A Placebo-Controlled Trial of CLBS16 in Subjects With Coronary Microvascular Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Placebo-Controlled Trial of CLBS16 in Subjects With Coronary Microvascular Dysfunction (NCT04614467), a randomized phase 2 study. The primary outcome is Change From Baseline in Number of Angina Attacks Per Week.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, placebo-controlled phase 2 study. It used quadruple masking, as recorded in the registry. The study title describes evaluation of CLBS16 in subjects with coronary microvascular dysfunction and without obstructive coronary artery disease. The brief description specifies adults currently experiencing angina and a single administration of CLBS16 or placebo. The listed intervention is GCSF-mobilized autologous CD34+ cells; the comparator is placebo.

The registry lists enrollment as 34. The posted primary-outcome summary includes 13 participants in the cell-treatment arm and 12 in the placebo arm. The outcome description cautions that the number contributing to the outcome may be lower than the number in participant flow because of missing data. These figures refer to different reporting contexts, and the registry does not provide enough detail to reconcile them further.

The recorded start date is 2020-10-29, and the primary completion date is 2022-09-28. The study status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain why the study ended or what decisions followed.

The registry record identifies four outcome measures, while no secondary outcome results are posted. The trial's original statistical plan, its sample-size justification, and the details of its analysis populations are not reported in the registry record. The planning figures associated with the posted result are illustrations based on the observed effect, not a description of the original trial design.

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: Note that the number of subjects here may be less than in the participant flow module due to missing data.

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.

Population: Note that the number of patients treated with GSCF-mobilized autologous CD34+ cells here differs from the participant baseline flow module because 2 patients were enrolled in the study but never treated.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Number of Angina Attacks Per Week, measured over Baseline to Month 3.

The primary endpoint is the change from baseline to Month 3 in the number of angina attacks per week. It is a continuous measure summarized by a mean and standard deviation. An attack count captures the frequency of a symptom over a defined period, while measuring change relates the follow-up value to each participant's baseline value. The registry record gives the endpoint unit as angina attacks per week and identifies the timeframe as Baseline to Month 3.

Comparing changes between randomized groups can help describe whether the groups' average symptom trajectories differed during the measured interval. In this trial, the posted group summaries are 1.235 for GCSF-mobilized autologous CD34+ cells and 1.482 for placebo. The registry gives the comparison as a mean difference of -0.247, with the cell-treatment arm as the comparison arm and placebo as the control. These are group-level summaries; they do not show the range of individual experiences or explain whether a particular participant's count changed.

The endpoint is useful for a statistical comparison because it produces a numerical measure that can be summarized and compared across randomized groups. Its interpretation depends on how consistently attacks were recorded, how missing outcome data were handled, and the analysis definition. Those details are not reported in the registry record. The result should therefore be read as a comparison of the posted endpoint summaries, not as a complete account of symptom experience or of every outcome measured in the study.

7. Results Posted in the Registry

• GCSF-mobilized Autologous CD34+ Cells: mean 1.23 versus 1.48 on control; difference -0.25 (95% CI -1.18 to 0.68), standardized effect d = -0.21; z-test p = 0.601.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean difference represent?

The endpoint is continuous, and the registry summarizes each arm with a mean and standard deviation. A mean is the arithmetic average of the outcome values included in the summary. The mean difference compares the two arm means on the original outcome scale. Here that scale is angina attacks per week, and the stated contrast is the cell-treatment arm minus placebo. The reported difference is -0.247. A negative value means the first arm's mean is lower than the comparator's mean; it does not mean that every participant had fewer attacks.

The group summaries are 1.235 for GCSF-mobilized autologous CD34+ cells and 1.482 for placebo. Their standard deviations are 0.989 and 1.337, respectively. A standard deviation describes how spread out individual observations are around their group mean. It is not the uncertainty interval for a group mean or for the between-group difference. The posted pooled standard deviation, 1.168, combines variability information for the standardized comparison.

How should the standardized difference be read?

The registry also reports a standardized mean difference of -0.212. In general, standardization expresses a mean difference in units of a standard deviation, which can help describe an effect without using the endpoint's original measurement scale. The sign retains the direction of the contrast. Standardized estimates depend on the variability used for scaling and should not be treated as a separate outcome. The registry record does not give a clinical threshold for interpreting this standardized value.

