Stem Cell Therapy in Patients With Severe Heart Failure & Undergoing Left Ventricular Assist Device Placement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Stem Cell Therapy in Patients With Severe Heart Failure & Undergoing Left Ventricular Assist Device Placement (NCT00869024), a randomized phase 1, phase 2 study. The primary outcome is Safety of Cell Delivery.

2. Clinical Question

The trial’s stated purpose also concerned whether cell delivery after LVAD implantation might help heart function recover and limit later heart enlargement. Those aims provide clinical context, but they are not the posted primary endpoint described in the registry record. The primary outcome is titled “Safety of Cell Delivery” and is defined as the total number of adverse events per group. The registry lists change in left ventricular dimensions and histological assessment among the secondary outcomes, along with the number of participants turned down without meeting LVAD stopping rules.

The registry describes a randomized study with a placebo group, but its design-model label is “single group.” That combination makes the record’s design description difficult to interpret without additional documentation. The primary outcome values are reported for the listed arms, but a two-arm comparison is identified as not estimable. As a result, the posted record does not answer the comparative safety question with an effect estimate or a measure of its precision.

3. Trial Design

ASSURANCE, registered as NCT00869024, is a Phase 1 and Phase 2 study sponsored by the University of Minnesota. Its title describes stem-cell therapy in patients with severe heart failure undergoing LVAD placement. The registry lists the study as randomized and quadruple masked, while its model descriptor is “single group.” It also lists both a Stem Cell Therapy arm and a Placebo arm. These descriptors are not readily reconciled within the registry record, and further details explaining the model label are not reported in the registry record.

The intervention was intramyocardial delivery of bone marrow-derived mononuclear cells. The registry’s study description says that participants’ own cells were to be collected by aspiration from the pelvic bone before the planned LVAD implantation and injected into the heart muscle during surgery. The placebo arm is described as receiving placebo solution injected into the heart muscle. The registry’s brief description places cell delivery just after LVAD implantation.

The listed enrollment is 25. The primary outcome arm entries report n=16 for Stem Cell Therapy and n=4 for Placebo. The adverse-event entries use different at-risk counts for the listed groups. The registry record does not explain these differences, so these counts should be read in the context of the specific outcome entries rather than treated as interchangeable denominators.

The study status is Completed. The recorded start date is 2011-11-10 and the primary completion date is 2016-03-29. The primary outcome timeframe is 24 months. The registry lists six outcome measures, including three secondary outcomes: participants turned down without meeting LVAD stopping rules, change in left ventricular dimensions, and histological assessment. The record does not report details of the randomization procedure, masking implementation, or allocation concealment.

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 Safety of Cell Delivery, measured over 24 months.

The primary endpoint is titled “Safety of Cell Delivery.” It measures the total number of adverse events per group over 24 months. In general, an event-count endpoint captures how many events occur within a group during a defined observation period. It is different from an endpoint that records only whether each participant experienced at least one event: a participant may experience multiple events, and a total count can therefore reflect both the number of affected participants and repeated events.

The registry lists the outcome parameter as NUMBER and the unit as adverse events. It reports a value of 1.0 for Stem Cell Therapy and 0.0 for Placebo. Those values are not accompanied by a spread estimate or interval, and the record identifies the two-arm comparison as not estimable. The posted record therefore does not establish how uncertain the group values are or provide a comparative estimate for the endpoint.

Safety outcomes are used to describe undesirable events observed during a study and to help characterize the safety experience of the interventions being compared. Their interpretation depends on clear event definitions, consistent ascertainment, complete follow-up, and a suitable analysis. The registry record does not provide event-level detail or explain how the primary total was assembled. The serious adverse-event entries are a separate set of safety information and should not be substituted for the total-adverse-event primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching each estimate to its outcome definition, denominator, and analysis. In this trial, the registry describes a count outcome, reports group values, and separately provides participant-level safety summaries. Those summaries answer different descriptive questions. They should not be combined or treated as interchangeable measures.

What does an event count represent?

In general, a count outcome records the number of occurrences during a specified period. For a safety endpoint, the total number of adverse events can include repeated events in the same participant. A count is therefore not necessarily the same as the number of participants who experienced an event. The registry defines the primary endpoint as the total number of adverse events per group during 24 months, but it does not provide event-level data or clarify whether repeated events were counted separately in the posted values.

Count data can have properties that differ from continuous measurements. In general, counts are non-negative and may be concentrated at low values, while some participants may experience more events than others. When the variation in counts exceeds what a simple count model expects, over-dispersion can affect standard errors and confidence intervals. This is a general statistical consideration, not a claim that over-dispersion was assessed in this trial. The registry record does not report a model, a dispersion estimate, or a method for addressing repeated events.

What does a comparison require?

A comparative analysis should connect the group outcome summaries to a clearly defined estimand: the quantity the analysis aims to compare. For an event-count endpoint, the estimand might concern a difference or a relative contrast in event rates, but the registry record does not specify such an estimand or report a rate-based analysis. A meaningful rate comparison also requires information about the time participants were observed and how incomplete follow-up was handled. The record states a 24-month timeframe, but detailed follow-up information is not reported in the registry record.

A confidence interval generally describes the range of values compatible with the data and analysis under the method’s assumptions. It expresses statistical uncertainty, not the probability that a particular effect is true. No confidence interval or other uncertainty measure is reported for the primary values. The record explicitly identifies the two-arm comparison as not estimable. This means the registry does not offer a comparative estimate that can be interpreted with a corresponding precision measure.

