Serial Infusions of Allogeneic Mesenchymal Stem Cells in Cardiomyopathy Patients With Left Ventricular Assist Device: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Serial Infusions of Allogeneic Mesenchymal Stem Cells in Cardiomyopathy Patients With Left Ventricular Assist Device (NCT03925324), a randomized phase 2 study. The primary outcome is Temperature.

2. Clinical Question

In broad terms, the study was intended to assess the safety and preliminary efficacy of serial intravenous cell infusions in people with heart failure supported by a left ventricular assist device. The registry also lists secondary outcomes concerning NK cell depletion, a cardiac biomarker, right ventricular systolic function, hospitalizations due to right heart failure, six-minute walk distance changes, and gout flares. The record does not provide analyzed results for these outcomes. The clinical question is therefore identifiable from the design and outcome descriptions, but the posted results do not provide an estimate answering whether temperature, or the listed secondary outcomes, differed between the randomized groups.

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled phase IIa study with a parallel-group model. Participants were assigned to human allogeneic mesenchymal bone marrow cells or placebo. The intended intervention schedule was three intravenous infusions, each approximately one month apart. The cell-arm description specifies 1.5 million cells per kg per infusion, administered at approximately 2mL/min, with a maximum dose described for participants at or above 100kg. The placebo description specifies 1.5 mL/kg Lactated Ringer's Solution per infusion. These are planned arm descriptions; the record does not establish how many participants received each infusion.

Enrollment was 4. The registry lists the study as terminated, with a start date of 2019-05-03 and a primary completion date of 2021-08-16. The reason for termination, the timing of the termination decision, and any changes made to the planned conduct are not reported in the registry record. The record identifies Medstar Health Research Institute as the sponsor.

Randomization is intended to make treatment groups comparable on average, while masking is intended to limit the influence of treatment knowledge on care, measurement, and interpretation. Those are general features of randomized and masked designs; the registry does not describe the randomization sequence, allocation concealment, or the specific roles covered by quadruple masking. A parallel-group design assigns participants to one treatment group rather than having each participant receive both interventions in sequence.

The small enrollment and termination are central to interpreting the record. The registry explicitly states that no primary-outcome analysis was performed because of the termination and small sample size. It lists 9 outcome measures and 0 analyses. Details of the protocol's planned analysis, target enrollment, recruitment progress, and sample-size justification are not reported in the registry record. The design description alone therefore cannot establish whether the trial followed all intended procedures or what precision the investigators had planned to achieve.

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:

Analysis population for the primary outcome, as defined in the registry: Due to study termination and small sample size, no analysis was performed

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 Temperature, measured over up to 12 months post enrollment.

The primary outcome is listed as temperature, with a timeframe of up to 12 months post enrollment. Temperature is a measurement of body heat. In general, temperature can be monitored as a physiologic measure and can help identify fever; that general role does not establish the specific rationale or intended interpretation of this trial's endpoint.

The registry record gives the outcome name and timeframe but does not describe the temperature measurement method, measurement occasions, unit, threshold, or analysis summary. It is therefore unclear whether the planned comparison concerned a single reading, repeated readings, a change from baseline, or the frequency of values meeting a defined criterion. The record also does not specify a clinically meaningful difference or how temperature was expected to relate to safety or preliminary efficacy.

The record states that no analysis was performed because the study was terminated and the sample size was small. It consequently contains no reported group comparison, effect estimate, confidence interval, or p-value for temperature. The outcome name indicates what was to be measured, but the registry does not provide analyzed data that would quantify a difference between aMBMC and placebo. Any interpretation of temperature as a particular safety signal or efficacy measure would require details not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how trial observations are converted into estimates and how uncertainty is represented. The registry record describes the randomized, masked, parallel-group design and names outcomes, but it does not report a statistical analysis plan. The primary outcome was not analyzed. The explanations below are general statistical context and do not describe methods confirmed to have been used in this trial.

What does randomization contribute?

In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the time of assignment, including differences that may not be measured. It does not guarantee that the groups will be alike in every characteristic, particularly in a study with very few participants. The registry record identifies the study as randomized but does not report sequence generation, allocation concealment, or the actual allocation process.

Why are masking and a placebo relevant?

In general, masking can reduce the influence of treatment expectations on participant reports, clinical management, outcome measurement, and analysis decisions. A placebo can help make the treatment groups' experiences more similar apart from the active intervention. The registry describes the study as double-blind and quadruple-masked and identifies Lactated Ringer's Solution as the placebo. The specific people covered by each masking description, how similar the infusions appeared, and whether masking was assessed are not reported in the registry record. The labels alone do not establish that masking was successful.

What would an outcome comparison usually describe?

In general, a comparative analysis needs a clearly defined outcome, a population to be analyzed, a time point or follow-up rule, and a statistical summary. For a repeated measure such as temperature, a plan might specify whether to compare readings at particular times, summarize change from baseline, or use a model that accounts for measurements from the same participant. These are examples of possible approaches, not methods reported for this trial. The registry gives no measurement schedule, summary definition, model, or temperature comparison. It says that no primary-outcome analysis was performed.

