Feasibility and Efficacy of Coronary Sinus Narrowing in Patients With Coronary Microvascular Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility and Efficacy of Coronary Sinus Narrowing in Patients With Coronary Microvascular Dysfunction (NCT04523168), a na na study. The primary outcome is Change in Coronary Flow Reserve (CFR).

2. Clinical Question

The study concerns symptomatic patients with coronary microvascular dysfunction and chronic refractory angina. It evaluates implantation of the Neovasc Reducer™ System, a device intended to be studied for its relationship to microvascular function, symptoms, and quality of life. The registry record identifies coronary flow reserve (CFR) as the primary outcome and lists the Seattle Angina Questionnaire and change in Canadian Cardiovascular Society Angina Class among the secondary outcomes.

Because the study has no recorded comparison group, its primary question is about change over time within the enrolled group, rather than a contrast between people assigned to different treatments. That distinction matters: a before-and-after change can describe what happened during the study, but by itself it cannot separate the intervention’s contribution from other influences on measurements or symptoms.

The listed secondary outcomes address patient-reported angina-related health status and angina class. The registry record does not provide their numerical results, the exact assessment schedule for those outcomes, or details of the instruments’ scoring and analysis. The central clinical question is therefore identifiable from the record, but the magnitude and precision of any measured changes are not reported in the registry record.

3. Trial Design

The registry lists this as a completed, single-group study with enrollment of 30. Its title describes it as a Phase II study, while the registry phase entry is NA. Allocation is recorded as NA and masking as NONE. The record does not describe a randomized assignment or a masked assessment process. The arm description is Chronic Refractory Angina, and describes device implantation in the cardiac catheterization laboratory.

The registry lists the study start as 2021-06-28 and primary completion as 2023-07-28. Its status is COMPLETED. Those administrative details describe the trial record and do not, on their own, indicate whether the primary outcome favored a particular direction or whether the study met a prespecified target. Numerical primary outcome results are not reported in the registry record.

For a single-group design, the key analysis is ordinarily a description of measurements over time in the enrolled group. This differs from a randomized comparison, where the treatment groups can provide a contemporaneous basis for estimating a between-group contrast. Since this record does not list a separate control group, any observed change in CFR would need to be interpreted as change during follow-up rather than as a randomized estimate of the device’s effect.

The posted study purpose is to evaluate the device in relation to microvascular function, symptoms, and quality of life. The primary outcome is change in CFR from baseline to 120 days. The registry also lists the Seattle Angina Questionnaire and change in Canadian Cardiovascular Society Angina Class as secondary outcomes. The precise procedures for measuring these secondary outcomes, the details of follow-up, and the analysis plan are not reported in the registry record.

The sample-size assumptions describe an illustrative calculation based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These assumptions describe a planning illustration, not the recorded single-group design. The registry record does not report a sample-size justification from the trial protocol, and a planning calculation based on an observed effect is not observed power.

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 Change in Coronary Flow Reserve (CFR), measured over Baseline, 120 days.

The primary endpoint is change in coronary flow reserve (CFR), expressed as a ratio and summarized using a mean and standard deviation. The registry describes CFR as the ratio of hyperemic or maximal flow down a coronary vessel to resting coronary blood flow. The listed timeframe is baseline and 120 days.

CFR is used as a measure of coronary microvascular function. A change endpoint compares a follow-up measurement with a baseline measurement, so its interpretation depends on how the measurements were obtained and how the change was calculated. The record identifies the endpoint and time points, but does not provide the observed baseline or follow-up means, the mean change, its standard deviation, or an interval estimate. Those numerical results are not reported in the registry record.

In general, a mean summarizes the central value of a continuous measurement, while a standard deviation describes the spread of individual values around that mean. Neither statistic alone describes how precisely the mean change has been estimated; an uncertainty interval would help convey that precision. The registry record does not report such an interval for CFR.

The endpoint can describe a physiological measurement, but it does not by itself establish how patients felt or functioned. The registry lists symptom and angina-class measures separately as secondary outcomes, reflecting different kinds of information. Their results and their relationship to CFR change are not reported in the registry record. Accordingly, the endpoint definition is clear, but the magnitude and clinical interpretation of the observed change cannot be assessed from the posted numerical information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as continuous and reports it as a mean with standard deviation. This describes the intended summary of CFR change, but it does not specify which statistical test or model was used. The analysis method, adjustments, and handling of repeated measurements are not reported in the registry record.

What does a mean change describe?

In general, a change score is formed by comparing a follow-up measurement with a baseline measurement for an individual, and then summarizing those changes across participants. A mean change describes the average direction and size of those individual changes. The exact calculation convention, including the order of subtraction, is not stated in the registry record, so the sign of a result could not be interpreted without the analysis definition. No numerical mean change is reported.

A standard deviation describes how much individual values vary around the mean. It is not the same as the uncertainty in the estimated mean. A confidence interval is one way to express uncertainty around an estimate: it gives a range of values compatible with the data and the method used to calculate the interval. The registry record does not report a confidence interval for the primary endpoint, so the precision of the estimate cannot be assessed.

