Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration (NCT01458405), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants Experiencing Any of the Adjudicated Events.

2. Clinical Question

The registry title describes a safety and efficacy study, and the brief summary says its purpose was to determine whether CAP-1002 is safe and effective in decreasing infarct size after myocardial infarction. These statements describe the study’s aims, not findings. The primary outcome listed in the record is a safety count, while the listed secondary outcomes include measures of left ventricular function, volume, and infarct size at Month 6 and 12.

The record also reports adverse-event counts by study group. Those figures describe participants with reported events in the listed groups; they do not, by themselves, establish that a particular event was caused by the intervention. Because the registry record does not report the primary-endpoint comparison or detailed results for the secondary outcomes, the stated clinical aims cannot be judged from those aims alone.

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase I/II study. The official title describes it as double-blind and placebo-controlled, while the registry design information labels masking as triple. Randomization and masking describe intended features of the study design; they do not establish how successfully masking was maintained or what results followed.

The record lists enrollment as 135 and the study status as terminated. The recorded study start was 2012-11-13, and primary completion was 2017-07-03. The record does not report why the study was terminated, so the status alone should not be read as evidence about safety, efficacy, feasibility, or the reason for stopping.

The study included a Phase 1 safety cohort and a Phase 2 randomized treatment cohort. Phase 1 group labels identify a safety cohort receiving 12.5 M CDCs and another receiving 25 M CDCs. The Phase 2 groups are placebo and CAP-1002 allogeneic cardiosphere-derived cells. The registry record does not provide further arm descriptions or explain the relationship between the phases beyond these labels.

The primary outcome was specified as the number of participants experiencing any of the adjudicated events within 1-month post-infusion. The record says this measure was not planned to be collected and reported for Phase 1. It also identifies the analysis population for this outcome as a safety population comprising participants who received investigational product. This differs in concept from an analysis restricted to everyone randomized, and the record does not provide a detailed account of the population used for each other outcome.

The Phase 2 adverse-event groups are reported as placebo and CAP-1002, with the group counts and event counts described in the safety discussion. The registry record does not report the randomization procedure, allocation concealment, protocol deviations, treatment discontinuations, or whether every randomized participant contributed data to every outcome. Those details matter when evaluating how closely the analyzed groups preserve the benefits of randomization.

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.

Before assignment: After completion of screening procedures, and at least 4 weeks after myocardial infarction (MI), eligible Phase 1 participants received CAP-1002. In Phase 2, participants were randomized in 2:1 ratio to receive treatment with either CAP-1002 or placebo. Based on available clinical data at time of analysis, Sponsor decided not to pursue development of CAP-1002 in this indication; hence trial was stopped. Outcome measures data was planned to be collected and reported for Phase 2 part of study.

Phase 1 (up to 12 Months)

Reasons for not completing this period:

Phase 2 (up to 12 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on safety population that included all participants who received investigational product. Data this outcome measure was not planned to be collected and reported for Phase 1 part of the 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.

Population: Analysis was performed on safety population that included all participants who received investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing Any of the Adjudicated Events, measured over Within 1-month post-infusion.

The primary endpoint counts participants who experienced any of the adjudicated events within 1-month post-infusion. The events listed are acute myocarditis; death due to ventricular tachycardia or ventricular fibrillation; sudden unexpected death, defined as occurring within one hour of symptom onset or as an unwitnessed death; and major adverse cardiac events. The latter is defined as a composite incidence of death, non-fatal recurrent myocardial infarction, hospitalization for heart failure, emergency room treatment for heart failure, left ventricular assist device placement, or heart transplant.

A count of participants with at least one event can provide a direct summary of how many people experienced a specified safety outcome during the stated period. A composite endpoint can include several clinically distinct events, making the result sensitive to the definition and components of the composite. The record does not provide component-level primary-endpoint results, so it is not possible to tell from the primary outcome description which components, if any, contributed most to a group’s result.

