Shockwave Coronary Lithoplasty® Study (Disrupt CAD II): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Shockwave Coronary Lithoplasty® Study (Disrupt CAD II) (NCT03328949), a na na study. The primary outcome is Number of Participants With In-hospital Major Adverse Cardiac Events (MACE).

2. Clinical Question

The study is described as a prospective, multi-center, single-arm post-market study. Its stated objective was to examine the safety and performance of the coronary intravascular lithotripsy system for treating narrowed coronary arteries before stent placement. The primary endpoint focused on in-hospital MACE, a composite that includes cardiac death, myocardial infarction as defined in the registry, and target-vessel revascularization after the index procedure.

Because the registry describes no control arm, the study can report outcomes among people treated with the device but cannot directly compare those outcomes with outcomes under another treatment or with no device treatment. The primary endpoint count and its uncertainty are not reported in the registry record, so the registry information does not permit a numerical estimate of the frequency of primary-endpoint events.

3. Trial Design

This was a prospective, multi-center, single-group post-market study of the Shockwave Medical, Inc. Coronary Lithoplasty System. The registry lists the study as completed and records 120 enrolled participants. It gives a start date of 2018-05-18 and a primary completion date of 2019-03-26. The phase is listed as NA, and allocation is listed as NA. Masking is listed as none.

All enrolled participants were to receive treatment from the IVL coronary lithotripsy system before coronary stent placement. The study therefore has no randomized allocation and no parallel control arm in the registry description. The stated intervention is a device, rather than a drug regimen. The record describes the study as post-market and identifies coronary artery disease as the condition.

The primary outcome was the number of participants with in-hospital MACE from after the procedure through hospital discharge. Secondary outcomes named in the record were the number of participants with clinical success, the number with angiographic success, and the number who experienced cardiac death. The names of these outcomes appear in the record, but their observed results are not reported in the registry record.

In a single-group design, the main descriptive quantity is the frequency of outcomes among participants who received the intervention. Without a control group, outcome frequencies cannot by themselves establish how the same participants would have fared under a different approach. The lack of masking also means that the study was not described as blinded; the registry record does not report further details about outcome assessment procedures.

The registry identifies the Intent-To-Treat analysis set as the population for all analyses. It defines that set as participants whose IVL catheter insertion was attempted, with the point of enrollment marking the attempt. The record states that no imputation or adjustment for missing data was performed for the primary analysis. Further details of the study protocol, including any sample-size justification or interim analyses, 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: No imputation of or adjustments for missing data were performed for the primary analysis. The population for all analysis was the Intent-To-Treat (ITT) analysis set. ITT was defined as those subjects who had insertion of the IVL catheter attempted, defined as the point of enrollment.

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 In-hospital Major Adverse Cardiac Events (MACE), measured over Post-procedure through hospital discharge.

The primary endpoint is the number of participants with in-hospital major adverse cardiac events, measured from after the procedure through hospital discharge. The registry defines MACE using three components: cardiac death; myocardial infarction, defined as a CK-MB level > 3 times the upper limit of lab normal, with or without a new pathologic Q wave; and target-vessel revascularization, including the target lesion, after completion of the index procedure.

A composite endpoint combines distinct clinical events into one outcome. As a general statistical point, composites can capture several kinds of clinically important events and provide a single summary measure, but interpretation depends on knowing which components occurred and how often. Components can differ in severity and frequency, so a composite count alone does not show the pattern of events behind it.

The endpoint is expressed as a count of participants, rather than as a continuous measurement. The registry specifies the analysis population and the observation window, but the primary event count and any accompanying uncertainty estimate are not reported in the registry record. Consequently, the endpoint definition is available, while the observed primary outcome cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is binary at the participant level: each participant either contributes to the count of people with the composite endpoint or does not, according to the endpoint definition and observation window. The registry presents the primary outcome as a number of participants, not as a continuous measure such as a laboratory value. The CK-MB threshold is part of the myocardial infarction definition; it does not turn the primary endpoint itself into a continuous outcome.

As a general statistical point, a binary outcome can be summarized by the number of participants with the event and the number assessed. A proportion can also describe the event frequency, but no primary event count or proportion is reported in the registry record. No new frequency can be derived without the event count. A denominator alone does not reveal how many participants experienced the event.

The primary outcome is a composite. In general, a composite endpoint collects multiple event types into one summary so that the analysis can address whether any defined component occurred. Interpretation should distinguish that combined measure from its component outcomes. A composite can conceal variation across components: one component may account for more of the events than another, and components may have different clinical meanings. The registry defines the components but does not report their separate primary-endpoint counts.

For the myocardial infarction component, the registry specifies CK-MB above three times the upper limit of lab normal, with or without a new pathologic Q wave. The target-vessel revascularization component includes revascularization at the target vessel, inclusive of the target lesion, after completion of the index procedure. Cardiac death is the third component. These definitions set the event criteria; the registry record does not report additional adjudication details or the observed count for each component.

