Since it includes zero and values on both sides of zero, it leaves substantial uncertainty about the direction and size of the group difference. The ratio intervals similarly include 1, their null value. A confidence interval is not a guarantee that the true effect lies within its particular limits, and it does not account for biases or design limitations that the statistical method does not capture.

What does randomized allocation contribute?

Randomization can reduce systematic differences between groups at assignment, on average, and supports a causal comparison when the trial is properly conducted and analyzed. It does not ensure that groups are identical in every characteristic, particularly in a particular study. The registry lists random allocation but does not report its sequence-generation method, allocation concealment, or baseline characteristics. The record also does not state whether the posted comparison follows an intention-to-treat approach or another analysis population. These details matter when assessing whether the summary counts preserve the benefits of randomization.

What analysis details remain unknown?

The registry lists zero posted analyses and does not provide a statistical analysis plan, secondary outcome results, missing-data methods, covariate adjustment, interim analysis information, or an explanation of the outcome denominators. These items are not reported in the registry record. The comparison estimates are simple unadjusted recalculations from the posted summary counts. They should not be confused with an adjusted sponsor analysis or a reconstruction of an unreported analysis plan. No additional assumptions about the trial’s inferential procedures can be established from the posted information.

10. Confidence Intervals and Precision

The risk-difference estimate is -0.057, and its 95% confidence interval extends from -0.198 to 0.085. The interval crosses zero, the value corresponding to no difference on the risk-difference scale. It therefore does not isolate a single direction of effect: the data are compatible with a lower endpoint proportion in the enhancer arm, little or no difference, or a higher proportion. The width of the interval indicates that the point estimate is not highly precise.

The ratio estimates tell a similar uncertainty story. The risk ratio is 0.879, with a 95% confidence interval from 0.636 to 1.213. The odds ratio is 0.794, with a 95% confidence interval from 0.447 to 1.411. For these ratio scales, 1 represents the null comparison, and each interval spans that value. The different point estimates arise because the measures use different scales; their intervals should not be read as independent findings.

Confidence intervals reflect sampling uncertainty under the methods used to construct them. They do not automatically account for missing outcome data, departures from the intended design, measurement differences, or selective reporting. The registry record does not report enough analysis detail to assess those issues or to verify the interval construction beyond the posted estimates. In practical terms, the results are too uncertain to support a sharply defined estimate of the comparative difference from the registry counts alone.

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 illustrative calculations based on the observed effect, not the trial’s own design assumptions. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These assumptions are known for the planning illustration; the original trial’s sample-size assumptions and justification are not reported in the registry record.

The entries are participants per arm for 80% power and participants per arm for 90% power. The 80% column describes the number of participants per group that the calculation estimates would be needed to have an 80% chance of detecting the selected effect under the stated assumptions. The 90% column expresses the corresponding planning target for a 90% chance. Neither column reports how many participants were actually analyzed, and neither is an estimate of the probability that the trial’s result is correct.

For planning at 100% of the observed effect, the figures are 1,203 participants per arm for 80% power and 1,610 for 90% power. At 75% of the observed effect, they are 2,146 and 2,872. At 50% of the observed effect, they are 4,844 and 6,484. A smaller effect is harder to distinguish from random variation, so the planning calculation requires more participants as the target effect becomes smaller. These are planning illustrations, not observed power; observed power is not a useful substitute for interpreting the estimate and its confidence interval.

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 = 0.467; treatment proportion p₁ = 0.410; average p̄ = 0.438.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7017 = 1.3753.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7006 = 0.5896.
4. n = (1.3753 + 0.5896)² / (-0.0567)² = 1,202.4, rounded up to 1,203 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 <- 0.466666666666667                          # control proportion
p1 <- 0.41                          # 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(4563039)
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 = 1,203 (80% power), 1,610 (90% power)
 75% of observed effect: n per arm = 2,146 (80% power), 2,872 (90% power)
 50% of observed effect: n per arm = 4,844 (80% power), 6,484 (90% power)
power.prop.test: 1202.4 
Simulated power at n = 1,203 per arm: 0.803 (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 posts one primary outcome measure and no secondary outcome measures. It lists zero analyses. The record does not report whether other outcomes were collected but not posted, whether there were additional planned comparisons, or whether any multiplicity adjustment was specified. Without that information, the extent to which the reported endpoint was selected from a wider set of outcomes or analyses cannot be assessed. No correction for multiple testing should be assumed.

The registry record does not report how participants with missing CT imaging, unevaluable scans, withdrawal, or other incomplete follow-up were handled. It also does not state whether the primary comparison used an intention-to-treat population, a per-protocol population, or another analysis set. The posted denominators for the primary outcome are 100 and 90, while registry enrollment is 196; the record does not explain that relationship. It would be inappropriate to infer why the numbers differ or to assume that missing results were handled in a particular way.

Details about baseline balance, adjustment for prognostic variables, interim analyses, stopping rules, and the statistical analysis plan are not reported in the registry record. Their absence does not prove that such methods were or were not used in the conduct of the trial; it means they cannot be evaluated from the posted record. The available comparative estimate is an unadjusted recalculation from the summary counts, not a substitute for a complete prespecified analysis. These gaps constrain interpretation of the p-value and confidence intervals, especially if the analysis population or outcome reporting differs from the plan.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection: urinary tract (3.9%), psychological (1.1%), pain (1.1%), pulmonary / respiratory (1.1%), infection: genital urinary (1.0%).

The registry reports serious adverse events for 103 participants at risk in the enhancer group and 93 at risk in the standard-treatment group. Serious adverse events affected 4 participants in the enhancer group and 5 in the standard-treatment group. Deaths are reported as 0 in each group. The record also reports other adverse events affecting 36 participants in the enhancer group and 43 in the standard-treatment group, with 103 and 93 participants at risk, respectively.