The registry identifies the safety population as participants who received investigational product and says the primary measure was not planned for the Phase 1 part. However, a primary-endpoint comparison or result is not reported in the registry record. The endpoint definition therefore explains what was intended to be counted, but does not establish the observed frequency or any difference between the randomized groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as binary in the sense that each participant either experienced at least one qualifying event during the stated period or did not. The reported outcome is a count of participants with an event, rather than a continuous measurement such as a change in ventricular volume. For a binary endpoint, a treatment comparison can be expressed using several kinds of effect measure, but the registry record does not specify or report one for the primary endpoint.

What does an effect estimate describe?

An effect estimate summarizes the observed contrast between groups according to a chosen statistical measure. For a binary endpoint, a contrast might focus on the difference in event probabilities or another relative measure. The interpretation depends on which measure was prespecified and on how the analysis population and missing observations were handled. The registry record does not identify a primary effect measure or give a numerical primary-endpoint estimate, so no particular contrast should be attributed to this study from the information reported.

A confidence interval describes the range of values compatible with the data under a statistical model and its assumptions. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies within the interval. A narrow interval indicates greater precision than a wide interval, while neither width nor location can be assessed when an interval is absent. No confidence interval for the primary endpoint is reported in the registry record.

Why does the analysis population matter?

The record says the primary outcome analysis used a safety population that included all participants who received investigational product. That is a treatment-received definition, rather than an explicit statement that every randomized participant was analyzed in the group originally assigned. In a randomized trial, analyzing participants according to original assignment is often used to preserve the comparability created by randomization. A safety analysis may instead focus on those who received treatment. These approaches answer different questions, and the registry record does not provide enough detail to determine how any participants not receiving assigned treatment were handled.

The record states that primary-outcome collection and reporting were not planned for Phase 1. This means Phase 1 should not be treated as having a comparable primary-endpoint result simply because its adverse events are listed. The primary safety outcome is described for the safety population, but a complete accounting of group membership, follow-up, and endpoint availability is not reported.

What can be learned from event counts?

Counts are useful for describing what was recorded in each group, but a count alone does not quantify uncertainty or establish a between-group effect. The denominator matters, as does whether participants had comparable opportunity for follow-up. For an outcome that can occur more than once per person, event counts and counts of affected participants are also different summaries. The primary endpoint is specifically phrased as participants experiencing any qualifying event, while the listed adverse-event fields separately report participants with serious or other adverse events. The record does not provide a detailed statistical analysis explaining how recurrent events or timing were handled.

The primary endpoint combines multiple event types, including events with different clinical meanings and potentially different frequencies. For composite outcomes, an overall result can be influenced by the components that occur more often. Component-specific results help readers understand that composition, but are not reported for the primary endpoint in the registry record. The endpoint definitions identify the components; they do not show how frequently each occurred.

What is known about the statistical plan?

The registry record does not report the statistical test or model used for the primary outcome, a prespecified hypothesis, adjustment variables, or a decision rule for interpreting the primary comparison. The number of analyses listed in the record is 1, alongside 24 outcome measures, but the record does not explain the relationship between that listing and the full analysis plan. It is therefore not possible to verify from the registry information which analyses were prespecified, which were exploratory, or whether any adjustments were made.

The record includes sample-size planning illustrations described as using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are described as planning illustrations based on an observed effect, not as the trial’s own design justification. They do not establish the original enrollment rationale, and planning sample sizes are not observed power. The registry record does not report the protocol’s sample-size justification or the assumptions used for the original design.

In general, a significance test evaluates how compatible data are with a specified null model, given the model assumptions. A p-value does not measure the probability that a treatment works, nor does it describe the magnitude or clinical importance of an effect. The registry record does not report a primary-endpoint p-value, and none should be inferred from the adverse-event counts alone.