What do the confidence interval and p-value describe?

A confidence interval gives a range of values compatible with the data and the method used to calculate the interval. It conveys uncertainty about the estimated mean difference. The posted interval is -1.176 to 0.680. Because it includes the no-difference value, the data are compatible with a range of possible between-group differences in either direction under the stated calculation. A wide interval is less precise than a narrow one, although precision must also be considered in light of the outcome and study design.

The unadjusted p-value is 0.601. In general, a p-value describes how unusual data at least as extreme as those observed would be under a specified null model and its assumptions. It is not the probability that a treatment has no effect, nor does it measure the importance of a result. The registry record does not report a sponsor analysis or detailed assumptions for a trial-specific test. The posted comparison is unadjusted and should be understood in that context.

Why can outcome variability matter?

General statistical explanation: greater variability makes it harder to estimate a group mean difference precisely when the amount of information is otherwise unchanged. The two arm standard deviations are not identical, and the record reports a pooled standard deviation for the unadjusted comparison. If outcome variability differs materially across groups, methods that rely strongly on a common-variance assumption may need scrutiny. The registry record does not state the method used for the original trial analysis, so it is not possible to determine from the posted record whether or how such an assumption was assessed.

Over-dispersion is a general concern when data vary more than a chosen model expects. For a count outcome, a simple model may understate uncertainty if it does not accommodate the observed spread. The primary outcome is a count of angina attacks per week, but the registry summarizes it as a mean and standard deviation. The distribution of individual counts and any model-based analysis are not reported in the registry record. Consequently, no conclusion about over-dispersion or a preferred count model can be drawn from these summaries alone.

What can be said about the analysis populations?

The arm summaries report 13 participants for cells and 12 for placebo. The endpoint description notes that outcome counts may be lower than in participant flow because of missing data. In general, the handling of missing values can affect both the population represented by a result and its uncertainty. The record does not describe imputation, exclusions, or a rule for including participants in the primary analysis. It also does not identify whether the reported group summaries follow an intention-to-treat or another analysis population. Those details are not reported in the registry record.

The posted comparison is an unadjusted recalculation from the reported summary statistics. That kind of comparison does not account for covariates unless they are explicitly incorporated. No adjusted comparison is reported. The registry record also does not report a trial-specific multiplicity procedure, interim analysis plan, or sample-size justification. General statistical explanations of confidence intervals, variability, and testing do not fill in those missing design details.

10. Confidence Intervals and Precision

The mean difference is -0.247, with a confidence interval from -1.176 to 0.680. The interval is the central guide to precision: it shows that the estimated contrast is uncertain and that values in either direction remain compatible with the posted summary-based calculation. It includes the no-difference value, so the point estimate alone should not be treated as a definitive direction of effect.

A confidence interval is not a range containing a fixed proportion of individual participant outcomes. It describes uncertainty about an estimated group-level quantity under the calculation's assumptions. Here, the group standard deviations of 0.989 and 1.337 describe outcome variation, whereas the confidence interval describes uncertainty about the difference between means. The two quantities answer different questions.

The arm summaries include 13 participants for the cell-treatment group and 12 for placebo, and the endpoint note says the number with outcome data may be lower than the participant-flow number because of missing data. The registry does not report the missing-data method or the primary analysis population. Such omissions make it harder to assess whether the interval reflects all randomized participants or a subset with available outcome data.

The unadjusted p-value is 0.601, but a p-value does not replace the interval as a description of the range and direction of plausible differences. The interval is also tied to the unadjusted recalculation, not a sponsor analysis reported in the registry. The original analysis method and its assumptions are not reported in the registry record. Therefore, the interval is informative about the precision of the posted calculation, while leaving uncertainty about the trial's prespecified analysis unresolved.

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 sample-size figures are planning illustrations, not observed trial outcomes. They are expressed as participants per arm, not as a combined total or a total number of events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial's own original design assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the figures are 350 participants per arm for 80% power and 469 participants per arm for 90% power. For planning at 75% of the observed effect, they are 622 participants per arm for 80% power and 833 participants per arm for 90% power. For planning at 50% of the observed effect, they are 1,400 participants per arm for 80% power and 1,874 participants per arm for 90% power.

