Safety and Potential Bioactivity of CLBS16 in Patients With Coronary Microvascular Dysfunction and Without Obstructive Coronary Artery Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Potential Bioactivity of CLBS16 in Patients With Coronary Microvascular Dysfunction and Without Obstructive Coronary Artery Disease (NCT03508609), a na phase 2 study. The primary outcome is Change From Baseline in Coronary Flow Reserve.

2. Clinical Question

In practical terms, the study was intended to explore safety and potential bioactivity in the specified population after treatment with CLBS16. The primary measure focuses on change in a physiologic measure, rather than a comparison between assigned treatments. Secondary outcomes listed in the record cover microvascular function assessed with intracoronary acetylcholine, peripheral arterial tonometry, angina frequency and class, the Seattle Angina Questionnaire, and SF-36 scores. Those measures indicate a range of clinical and functional questions, but their listed presence does not establish that results were reported or analyzed.

Because this was a single-group study without masking, the registry design does not supply a concurrent control for interpreting change over time. The record identifies an enrolled group of 20, but it does not report the number contributing data to the primary endpoint or the endpoint findings. Thus, the clinical question is exploratory: what safety information and potential biological signal were observed after infusion? The available record describes the question and design, but does not provide the primary outcome result needed to characterize the observed change.

3. Trial Design

This is a Phase 2, open-label, single-group study of CLBS16 in people with coronary microvascular dysfunction and without obstructive coronary artery disease. The registry lists allocation as NA and masking as NONE. Its arm is described as active treatment with autologous CD34 cells. The study is marked COMPLETED, with enrollment of 20. The listed study start is 2018-04-19, and primary completion is 2019-12-10.

The brief summary describes eligible subjects as adults currently experiencing angina and states that they receive a single intracoronary infusion of CLBS16. The intervention is classified as biological. The official title characterizes the study as open-label and exploratory, with safety and potential bioactivity as its focus. These descriptions establish the intended design and treatment exposure, but do not provide a detailed protocol or explain the rationale for the enrollment target.

With one treatment group, the study can describe outcomes among treated participants but cannot make a randomized, like-for-like comparison with an untreated or alternative-treatment group. Open-label status means masking is not part of the registered design; the record does not provide further information about how outcome measurement or assessment was conducted. General design principle: a concurrent comparison group can help distinguish treatment-associated change from changes that might occur over time for other reasons. That distinction cannot be made through a between-group contrast in this single-group record.

The primary endpoint is change from baseline in coronary flow reserve at Day 180. The registry lists seven outcome measures, including secondary measures of microvascular function, angina, and health-related scores. It lists no analyses. The record does not report a statistical analysis plan, sample-size justification, interim analyses, or the number of participants with measurements at the primary time point. Completion status indicates the study is marked completed in the registry; it does not itself indicate what the outcomes were.

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 Change From Baseline in Coronary Flow Reserve, measured over Day 180.

The primary endpoint is change from baseline in coronary flow reserve at Day 180. CFR is reported as a ratio and is described in the registry as a measure of coronary microvascular function. The endpoint therefore asks whether the recorded measure at the specified follow-up differs from its baseline value. The record identifies the summary parameter as a mean and the dispersion measure as a standard deviation, but does not report the observed mean change, standard deviation, or number of participants contributing endpoint data.

In general, a baseline-to-follow-up change measure uses each participant’s starting value as a reference for interpreting a later measurement. A mean change describes the average change in the analyzed group; it does not show how much individual participants differed from that average. A standard deviation describes variability among observed values, not the precision of the mean. A confidence interval, if reported, would convey uncertainty around an estimate, but one is not reported for this endpoint in the registry record.

CFR is used as a measure of coronary microvascular function because that is the role assigned to it in the registry description. The endpoint’s stated timeframe is Day 180. The registry record does not provide a direction of expected benefit, a threshold for a meaningful change, or the result at that time point. Without those details, the endpoint can be identified and explained, but its observed magnitude and precision cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study records outcomes in participants who receive the intervention, without a concurrent control group. It can describe the observed outcomes in that group and can compare follow-up measurements with baseline measurements. It does not create a randomized contrast between treatment options. For this study, the registry lists one active-treatment arm, open-label status, and allocation as NA. No control arm is listed.

A before-and-after comparison can be informative as a description of change. However, a change within a group is not the same quantity as a treatment effect estimated from a controlled comparison. Other influences over time and variation in measurement may contribute to observed change. This general limitation applies even when the measurement is objective; the registry record does not provide enough information to assess the particular measurement procedures used for CFR.

What do the mean and standard deviation convey?

The primary outcome is continuous and is summarized using a mean, with standard deviation as the listed dispersion measure. In general, a mean describes the average value or average change across the analyzed observations. The standard deviation describes how spread out those observations are around their mean. It is not the same as the standard error and does not, on its own, give a confidence interval for the mean.

The distinction is useful because a group average can conceal variation among individuals. A mean change may summarize the overall direction of observed change while the standard deviation conveys the degree of variation in the individual values. Neither summary alone identifies the distribution of the data or the clinical importance of a change. The registry record does not report the actual mean or standard deviation for the primary endpoint.