Because the primary outcome has multiple categories or time points, it is not reduced to one comparison in the statistical summary. This preserves the distinction between the endpoint’s components and avoids implying a single result where the record does not supply a complete comparative analysis. No recalculated estimate is presented for that endpoint in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures and identifies secondary outcomes covering adjudicated events, left ventricular ejection fraction, left ventricular end diastolic volume, left ventricular end systolic volume, and myocardium mass infarct size. Several measures are specified as absolute or percent change from baseline at Month 6 and 12. Examining multiple outcomes or time points creates multiple opportunities to observe apparently noteworthy results by chance. Statistical approaches to multiplicity can control that risk, but the registry record does not report whether any adjustment was planned or applied.

The record lists 1 analysis, but does not explain how that listing relates to the outcome measures, whether a hierarchy was prespecified, or which outcomes were treated as confirmatory. The titles of the outcomes alone are not sufficient to establish an analysis hierarchy. Without that information and the corresponding results, readers cannot assess the role of multiplicity in interpreting any apparent secondary finding.

Missing-data handling is not reported in the registry record. The record does not provide outcome-specific numbers of participants assessed, reasons for missing observations, follow-up completeness, or the methods used to address missing values. These omissions are especially relevant for outcomes described as changes from baseline at later visits, because the interpretation depends on who contributed measurements and how unavailable measurements were handled.

The primary safety outcome is defined for participants who received investigational product, and the record says it was not planned for Phase 1. It does not provide a full account of exclusions, withdrawals, or the number assessed for this endpoint in each Phase 2 group. The adverse-event counts should therefore be interpreted in the context of the reported group denominators, without assuming that follow-up or data availability was identical across groups.

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: acute myocardial infarction (6.8%), implantable defibrillator insertion (6.5%), cardiac failure congestive (4.5%), angina pectoris (3.9%), iron deficiency anaemia (2.3%).

The registry reports serious adverse-event counts for each named group: 0 of 4 in the Phase 1 cohort labelled 12.5 M CDCs; 0 of 10 in the Phase 1 cohort labelled 25 M CDCs; 15 of 44 in the Phase 2 placebo group; and 20 of 77 in the Phase 2 CAP-1002 group. For other adverse events, the counts are 4 of 4, 10 of 10, 24 of 44, and 42 of 77, respectively. Deaths are listed as 0 in each group.

These are descriptive counts, not estimates of causation. The Phase 1 groups are safety cohorts rather than the randomized placebo comparison, so they should not be treated as equivalent randomized arms. Even for Phase 2, counts alone do not show whether group differences are statistically precise or whether they reflect treatment, chance, follow-up, or other factors. The registry record does not report confidence intervals or a statistical comparison for these adverse-event counts.

The listed serious-event terms and percentages are not accompanied by a group-specific breakdown in the registry record. They should be read as reported event summaries, not as proof that events were caused by CAP-1002 or placebo. A zero death count does not establish zero risk, and the reason the study was terminated is not reported.

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

The record establishes that a randomized, masked, placebo-controlled Phase I/II study was conducted and that its stated aims included safety and efficacy after myocardial infarction. It also identifies the primary safety outcome, gives counts of participants with serious and other adverse events by group, and lists several secondary measures of cardiac function and infarct size.

What the record does not establish is whether CAP-1002 changed the primary endpoint relative to placebo. The primary-endpoint comparative result, effect estimate, confidence interval, and p-value are not reported in the registry record. The presence of an endpoint definition is not evidence of a favorable or unfavorable result. Similarly, the secondary outcome titles do not supply results for left ventricular function, volume, or infarct size.

The adverse-event counts describe events recorded within the listed groups. They do not, without an appropriate comparison and information about uncertainty, establish that the intervention caused more or fewer events. Event descriptions and percentages also do not determine whether an event was treatment-related. The registry record does not provide the detail needed to make such attribution.

The status of terminated is also not an efficacy finding. The record does not state why the study ended, nor does it report whether termination followed a planned decision, a safety concern, recruitment considerations, or another reason. Any such explanation would be speculation.