What does uncertainty mean?

General statistical estimates are subject to uncertainty because the observed participants are only a limited source of information about the groups they represent. A confidence interval is a way to express uncertainty around an estimate: it identifies values that are reasonably compatible with the observed data under the stated statistical model and assumptions. A narrow interval generally indicates greater precision than a wide interval, while neither width nor position alone establishes clinical importance. No primary-outcome estimate or confidence interval is reported in this registry record, so neither the magnitude nor precision of a temperature comparison can be assessed.

A p-value, when used, addresses how unusual the observed data would be under a specified null hypothesis and analysis assumptions. It does not measure the probability that a treatment works, and it does not describe the size or importance of an effect. No p-value for the primary outcome is reported. The absence of an analysis means that a statistical significance interpretation is not available.

Why does a small enrollment matter?

In general, limited information tends to leave estimates imprecise and can make group comparisons especially sensitive to the observations of individual participants. This concern applies to both estimates of benefit and assessments of harm. The registry reports an enrollment of 4 and states that the small sample size contributed to the decision not to analyze the primary outcome. It does not report an effect estimate from which precision could be evaluated. It would therefore be inappropriate to treat the absence of a reported difference as evidence that the groups were equivalent.

General planning calculations for sample size rely on assumptions about the outcome, a target effect, variability, allocation, and the statistical procedure. The registry record does not report the trial's sample-size justification or planned target enrollment. Any sample-size planning illustration should be understood as a hypothetical planning exercise, not as an observed trial result or an assessment of observed power. No such calculation can replace the missing outcome analysis.

What is over-dispersion?

In general, over-dispersion occurs when observed variation in count data is greater than a model assumes. If ignored, uncertainty can be understated and statistical conclusions may be too confident. This concept matters only when an analysis uses an outcome and model for which over-dispersion is relevant. The registry does not report a count-data model or an analysis of the listed outcomes, so there is no basis to say whether over-dispersion was assessed or affected the trial's results.

Other important methods choices include how missing measurements are handled, whether the analysis follows randomized assignment, how repeated observations are modeled, and how multiple outcomes are interpreted. The record does not describe those choices. Without the analysis plan and analyzed outcome data, readers can identify the trial's intended comparison but cannot reproduce or evaluate a statistical result for its primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, time points, or statistical comparisons are examined. In general, testing many hypotheses can increase the chance of obtaining an apparently notable result by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory outcomes can help readers understand how multiple analyses were handled. The registry lists 9 outcome measures and names temperature as the primary outcome. It also lists secondary outcomes, including NK cell depletion, change in a cardiac biomarker, right ventricular systolic function, hospitalizations due to right heart failure, six-minute walk distance changes, and gout flares.

The registry record does not report a multiplicity strategy, a testing hierarchy, or an analysis plan. It reports 0 analyses and says the primary outcome was not analyzed. Thus, there are no posted outcome tests for which adjustment can be assessed, and the record does not support claims based on comparisons among the listed outcomes.

Missing-data handling is also not reported. The registry does not state whether temperature or secondary-outcome measurements were missing, how any missing observations were handled, or whether participants completed the planned follow-up. The primary timeframe is described as up to 12 months post enrollment, but that does not establish the availability or completeness of measurements during that period.

The analysis population is not reported. In general, an intention-to-treat analysis retains participants in their randomized groups, while other analysis populations may depend on treatment received, protocol adherence, or data availability. The registry does not identify which population was planned or used. These omissions matter because analysis choices can affect both the meaning and reliability of a comparison. Given that no primary analysis was performed, the registry record does not provide enough information to evaluate multiplicity, missing-data methods, or analysis-population choices.

11. 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: esophageal obstruction/cancer (50.0%), peg placement (50.0%), abdominal pain/hematemesis (50.0%), acute chronic heart failure (50.0%), sub therapeutic inr (50.0%).

The posted adverse-event counts show 2 participants at risk in the aMBMC group and 2 in the placebo group. Serious adverse events affected 2 participants in each group, and other adverse events also affected 2 participants in each group. The record lists 1 death in each group. These are descriptive counts from a very small enrolled study; they do not establish that the groups had the same safety experience, nor do they provide a precise estimate of comparative risk.

The listed serious adverse event terms are Esophageal Obstruction/Cancer, PEG Placement, Abdominal Pain/Hematemesis, Acute Chronic Heart Failure, Sub Therapeutic INR, and Acute on Chronic Renal Failure. Each is displayed with 50.0%. The record does not provide enough event-level detail to determine timing, recurrence, severity beyond the serious-event classification, or how each term was distributed by arm. The listed terms should not be interpreted as evidence that an event was caused by an infusion.

General safety interpretation considers the number of affected participants, event definitions, timing, severity, treatment exposure, and the completeness of follow-up. With so few participants and no reported comparative analysis, the counts are descriptive rather than conclusive. The registry does not report causes of death or an assessment of whether deaths were related to study treatment.