Why does the single-group structure matter?

In general, a single-group before-and-after analysis can describe within-group change, but it does not directly estimate a contrast against a concurrent control group. A change over time may reflect the intervention, other changes during follow-up, variation in the measurement, or a combination of influences. Random assignment to a comparator can help address some competing explanations by making the groups comparable on average, but no randomized comparator is recorded for this study. This is a limitation of the design for causal interpretation, not evidence that any particular alternative explanation occurred.

Repeated measurements from the same participant are related rather than independent. In general, an analysis of change should account for that relationship when estimating uncertainty. The registry identifies baseline and 120 days as time points, but does not report whether the analysis used paired changes, a repeated-measures model, an adjusted follow-up model, or another approach. It also does not describe covariates or missing-measurement procedures.

What can the adverse-event summaries establish?

In general, adverse-event counts describe events recorded under the trial’s definitions and observation process. A count of affected participants is not necessarily equivalent to a count of all event episodes, and an event’s occurrence after an intervention does not by itself establish that the intervention caused it. The registry lists serious and other adverse-event counts, but does not report the event definitions, exposure duration, severity grading rules, or causal attribution procedures. Those details are not reported in the registry record.

The serious-term listing gives wire related perforations with 6.7%. That percentage is a reported registry value; it should not be treated as a comparative risk estimate. No control-group event rate is recorded, and the record does not provide a comparison with another device or usual care. The available adverse-event information therefore supports a limited descriptive reading rather than a comparative safety conclusion.

How should the planning illustration be read?

The planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also define the effect to detect as a stated fraction of the observed effect. Those are assumptions for an illustrative planning exercise. The study itself is recorded as single-group, so the assumed equal allocation between two arms is not a description of its actual design.

In general, a sample-size calculation asks how much information a proposed design might need to detect a specified effect under stated assumptions. Its result is sensitive to the assumed effect, variability, significance threshold, allocation, and analysis model. A calculation that uses an observed effect as its basis is a planning illustration, not proof that a completed study had a particular probability of detecting an effect. It is not observed power. The registry record does not report the trial’s own sample-size justification or the numerical results of the planning illustration.

The record indicates 3 outcome measures and 2 analyses, but does not describe which analyses correspond to which measures or whether they were prespecified. It does not provide test statistics, model coefficients, adjustment methods, or analysis populations. Accordingly, the endpoint definition and broad design can be explained, while the precise statistical procedure and its assumptions cannot be reconstructed from the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Chronic Refractory Angina")
n   <- c(30)
m   <- c(3.04)
sp  <- c(1.06)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Chronic Refractory Angina  30  3.040  1.060  2.644  3.436

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary CFR outcome and secondary outcomes covering the Seattle Angina Questionnaire and change in Canadian Cardiovascular Society Angina Class. It records 3 outcome measures and 2 analyses. The registry record does not explain how the analyses map to the listed outcomes, which outcomes were included in each analysis, or whether the analysis choices were prespecified.

When a study evaluates multiple outcomes or conducts multiple statistical tests, the chance of obtaining at least one apparently noteworthy result can increase. In general, multiplicity procedures may control that risk by adjusting thresholds or by using an ordered testing strategy. The record does not report whether any multiplicity adjustment or hierarchy was used. It also does not report p-values or numerical secondary outcome results, so the implications of multiple testing cannot be evaluated from the registry entries.

Missing data can affect both the estimated change and its precision. In general, the implications depend on how many measurements are missing, why they are missing, and how the analysis handles them. The registry record does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. It also does not identify an analysis population, such as all enrolled participants or only participants with measurements at both time points.

These omissions prevent assessment of whether the analysis population matched the enrollment group, whether participants with incomplete assessments were included in any analysis, and whether the findings could be sensitive to missing measurements. The registry record does not report an intention-to-treat analysis or another defined population approach. Without those details and the outcome estimates, the robustness of any efficacy result cannot be judged.

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: wire related perforations (6.7%).

The registry reports 2 serious adverse events among 30 at risk in the Chronic Refractory Angina group. It also reports 16 other adverse events among 30 at risk and 0 deaths. Wire related perforations are listed as the leading serious term, with a reported value of 6.7%.

These figures are descriptive counts and a registry-listed percentage. They do not establish that the device caused an event, and they do not show how the event frequency compares with a control group. No comparator group is recorded. The registry record also does not describe the event definitions, observation duration for safety, severity grading, or rules for assigning causality. The listed values should therefore be interpreted within those limits.

A serious adverse event is not interchangeable with any adverse event, and the categories should not be combined or treated as equivalent. The record reports zero deaths, but that count alone does not characterize all aspects of safety. The term listing for wire related perforations does not specify whether the events were adjudicated as related to the device or procedure; that information is not reported in the registry record.

Because the study is single-group, its safety counts cannot provide a controlled estimate of excess risk. They describe events recorded in the group, rather than a difference attributable to the intervention. The small enrolled group and absent comparative data also limit how broadly the counts can be interpreted. No conclusion about comparative safety follows from these figures alone.