The analysis population is described as Intent-To-Treat. In this record, that population includes participants whose IVL catheter insertion was attempted, defined at the point of enrollment. This definition is important because it identifies who is counted in the analysis set. It does not, by itself, indicate that every participant completed the procedure or had every outcome measurement available. The registry states that no imputation or adjustment for missing data was performed for the primary analysis.

As a general statistical point, missing-data handling can affect an outcome estimate if participants lack outcome information. Imputation uses a stated method to fill in missing values; adjustment can account for missingness in a specified analysis. When neither is used, the interpretation depends on the available outcome information and the way missing observations are handled in the analysis. The registry does not report the extent or pattern of missing primary outcome data, so the potential effect of missingness cannot be evaluated from this record.

A confidence interval is a statistical range intended to communicate uncertainty around an estimate under a model and assumptions. For a binary outcome, the interval is tied to the event count and the analysis approach. A narrower interval generally indicates greater precision under that approach, while a wider interval indicates more uncertainty. The primary endpoint confidence interval and method are not reported in the registry record, so its precision cannot be described numerically.

Statistical tests and confidence intervals answer different questions. A test evaluates compatibility with a specified null hypothesis under its assumptions; a confidence interval gives a range of estimates compatible with the data and method at a chosen confidence level. Neither substitutes for the observed event count, and neither can be reconstructed when the necessary outcome result is absent. The registry lists zero analyses, and no primary inferential result is reported in the registry record.

Multiplicity refers, in general, to the issue of interpreting several outcomes or tests at once. When many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of tests. This study names one primary endpoint and three secondary outcomes, but multiplicity procedures or a testing hierarchy are not reported in the registry record. The existence of named outcomes does not establish that any adjustment was or was not planned.

As a general point, over-dispersion is a concern for count data when observed variation exceeds what a simple model assumes. It can affect standard errors and uncertainty estimates for some count-based analyses. The primary endpoint is described as a count of participants with a binary event, rather than a count of repeated events per participant. The registry does not report a model for the primary outcome, so there is no basis to characterize any over-dispersion assessment in this study.

Sample-size calculations are planning tools that depend on assumptions about the effect to detect, statistical significance level, allocation, and analysis method. They are not observed results and do not establish the precision achieved in a completed study. The registry record does not report the trial's own sample-size justification or interim analyses. Any planning illustration associated with the posted material should therefore be understood as a planning exercise, not as an observed-power result or as evidence of the primary endpoint finding.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Coronary Intravascular Lithotripsy (IVL) System")
n      <- c(120)
events <- c(7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Coronary Intravascular Lithotripsy (IVL) System  120  7  5.8  2.4  11.6  2.9  11.6  2.9  11.6

11. Multiplicity, Missing Data and Analysis Populations

The registry names one primary outcome and three secondary outcomes: clinical success, angiographic success, and cardiac death. It records four outcome measures overall. A plan for controlling multiplicity, prioritizing secondary outcomes, or interpreting multiple tests is not reported in the registry record. As a general statistical point, multiplicity matters when several outcomes or hypotheses are assessed because separate tests can create multiple opportunities for a nominally unusual result. The record does not provide inferential results for these outcomes.

The registry states that no imputation of or adjustments for missing data were performed for the primary analysis. It identifies the analysis population as the Intent-To-Treat set, defined as participants whose IVL catheter insertion was attempted, with enrollment marking that point. The record does not report the number of participants with missing primary outcome information or describe the pattern of any missingness. Therefore, the effect of missing data on the primary endpoint estimate cannot be assessed from the registry record.

The registry lists zero analyses and does not report the primary event count, a confidence interval, or a statistical test. It also does not report a protocol-level sample-size justification or interim analysis plan. These details should not be inferred from the enrollment count or from the named outcome measures.

12. 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: coronary artery dissection (2.5%), angina pectoris (1.7%), arrhythmia (1.7%), acute myocardial infarction (0.8%), atrial fibrillation (0.8%).

The registry records 13 participants with serious adverse events among 120 at risk, 29 participants with other adverse events among 120 at risk, and 1 death. These are safety figures reported for the IVL system group. They are descriptive counts; the registry record does not report a control group for comparison or state that the events were caused by the device.

The listed serious adverse-event terms and their recorded percentages are coronary artery dissection, 2.5%; angina pectoris, 1.7%; arrhythmia, 1.7%; acute myocardial infarction, 0.8%; atrial fibrillation, 0.8%; and mitral valve incompetence, 0.8%. These term-specific figures should be read as entries in the registry safety record, not as a comparison with another treatment. The registry does not provide further detail about event timing, clinical course, or causal attribution.

Safety-event counts and the primary MACE endpoint are not interchangeable. The record does not state whether individual adverse events overlap with MACE events, and the total adverse-event figures cannot be used to infer the missing primary endpoint result. The circumstances or cause of the reported death are not reported in the registry record.