For statistical interpretation, the central distinction is between a study’s question and its answer. The study aimed to evaluate safety and efficacy, but the registry information contains only selected safety counts and study descriptions rather than a complete comparative analysis. The registry entries therefore support a description of design and reported events, not a conclusion about treatment benefit or absence of benefit. They also do not support medical recommendations.

13. Why This Trial Matters Statistically

This study is statistically notable because its registry record combines early-phase safety cohorts with a randomized Phase 2 treatment comparison. Those parts serve different purposes and should not be conflated. The Phase 1 cohorts are identified by dose labels, while placebo and CAP-1002 form the randomized treatment groups. A comparison across all groups would not have the same interpretation as the randomized Phase 2 contrast.

The primary outcome is a safety composite that counts participants experiencing any of several adjudicated events within 1-month post-infusion. Composite endpoints can give a compact summary, but their interpretation depends on the mix of component events. Without component-level counts, readers cannot determine which events shape the overall measure. The record defines the components but does not report the primary-endpoint results.

The registry also lists multiple secondary outcomes involving changes in ventricular function, ventricular volumes, and infarct size at Month 6 and 12. Such outcomes broaden the scientific questions but make transparent reporting of analysis plans and multiplicity important. The registry record does not report an adjustment strategy or the details needed to establish how confirmatory claims would be distinguished from exploratory findings.

Finally, this record illustrates why a study’s status, endpoint definitions, and adverse-event summaries cannot stand in for a comparative analysis. The record identifies the study as terminated and reports event counts, but does not explain the termination or provide primary comparative results. Statistical interpretation depends not only on what was measured, but also on the analysis population, follow-up, uncertainty, and prespecified analysis. Several of those details are not reported in the registry record.

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 registry record does not explain why the study was terminated. Without that information, termination cannot be interpreted as a response to safety, a lack of efficacy, recruitment difficulty, or any other specific circumstance.

The primary safety endpoint is described, but its comparative result is not reported. The record does not provide an effect estimate, confidence interval, p-value, component-level results, or a statistical method for comparing the randomized groups. This prevents assessment of the magnitude and precision of a primary-endpoint contrast.

The primary endpoint was not planned to be collected and reported for Phase 1. The Phase 1 safety-cohort counts consequently do not provide the same primary-endpoint information as the randomized Phase 2 comparison. The record does not provide fuller details about how participants were followed or how endpoint data were handled.

The record lists 24 outcome measures but does not describe a hierarchy, multiplicity adjustment, or which analyses were confirmatory. It also does not report missing-data methods, outcome-specific follow-up completeness, or reasons for unavailable measurements. These omissions limit interpretation of the listed secondary outcomes, particularly those involving change from baseline at Month 6 and 12.

Adverse-event counts and selected serious-event percentages are reported, but the registry record does not provide confidence intervals, a group-specific breakdown for the listed serious-event terms, or evidence that events were attributed to study treatment. The record also does not provide detailed arm descriptions, the randomization procedure, allocation concealment, or information on protocol deviations. These gaps constrain assessment of the trial’s conduct and the robustness of any comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration — NCT01458405.
• Registry record last updated 2024-04-09; status last verified 2024-02.
• Results first posted 2024-04-09.
• 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 record describes NCT01458405, titled “Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration,” as a randomized, triple-masked, parallel Phase I/II study. Its official title describes intracoronary delivery of allogeneic cardiosphere-derived cells in patients with a myocardial infarction and ischemic left ventricular dysfunction. Enrollment is listed as 135; the recorded start is 2012-11-13, primary completion is 2017-07-03, and status is terminated.

The primary outcome is the number of participants experiencing any adjudicated event within 1-month post-infusion. It was not planned for Phase 1, and a comparative primary-endpoint result is not reported in the registry record. The record gives serious and other adverse-event counts by group and lists secondary measures of ventricular function, volumes, and infarct size. It does not report the reason for termination, primary comparative statistics, missing-data handling, or a detailed statistical plan.