These are group-level counts, not a complete description of event timing, duration, severity, relatedness, or recurrence. The registry does not report detailed participant-level safety histories or the criteria used to classify events. The listed serious-event terms include Infection: Urinary Tract at 3.9%, Psychological at 1.1%, Pain at 1.1%, Pulmonary / respiratory at 1.1%, Infection: Genital urinary at 1.0%, and Steinstrasse at 1.0%. The percentages are recorded term summaries and should not be treated as a full account of all events or as direct comparative risks without further detail. Counts alone do not establish a causal relationship between a procedure and an event.

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

The posted primary endpoint describes the proportion of participants with no stones or only residual fragments measuring 2 mm or less on the treatment side at 30 days, as assessed by CT imaging. The observed counts are 41 of 100 in the Acoustic Enhancer arm and 42 of 90 in the standard-treatment arm. The unadjusted risk difference is -0.057, with a confidence interval that includes zero and extends in both directions. The result therefore leaves uncertainty about both the direction and magnitude of the comparative difference.

This finding is not evidence that the two procedures are equivalent. Equivalence requires a defined margin and an analysis designed to test whether the difference falls within that margin; such a margin and analysis are not reported in the registry record. Nor does the result establish that either approach is better. A p-value of 0.432 does not prove the absence of an effect, and the interval’s range makes clear that the estimate is not precise enough to settle the comparison.

The endpoint is specific to an imaging assessment at 30 days and does not describe every aspect of the treatment experience or later outcomes. The registry record does not report secondary results, missing-data handling, detailed analysis populations, or a sponsor-reported comparative analysis. The posted safety counts provide a separate, limited summary and do not establish whether events were caused by either intervention. Overall, the registry findings should be read as an uncertain comparison of the specified endpoint and as a limited account of reported safety, not as a comprehensive conclusion about all outcomes or clinical use.

16. Why This Trial Matters Statistically

This trial raises familiar statistical challenges in comparing two randomized groups on a binary endpoint. The outcome is easy to state—whether the CT assessment meets a defined residual-fragment threshold—but the interpretation depends on more than which group has the larger observed count. The denominators differ, and the comparison must account for group size rather than compare counts in isolation. The registry’s risk difference and ratio estimates provide alternative ways to express that comparison.

Precision is central. The risk-difference estimate is -0.057, but its confidence interval spans zero and includes estimates in either direction. The ratio intervals also include their respective null value. This makes it important to resist interpreting the point estimate as a settled result. A non-small p-value does not show that groups are identical; it signals that the data do not provide a precise separation under the unadjusted comparison.

The record also illustrates why reporting methods matters. Randomized, double-masked, parallel allocation gives useful design context, but it does not reveal how allocation was implemented, who was masked, how missing scans were treated, or which participants were included in analysis. Those details affect the strength and scope of conclusions that can be drawn. The lack of posted secondary outcomes and analysis detail further limits the ability to assess multiplicity or compare planned and reported results.

Finally, planning calculations based on the observed effect can help readers understand how much information would be needed to target effects of different sizes under stated assumptions. They do not reconstruct the trial’s original design rationale or turn the observed result into a probability of success. Distinguishing planned sample size, observed counts, effect estimates, and uncertainty is essential to reading this registry record responsibly.

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.

Several trial-specific limitations follow from what is and is not reported. The endpoint is assessed at 30 days after the index procedure, so the posted primary result addresses that time point rather than longer-term outcomes. It uses a CT-based threshold that combines no visible stones with residual fragments measuring 2 mm or less; the registry does not post the full distribution of fragment sizes or additional imaging outcomes.

The outcome denominators are 100 for the enhancer arm and 90 for the standard arm, while the registry enrollment entry is 196. The record does not explain the difference, state how many participants lacked an evaluable CT result, or describe how incomplete follow-up was handled. The analysis population is not reported. These omissions mean that the potential influence of missing outcome data cannot be assessed from the registry summary.

Although the design is listed as randomized and double-masked, the method of randomization, allocation concealment, identities of masked parties, and baseline group characteristics are not reported. The record also lacks a posted statistical analysis plan, sponsor-reported analysis results, secondary outcomes, multiplicity procedures, and information on interim analyses. The comparative estimates are unadjusted recalculations from summary counts, so they do not address possible adjustment strategies or other planned analyses. These limitations narrow the interpretation to the information recorded for the primary endpoint and reported adverse-event counts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Acoustic Enhancer Research on Laser Lithotripsy (AEROLITH) — NCT04563039.
• Registry record last updated 2025-04-24; status last verified 2025-04.
• Results first posted 2025-04-24.
• 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

NCT04563039, titled AEROLITH, evaluates ureteroscopic laser lithotripsy with Acoustic Enhancer compared with standard ureteroscopic laser lithotripsy for urinary stones. The registry lists a randomized, double-masked, parallel design and a COMPLETED status. The study start date is 2021-05-21, and primary completion is recorded as 2023-07-11.

The primary endpoint is the number of participants with no stones or residual fragments measuring 2 mm or less on the treatment side at 30 days, assessed by CT imaging. The registry posts 41 of 100 in the enhancer arm and 42 of 90 in the standard arm. The unadjusted risk difference is -0.057, with a 95% confidence interval from -0.198 to 0.085 and an unadjusted p-value of 0.432. The interval includes zero, leaving uncertainty about the direction and size of the difference. Serious adverse events affected 4 participants in the enhancer group and 5 in the standard group; deaths are reported as 0 in both groups. The registry does not report detailed analysis methods or secondary outcome results.