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

The record establishes that a prospective, multi-center, single-group post-market study of the IVL coronary lithotripsy system was completed with 120 enrolled participants. The intervention was intended to be used before coronary stent placement, and the primary endpoint was in-hospital MACE from after the procedure through hospital discharge. The endpoint definition and the study population are described, but the number of participants with the primary endpoint is not reported in the registry record.

Accordingly, the registry record does not support a numerical conclusion about the observed frequency of primary MACE. It also does not report clinical success, angiographic success, or the secondary cardiac-death result. The available safety counts can be described, but they do not replace the missing primary outcome result or demonstrate a comparison with another approach.

As a general statistical point, an outcome frequency in a single group is a description of that group under the study conditions. It does not on its own show what would have happened to those participants under a different treatment. A control group, a suitable comparison strategy, and an analysis addressing the design would be needed for a direct comparative estimate. This registry record identifies no comparator group.

The study is marked completed, but completion does not mean that every planned result or analysis is reported in the registry. The record lists zero analyses. It does not report a confidence interval for MACE, so the precision of that endpoint estimate cannot be assessed. It also does not report the study's own sample-size justification or interim analyses.

The appropriate statistical reading is therefore limited: the record describes the design, endpoint definition, analysis population, and some safety counts, but it does not report the primary efficacy or safety endpoint result. It cannot establish a treatment effect or a comparative benefit, and the absence of the primary result should not be read as evidence that no MACE events occurred.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design answers a descriptive question in a treated group rather than a comparative question. The study was a single-group post-market investigation, with all enrolled participants receiving the IVL system before stent placement. That design can characterize outcomes in the enrolled group, but it does not create a randomized counterfactual for estimating how outcomes would differ under another intervention.

The primary endpoint is a composite of cardiac death, a registry-defined myocardial infarction, and target-vessel revascularization. Composite endpoints can be useful for bringing several outcomes into one prespecified measure. As a general statistical point, however, interpretation is stronger when the total result and its component results are both available. In this registry record, the endpoint definition is listed but the primary count and component results are not reported.

The record also makes the analysis population explicit: participants with attempted IVL catheter insertion, defined at enrollment. That detail clarifies who was intended to be included in the analysis. The stated absence of imputation or adjustment for missing data is also relevant, although the extent and pattern of missing outcome information are not reported.

Finally, the registry includes adverse-event counts and named secondary outcomes, but it lists zero analyses and does not report the primary result. This illustrates why design information, outcome definitions, observed results, and uncertainty estimates all matter together. A completed study record can identify what was planned and who was studied while still leaving the central endpoint estimate unavailable.

15. 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 has no comparator group in the registry description. As a result, its single-group outcomes cannot directly estimate a difference between IVL and another treatment. Allocation is listed as NA, and masking is listed as none. The record does not describe further outcome assessment procedures, so the implications of the unmasked design cannot be evaluated in detail.

The principal limitation for interpreting the stated primary question is that the primary MACE result is not reported in the registry record. The record provides the endpoint definition and timeframe, but not the event count or a confidence interval. Secondary outcome names are listed, but their observed values are also not reported. The record lists zero analyses.

The registry states that no imputation of or adjustments for missing data were performed for the primary analysis. It does not report how many primary outcome observations were missing or describe their pattern. The analysis population is defined by attempted catheter insertion at enrollment, but the record does not provide further detail on participant-level follow-up or outcome completeness.

The primary endpoint includes several different event types, but the registry does not report component counts. The safety record lists adverse-event counts and terms, but does not report whether these overlap with MACE or provide causal attribution for the events or death. Further study details, including a sample-size justification, interim analyses, and multiplicity procedures, are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Shockwave Coronary Lithoplasty® Study (Disrupt CAD II) — NCT03328949.
• Registry record last updated 2019-11-19; status last verified 2019-11.
• Results first posted 2019-11-08.
• 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.

19. Record Summary

NCT03328949 is the completed Shockwave Coronary Lithoplasty® Study (Disrupt CAD II), a prospective, multi-center, single-arm post-market study sponsored by Shockwave Medical, Inc. It enrolled 120 participants with coronary artery disease. The intervention was the IVL Coronary Lithotripsy System, used before coronary stent placement.

The primary endpoint was the number of participants with in-hospital MACE from after the procedure through hospital discharge. The registry defines MACE as cardiac death, myocardial infarction under the stated CK-MB criterion, or target-vessel revascularization after the index procedure. The primary outcome result is not reported in the registry record.

The record identifies an Intent-To-Treat population based on attempted catheter insertion and states that no imputation or adjustment for missing data was performed for the primary analysis. It reports 13 participants with serious adverse events, 29 with other adverse events, and 1 death among the group of 120 at risk. No control group is described, and the registry lists zero analyses.