In general, power is the probability that a study will detect an effect of a specified size under the assumptions used in its planning calculation. The 80% and 90% columns indicate different target probabilities for detecting the stated effect, if the assumptions hold. A higher target generally requires more participants for the same effect. Smaller effects require more participants to detect than larger effects, which is why the planning figures increase as the assumed fraction of the observed effect becomes smaller.

The associated curve illustrates the same planning relationship across the effect assumptions; it is not a record of enrollment or of a trial result. These estimates use the observed effect as their starting point, so they should not be mistaken for the original sample-size justification. This is not observed power.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.248; pooled standard deviation σ = 1.168.
2. n = 2 × (1.96 + 0.842)² × 1.168² / -0.248² = 349.9, rounded up to 350 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
delta <- -0.2475                      # observed difference in means
sigma <- 1.16842442067717                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4614467)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 350 (80% power), 469 (90% power)
 75% of observed effect: n per arm = 622 (80% power), 833 (90% power)
 50% of observed effect: n per arm = 1,400 (80% power), 1,874 (90% power)
power.t.test: 350.8 
Simulated power at n = 350 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, but no secondary outcome results are posted. The primary outcome is the change from baseline to Month 3 in weekly angina attacks. The record does not describe a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for interpreting multiple comparisons. Without those details, it is not possible to determine how the trial's own analysis controlled the risk of false-positive findings across outcomes or analyses.

The posted primary comparison is unadjusted. The record does not report covariate adjustment, an interim analysis plan, or a complete statistical analysis plan. These absences do not show that such procedures were or were not used; they mean that the details are not reported in the registry record. The available p-value should therefore be treated as an unadjusted result rather than as an account of a multiplicity-controlled analysis.

The endpoint description warns that the number of participants contributing to the primary outcome may be lower than the participant-flow count because of missing data. The arm summaries list 13 participants for GCSF-mobilized autologous CD34+ cells and 12 for placebo, while enrollment is listed as 34. The record does not state why the primary-outcome analysis counts differ from enrollment, how much data were missing, or how missing values were handled. It also does not identify the primary analysis population or state whether participants were analyzed according to randomized assignment.

Missingness can affect interpretation if the participants with recorded outcomes differ systematically from those without recorded outcomes. General statistical approaches include explicit assumptions about missing values and sensitivity analyses, but the registry does not say which, if any, were used. The posted result should thus be read as applying to the reported outcome summaries, with uncertainty about how missing data and analysis-population decisions influenced them.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina pectoris (10.0%), atrial fibrillation (7.1%), impaired gastric emptying (7.1%), covid-19 pneumonia (7.1%), bradycardia (5.0%).

The registry reports serious adverse events for 7 of 20 participants at risk in the GCSF-mobilized autologous CD34+ cells group and 2 of 14 at risk in the placebo group. It reports other adverse events for 20 of 20 at risk in the cell-treatment group and 14 of 14 at risk in the placebo group. Deaths are reported as 0 in each group. These are the registry's event counts and denominators; they should not be combined into a new total or treated as a complete description of each participant's experience.

The serious-event terms listed include angina pectoris at 10.0%, atrial fibrillation at 7.1%, impaired gastric emptying at 7.1%, COVID-19 pneumonia at 7.1%, bradycardia at 5.0%, and coronary artery dissection at 5.0%. The record does not clarify whether these listed frequencies refer to each arm or to a combined population, so they should not be assigned to an arm based on the information available.

These figures are descriptive safety reports. They do not establish that an event was caused by an intervention, and they do not support a direct risk comparison without details about event definitions, follow-up, and analysis. Such details are not reported in the registry record.

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

The posted result describes average change in weekly angina attacks from baseline to Month 3 for the reported analysis groups. The cell-treatment arm's mean is 1.235 and the placebo arm's mean is 1.482; the unadjusted mean difference is -0.247. The confidence interval, -1.176 to 0.680, includes differences in both directions, and the unadjusted p-value is 0.601. These statistics describe the available comparison and its uncertainty; they do not prove that the groups are the same or that a difference of any particular size is established.