How should uncertainty be assessed?

In general, a confidence interval presents a range of values compatible with an estimate under the assumptions of the analysis. Its width reflects precision: a wider interval indicates greater uncertainty about the estimate than a narrower interval. A p-value addresses compatibility of data with a specified null hypothesis under a statistical model; it does not measure the size or practical importance of an effect. These concepts can complement an estimate, but neither can be applied to the primary result from this record because no result or interval is reported.

For a single-group change analysis, uncertainty depends on the observed data and the analysis method, including how paired baseline and follow-up measurements are handled. General statistical principle: repeated measurements on the same participant are related, so an analysis of change should account for that pairing rather than treat the two observations as independent. The registry record does not specify the exact primary analysis method, assumptions, or uncertainty interval.

Why can variability and over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. When a model understates variability, standard errors can be too small and confidence intervals too narrow, making results appear more precise than they are. The relevance of over-dispersion depends on the outcome and model. The primary endpoint is described as a continuous measure summarized by a mean and standard deviation, but the registry record does not report a model or diagnostics that would allow assessment of over-dispersion.

What does the sample-size illustration represent?

The registry record gives general assumptions for a planning illustration: two-sided significance level 0.05, equal allocation between two arms, normal approximation, and an effect to detect expressed as a fraction of the observed effect. It specifies that non-time-to-event illustrations are expressed as participants per arm. These are planning assumptions, not a description of this trial’s design, which is single-group. The record does not report the trial’s own sample-size justification. A planning illustration is not observed power and does not show that a completed study had adequate precision.

In general, planning calculations depend on assumptions about the effect to detect, variability, allocation, and statistical procedure. Changing those assumptions changes the planning result. The record does not report the calculated illustration values in the information available for this analysis, and no new planning value can be inferred from the enrollment figure alone. The observed effect required for such an illustration is also not reported as a primary endpoint result.

What can be concluded from the analysis listing?

The registry lists 0 analyses. This means the registry record does not contain listed analysis results for the outcomes described. It does not establish whether analyses were conducted elsewhere, and it should not be interpreted as evidence that there was no analysis outside the registry. The record does not report the statistical plan, adjustment procedures, interim analyses, or analysis populations. These omissions limit the ability to evaluate the methods behind any results not included in the 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("Autologous CD34 Cells")
n   <- c(20)
m   <- c(0.62)
sp  <- c(0.835)
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  Autologous CD34 Cells  20  0.620  0.835  0.229  1.011

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary CFR change and secondary measures of microvascular function, angina, and health-related scores. When multiple outcomes or multiple analyses are considered, general statistical practice recognizes a multiplicity issue: the chance of at least one apparently unusual finding can increase as more hypotheses are tested. Methods for addressing this can include prespecifying a primary outcome, adjusting inference, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy or a detailed statistical analysis plan, so it is not possible to determine how the listed outcomes were prioritized or interpreted statistically.

The registry lists 0 analyses, and it does not report results for the primary or secondary outcomes. It also does not report analysis populations, endpoint-specific denominators, or the number of participants with follow-up measurements. Although enrollment is listed as 20, that figure cannot be assumed to be the number analyzed for each outcome.

Missing data can affect both the estimate and its precision. In general, the consequences depend on why measurements are missing, how much information is missing, and the method used to handle it. A complete-case analysis, an imputation approach, or another method can rely on different assumptions. The registry record does not state whether data were missing, why they may have been missing, or how missingness was addressed. No conclusion about the robustness of an outcome analysis to missing data can therefore be drawn from the registry record.

Analysis populations also matter because the set of participants included in an analysis determines the data summarized. The record does not identify an intention-to-treat, per-protocol, or other analysis population. These are not interchangeable labels to infer from enrollment or completion status. For this study, the statistical treatment of the enrolled group and the handling of participants without endpoint measurements are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute coronary syndrome (5.0%), angina pectoris (5.0%), coronary artery dissection (5.0%), ventricular fibrillation (5.0%), dizziness (5.0%).

The registry lists serious adverse events for the Autologous CD34 Cells group with 20 at risk and 6 affected. It lists 0 deaths. The record also gives 20 at risk and 20 affected for other adverse events. These are registry-reported group figures; they do not provide a detailed account of event timing, severity beyond the serious-event classification, attribution, or recurrence.

The serious-event terms listed are acute coronary syndrome, angina pectoris, coronary artery dissection, ventricular fibrillation, dizziness, and syncope, each with a reported value of 5.0%. These term-specific figures should be read as the registry lists them. The record does not explain whether an individual could contribute to more than one listed term, and the figures should not be added to estimate a total. The listing also does not establish that any event was caused by the intervention.

In general, adverse-event summaries describe events recorded during a study; interpretation depends on definitions, follow-up, ascertainment, and attribution procedures. The registry record does not provide further methodological detail on those procedures. These figures describe the registered safety information and do not by themselves establish comparative risk, because the trial has no control group.