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

The registry record establishes that a completed single-group study evaluated implantation of the Neovasc Reducer™ System in patients described as having coronary microvascular dysfunction and chronic refractory angina. It identifies CFR change from baseline to 120 days as the primary outcome and lists symptom and angina-class measures as secondary outcomes. It also reports adverse-event counts for the recorded group.

However, the numerical primary outcome results are not reported in the registry record. The mean CFR change, its variability, and any uncertainty interval or test result are absent. The secondary outcome results are also not reported in the registry record. Consequently, the posted information does not establish whether CFR, symptoms, or angina class changed, in what direction they may have changed, or how precisely any change was estimated.

Even if a within-group change were reported, the design would not by itself establish that the intervention caused the change. The record identifies no randomized comparator. A comparison of measurements over time in one group cannot directly distinguish an intervention-related change from other influences during follow-up. This is a general limitation of interpreting single-group change, not a claim about what happened to participants.

The adverse-event counts can be read as descriptive observations, but do not support a comparative estimate of risk or establish causation. The reported counts and serious-term percentage should not be used as substitutes for the missing primary endpoint results.

In general, a treatment-effect conclusion requires an interpretable estimate, a measure of uncertainty, a suitable design for the causal question, and adequate reporting of the analysis and participant data. The registry entry does not supply those outcome and analysis details. The appropriate interpretation is therefore limited: the study’s purpose, design, endpoint, and certain event counts are recorded, while its efficacy-related result and the precision of that result are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is framed around change over time in a continuous physiological measure, while the recorded design is single-group. That combination makes it important to distinguish a description of observed change from an estimate of a causal effect. The former can characterize what was measured in the enrolled group; the latter requires a basis for comparing that experience with a credible alternative.

The endpoint definition is also useful for understanding what the study set out to measure. CFR is defined in the record as a ratio involving maximal and resting coronary blood flow, and the planned comparison is between baseline and 120 days. The endpoint is distinct from the listed symptom and angina-class outcomes. Each addresses a different aspect of the study’s purpose, so results on one measure would not automatically stand in for results on the others.

Equally important is the gap between a completed study record and a report of its outcomes. The registry identifies enrollment and study status, but does not report the primary outcome estimate or secondary outcome findings. Without those estimates and their precision, readers cannot assess the size or direction of change, nor judge how compatible the data are with different possible effects.

The planning assumptions also illustrate why calculation context matters. An equal-allocation, two-arm planning scenario is not the design recorded for this single-group study. Treating planning assumptions as trial conduct would confuse a hypothetical illustration with observed design information. Likewise, a calculation based on an observed effect is not observed power.

The statistical lesson is therefore about interpretation and reporting: design, endpoint, analysis, uncertainty, and outcome availability all shape what a result can support. The record makes the clinical question and some design features visible, but leaves the key numerical efficacy findings and analysis details unreported.

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 main trial-specific limitation for interpreting efficacy is the absence of reported numerical results for the primary endpoint. Although the registry identifies CFR change from baseline to 120 days, it does not report the observed change, the spread of the measurements, or an uncertainty estimate. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study is recorded as single-group, with allocation NA and masking NONE. There is no separate comparator recorded, limiting causal interpretation of any within-group change. Masking procedures are not described beyond the NONE entry. The record does not explain how measurements were collected or whether assessors were involved in outcome measurement.

Other details needed to assess the analysis are also absent. The statistical test or model, analysis population, handling of missing data, multiplicity approach, and prespecification of analyses are not reported in the registry record. The record indicates 3 outcome measures and 2 analyses, but does not explain their correspondence or provide the analysis specifications.

For safety, the registry gives adverse-event counts and a serious-term percentage, but does not describe event definitions, observation duration, severity grading, or attribution procedures. The lack of a comparator also means these counts cannot serve as a controlled safety contrast.

Finally, the sample-size assumptions describe an illustrative two-arm planning calculation rather than the recorded single-group design. The trial’s own sample-size justification is not reported in the registry record. Together, these omissions constrain assessment of the endpoint results, their precision, and the strength of any causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Feasibility and Efficacy of Coronary Sinus Narrowing in Patients With Coronary Microvascular Dysfunction — NCT04523168.
• Registry record last updated 2024-08-20; status last verified 2024-07.
• Results first posted 2024-08-20.
• 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

The registry lists NCT04523168 as a completed, single-group study of the Neovasc Reducer™ System in patients with coronary microvascular dysfunction and chronic refractory angina. Enrollment is 30. The title describes a Phase II study, while the phase entry is NA. Allocation is NA and masking is NONE.

The primary outcome is mean change in CFR, expressed as a ratio, from baseline to 120 days. The listed secondary outcomes are the Seattle Angina Questionnaire and change in Canadian Cardiovascular Society Angina Class. Numerical results for these outcomes are not reported in the registry record.

The record reports 2 serious adverse events among 30 at risk, 16 other adverse events among 30 at risk, and 0 deaths. Wire related perforations are listed with 6.7%. These are descriptive entries without a recorded comparator.

The primary outcome estimate, its uncertainty, analysis methods, missing-data handling, and multiplicity procedures are not reported in the registry record.