The estimate does not describe every participant, establish a cause for an individual outcome, or answer questions about outcomes that are not posted. The registry lists four outcome measures but no secondary outcome results. It also does not report the analysis plan, handling of missing data, or a sponsor analysis for the primary endpoint. These limitations matter because the result depends on how the endpoint and analysis population were defined and analyzed.

The study is recorded as terminated. That status is factual, but the reason for termination is not reported in the registry record. It would be inappropriate to infer a reason from the outcome estimate, the safety counts, or the study status alone. Enrollment is listed as 34, while the primary outcome summaries report 13 participants in the cell-treatment arm and 12 in placebo; the endpoint note warns that available outcome counts can be lower than participant-flow counts because of missing data.

Accordingly, the result is best understood as a statistically uncertain, unadjusted group comparison for one symptom endpoint at one stated follow-up. It does not by itself establish clinical benefit, lack of benefit, equivalence, or safety. It also does not resolve how the findings apply beyond the enrolled study population.

16. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between a point estimate and the uncertainty around it. The reported mean difference is negative, but its confidence interval ranges from -1.176 to 0.680 and includes the no-difference value. The point estimate therefore cannot carry the interpretation by itself. The unadjusted p-value of 0.601 likewise does not establish equivalence or settle the possible size and direction of a difference.

The endpoint is a symptom count summarized as a continuous mean and standard deviation. That representation makes a mean comparison possible, but it does not show the distribution of individual counts or explain whether a count-based model was used in the trial's own analysis. The registry record does not report the original statistical method, so the posted summary supports a limited reading rather than a full model-based assessment.

Missing outcome data are also relevant. The endpoint note explicitly allows for fewer participants in the outcome analysis than in participant flow, and the record does not detail how missing values were handled. This leaves uncertainty about the analysis population and about whether the result represents all randomized participants or those with available measurements.

Finally, the planning illustrations show how strongly projected sample requirements depend on the effect size chosen and the desired power. They are based on the observed effect and specified planning assumptions, not on the original design rationale. The study's terminated status and absent reason for termination add context that should not be overinterpreted. Together, these features make careful separation of observed summaries, inferential uncertainty, and unreported design details essential.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several trial-specific questions unresolved. It lists the study as terminated, but the reason for termination is not reported in the registry record. The record also does not explain the relationship between enrollment of 34 and the reported primary-outcome groups of 13 and 12 beyond noting that missing data can reduce outcome counts relative to participant flow. The amount of missing data and its handling are not reported.

The original statistical analysis plan, the sponsor's primary analysis, and the sample-size justification are not reported in the registry record. The posted comparison is unadjusted and based on summary statistics. The record does not provide an adjusted estimate, a detailed analysis population definition, or a prespecified method for handling multiple outcomes. No secondary outcome results are posted, despite the registry listing four outcome measures.

The endpoint is a weekly count of angina attacks summarized with means and standard deviations. The distribution of individual observations, the method of recording attacks, and any model diagnostics are not reported. Without this information, the summaries do not show whether the statistical assumptions of a particular model were examined. The registry also does not describe the precise roles covered by quadruple masking.

Safety reporting is limited to the posted event counts and terms. The registry does not clarify the population basis for the listed serious-event term frequencies, and the counts alone do not establish causality. These limitations do not negate the reported data, but they constrain interpretation and comparison.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Placebo-Controlled Trial of CLBS16 in Subjects With Coronary Microvascular Dysfunction — NCT04614467.
• Registry record last updated 2026-05-04; status last verified 2026-04.
• Results first posted 2026-05-04.
• 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

NCT04614467 is a randomized, parallel, placebo-controlled phase 2 study of CLBS16 in subjects with coronary microvascular dysfunction and without obstructive coronary artery disease. It used quadruple masking and is listed as terminated. Enrollment is recorded as 34; the start date is 2020-10-29, and the primary completion date is 2022-09-28. The reason for termination is not reported in the registry record.

The primary endpoint was change from baseline to Month 3 in angina attacks per week. The posted arm means are 1.235 for GCSF-mobilized autologous CD34+ cells and 1.482 for placebo. The unadjusted mean difference is -0.247, with a confidence interval from -1.176 to 0.680 and an unadjusted p-value of 0.601. The registry record lists four outcome measures and no posted secondary results. The original statistical plan and handling of missing data are not reported.