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

The registry record documents a randomized, double-blind, placebo-controlled phase IIa study of serial intravenous allogeneic mesenchymal bone marrow cells in people with cardiomyopathy and an implanted left ventricular assist device. It gives an intended infusion schedule, identifies temperature as the primary outcome, and lists several secondary outcomes. It also records an enrollment of 4 and a terminated study status.

The primary outcome was not analyzed. As a result, the posted record contains no estimate of the difference in temperature between the aMBMC and placebo groups, and no confidence interval or p-value for that outcome. This is not evidence that there was no effect or that the groups were equivalent. It means that the registry record does not report an analysis from which those questions could be answered.

The safety data report affected-participant counts and deaths in each group, along with serious adverse event terms. These counts are useful as a description of what the record lists, but the small enrollment and lack of detail limit comparative interpretation. The information does not establish causation, exclude uncommon harms, or quantify comparative safety with precision.

In general, a randomized design can support a fair comparison when it is implemented and analyzed as planned, but a design description alone is not a result. Interpretation also requires outcome data, clear definitions, follow-up information, a stated analysis population, and methods for uncertainty and missing data. Those details are not reported for the primary outcome in this record.

The record therefore supports a limited conclusion about the availability of results: a primary-outcome analysis is not posted, and the listed secondary outcomes do not have reported analyses. It does not establish whether the intervention changed temperature, cardiac function, walking distance, hospitalization, or any other listed outcome. Nor does it establish comparative efficacy or safety. Further conclusions would require information not reported in the registry record.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a planned randomized comparison and an analyzed result. The record describes a masked, placebo-controlled parallel-group design, but the primary outcome of temperature was not analyzed. Design features are important for reducing bias, yet they cannot produce an effect estimate when outcome analysis is absent.

Enrollment was 4, and the study is listed as terminated. In a study with very limited enrollment, individual observations can have substantial influence on descriptive summaries and comparisons. The registry itself states that termination and small sample size led to no primary-outcome analysis. The record does not report a sample-size justification or explain why termination occurred, so readers cannot evaluate the original statistical planning or the circumstances behind the termination.

The safety information also shows why counts should be read with their denominators and context. The record lists 2 participants at risk in each group, with serious adverse events and other adverse events affecting 2 in each group, and 1 death in each group. These observations are important to report, but they do not amount to a precise comparison or determine whether an event was caused by treatment.

More broadly, this record highlights the importance of reporting definitions, follow-up completeness, analysis populations, and methods for missing data and multiple outcomes. Without those details and an outcome analysis, readers cannot assess the magnitude or precision of a treatment contrast. The statistically responsible interpretation is neither to claim a benefit nor to claim no effect; it is to recognize that the registry record does not report results capable of answering the primary question.

14. 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 principal limitation is that the registry states that the primary outcome, temperature, was not analyzed because the study was terminated and the sample size was small. No group-level temperature data, effect estimate, confidence interval, or p-value are reported. The record therefore provides no quantitative basis for assessing the primary comparison.

Enrollment was 4. Although the adverse-event entries give group-specific counts, the small amount of information limits interpretation of patterns and makes the record unsuitable for precise comparative conclusions. The reason for termination, participant-level follow-up, and the number of participants who completed the planned infusion schedule are not reported in the registry record.

The temperature endpoint is not operationally defined beyond its name and a timeframe of up to 12 months post enrollment. The measurement method, schedule, summary measure, and threshold are not reported. The registry also does not describe the statistical analysis plan, sample-size justification, analysis population, missing-data handling, or multiplicity approach. It lists secondary outcomes but reports no analyses for them.

Safety interpretation is limited by the absence of event-level details, including timing and causes of death, and by the lack of a reported comparative analysis. The serious-event terms and percentages do not, on their own, establish treatment attribution or allow a detailed assessment of event patterns. The registry record does not describe the methods used to collect or adjudicate adverse events.

Finally, a registered design and arm description indicate the intended study procedures, not necessarily the procedures completed by each participant. The record does not report whether planned doses were received or whether masking was maintained. These limitations mean that the available information is descriptive and incomplete for evaluating efficacy or making a detailed comparison of safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Serial Infusions of Allogeneic Mesenchymal Stem Cells in Cardiomyopathy Patients With Left Ventricular Assist Device — NCT03925324.
• Registry record last updated 2022-02-02; status last verified 2022-01.
• Results first posted 2022-02-02.
• 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.

18. Record Summary

The registry describes NCT03925324, a randomized, double-blind, placebo-controlled phase IIa parallel-group study of human allogeneic mesenchymal bone marrow cells in people with cardiomyopathy and an implanted left ventricular assist device. The comparator was Lactated Ringer's Solution. The intended regimen was three intravenous infusions, approximately one month apart.

The study is listed as terminated, with enrollment of 4. The listed primary outcome was temperature, assessed up to 12 months post enrollment. The registry states that no analysis was performed because the study was terminated and the sample size was small. It lists 9 outcome measures and 0 analyses.

Adverse-event entries list 2 participants at risk in each arm, 2 affected by serious adverse events in each arm, 2 affected by other adverse events in each arm, and 1 death in each arm. The registry does not report an analysis of the primary outcome or analyzed results for the listed secondary outcomes.