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

The record establishes that a Phase 2 exploratory study of CLBS16 was conducted as an open-label, single-group study in people with coronary microvascular dysfunction and without obstructive coronary artery disease. It identifies change from baseline in CFR at Day 180 as the primary endpoint and lists a range of secondary measures. It also reports summary adverse-event figures for the treatment group. Those are meaningful details about the study question, structure, and recorded safety information.

The record does not report the observed primary endpoint change, its variability, a confidence interval, or a statistical test. It also does not list analyses for the outcomes. Therefore, it cannot show the magnitude or precision of the CFR change, or establish how any primary result relates to a statistical hypothesis. The endpoint description is not a result, and completion status is not evidence of a particular outcome.

Even if a change from baseline were reported, general interpretation of a single-group study would remain distinct from a controlled estimate of treatment effect. Without a concurrent comparison group, change over time cannot by itself identify which factors produced that change. The design can describe what was observed in the treated group, but does not support a randomized comparison with another treatment or control condition.

The adverse-event figures provide a limited description of events in the registry record. They do not establish causation, comparative safety, or a complete account of event patterns. The record does not report additional context such as event timing or attribution procedures. Accordingly, the posted information supports a description of the trial and its recorded safety figures, but not a conclusion about efficacy, treatment effect, or comparative benefit and harm.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly stated physiologic primary endpoint and the absence of a reported primary result in the registry record. The endpoint is change from baseline in CFR at Day 180, with CFR described as a measure of coronary microvascular function. Knowing the endpoint helps clarify what the study set out to assess; without the estimate and its uncertainty, however, readers cannot evaluate the observed magnitude or precision of change.

The single-group, open-label structure is also important. General design principle: a concurrent control group offers a direct reference for distinguishing outcomes under different assigned conditions. In its absence, a baseline-to-follow-up description answers a narrower question about observed change among treated participants. That distinction is essential when interpreting exploratory studies and prevents a within-group change from being mistaken for a controlled treatment effect.

The registry’s list of secondary outcomes spans physiologic, angina-related, and health-related measures. Multiple outcomes can provide a broad view of what a study intended to assess, while also making prespecification and multiplicity handling important for statistical interpretation. The registry record does not report an analysis plan or multiplicity strategy, so the intended inferential role of those outcomes cannot be evaluated from this record.

Finally, the difference between enrollment and analysis is consequential. Enrollment is listed as 20, but the registry does not report endpoint-specific analysis counts or missing-data handling. A reader cannot assume all enrolled participants contributed to every outcome. These design and reporting features make the record useful for understanding the study’s scope, while marking clear limits on what can be concluded about its outcomes.

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.

Several trial-specific limitations affect interpretation of this registry record. The study is single-group, open-label, and has no listed control arm. It therefore does not provide a randomized comparison against another condition. Any within-group change, if reported elsewhere, would need to be interpreted as observed change over time rather than as a controlled estimate of treatment effect.

The primary endpoint result is not reported in the registry record. Neither the mean change in CFR at Day 180 nor its standard deviation, confidence interval, or p-value is listed. The record also lists 0 analyses. This prevents assessment of the outcome’s direction, magnitude, precision, and analytic assumptions from the registry information available.

Although enrollment is listed as 20, the record does not report the number contributing data to the primary endpoint or each secondary outcome. It does not report missing-data amounts or handling, the analysis population, or reasons for any unavailable measurements. The interpretation of endpoint summaries can depend on these details.

The study is described as exploratory, but the registry record does not report the protocol’s statistical analysis plan, sample-size justification, interim analyses, or multiplicity procedures. The listed sample-size assumptions describe a planning illustration rather than the trial’s own design rationale; the record does not provide a trial-specific justification. Finally, the adverse-event summary lacks further detail on timing, attribution, and whether participants could contribute to multiple listed terms. These gaps limit interpretation without implying that unreported procedures or analyses did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Potential Bioactivity of CLBS16 in Patients With Coronary Microvascular Dysfunction and Without Obstructive Coronary Artery Disease — NCT03508609.
• Registry record last updated 2021-01-08; status last verified 2020-11.
• Results first posted 2021-01-08.
• 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

NCT03508609 is a completed Phase 2, open-label, single-group study of CLBS16 in people with coronary microvascular dysfunction and without obstructive coronary artery disease. The registry lists enrollment of 20, a study start of 2018-04-19, and primary completion on 2019-12-10. The treatment is described as a single intracoronary infusion of autologous CD34 cells.

The primary endpoint is change from baseline in coronary flow reserve at Day 180. Seven outcome measures are listed, but the registry record lists 0 analyses and does not report the primary endpoint result. Serious adverse-event figures are listed for the treatment group, including 6 affected and 0 deaths; the term-specific serious-event values are each listed as 5.0%.

The single-group design allows description of outcomes in the treated group but does not provide a control comparison. Missing-data methods, analysis populations, a detailed statistical plan, and the primary endpoint estimate are not reported in the registry record.