How should the group counts be read?

The primary outcome entries report n=16 for Stem Cell Therapy and n=4 for Placebo, while the adverse-event entries report 16 and 9 participants at risk. This variation matters because a count’s meaning depends on who contributed data and for what period. It is not appropriate to assume that the denominators represent the same analysis population or that one set corrects the other. The reasons for the different counts, including whether they reflect missing data, different outcome definitions, or another registry convention, are not reported in the registry record.

In general, a simple comparison of raw counts can be misleading when group sizes or observation times differ. Statistical methods may account for exposure time, repeated events, or other design features, but the registry does not state that such methods were used. No rate, rate ratio, adjusted estimate, or model specification is reported. No new comparison should be inferred from the posted group values alone.

What role does randomization play?

In general, random allocation is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics at the start of a trial, on average. It does not guarantee balance in a particular study, especially when the available groups are small, and it does not remove the need to report how allocation was generated and concealed. The registry labels the study randomized and quadruple masked, and it lists treatment and placebo arms. However, the record’s “single group” model label does not align clearly with those descriptors. The randomization procedure and the meaning of the model label are not reported in the registry record.

Masking can reduce the influence of expectations on care, event reporting, and assessment. The registry’s quadruple-masking label is not accompanied by details identifying which roles were masked or how masking was maintained. The label can be reported, but its practical implementation cannot be evaluated from the registry record.

What do planning illustrations mean?

In general, a sample-size planning illustration estimates how many participants per arm might be needed under specified assumptions to detect a selected effect with a chosen statistical power and significance level. Such an illustration is not the study’s observed result, and it does not show the probability that the trial found a true effect after data collection. The planning assumptions stated for this record refer to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. The record also distinguishes participant-per-arm planning from total-event planning for time-to-event outcomes.

The registry record does not report a trial-specific sample-size justification or the calculations underlying the study design. Any planning illustration based on an observed effect is necessarily conditional on that effect and the stated assumptions. It cannot resolve the missing comparative analysis, establish the reliability of the observed values, or be interpreted as observed power.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: the number of participants turned down without meeting LVAD stopping rules, change in left ventricular dimensions, and histological assessment. It reports six outcome measures overall and zero analyses. Results for the secondary outcomes are not included in the registry record. The record does not state which outcomes were prespecified as primary or secondary in the analysis plan beyond the listed endpoint labels, nor does it report an approach to controlling the risk of false-positive findings across multiple outcomes.

In general, examining multiple outcomes or multiple analyses can increase the chance that at least one result appears notable by chance. Methods for addressing multiplicity include prespecifying a hierarchy, adjusting significance thresholds, or clearly identifying analyses as exploratory. These are general approaches; the registry record does not report which, if any, were used in this trial. There are no posted p-values or secondary-outcome estimates to interpret in light of multiplicity.

Missing-data methods and analysis populations are also not reported in the registry record. The primary outcome arm entries list n=16 and n=4, whereas the adverse-event entries list 16 and 9 at risk. The record does not explain the different denominators or indicate whether all randomized participants were included in each analysis. It does not state how withdrawals, incomplete follow-up, or unavailable outcome measurements were handled.

In general, missing outcome data can affect both the representativeness of a result and its precision. The direction and size of any potential effect depend on why information is missing and how it is handled. Without details about participant flow, follow-up, and analysis populations, the registry values cannot establish whether the posted data include all participants relevant to the intended comparison.

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

Serious events with the highest arm-level rate: increased bleeding (43.8%), any infection (37.5%), increased frequency of ventricular arrhythmias (33.3%), new liver failure (22.2%), new renal failure (22.2%).

The registry reports serious adverse-event information separately from the primary total-adverse-event endpoint. In the Stem Cell Therapy group, 13 participants are listed as affected among 16 at risk; in the Placebo group, 7 are listed as affected among 9 at risk. The death counts are 2 for Stem Cell Therapy and 3 for Placebo. These are descriptive counts from the registry record, not comparative estimates adjusted for follow-up or other factors.

For serious-event terms, the registry lists increased bleeding (43.8%), any infection (37.5%), increased frequency of ventricular arrhythmias (33.3%), new liver failure (22.2%), new renal failure (22.2%), and shock (22.2%). These percentages should be read as reported for the listed terms. The record does not specify their denominators, whether terms could overlap for a participant, or whether the terms refer to event counts or affected participants.

A serious adverse event does not by itself establish that the study intervention caused the event. The registry entries do not give event-level timing, adjudication, or attribution. Nor do the counts alone show how group experience compares after accounting for differences in follow-up or participant characteristics. The primary endpoint’s total adverse-event values and the serious-event summaries describe distinct aspects of safety and should not be substituted for one another.

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

The registry record documents a trial of intramyocardial bone marrow-derived mononuclear cell delivery in the setting of LVAD implantation, with a placebo arm also listed. Its primary outcome is defined as the total number of adverse events per group over 24 months. The posted group values are 1.0 for Stem Cell Therapy and 0.0 for Placebo, while the registry marks the two-arm comparison as not estimable. The record therefore does not provide a quantified comparative result or a measure of the uncertainty around one.

The serious adverse-event entries provide additional descriptive information, including the numbers affected, at-risk counts, deaths, and selected event terms with percentages. These details contribute to the safety record but do not establish causation or resolve the missing primary comparison. The registry does not provide the event-level information or analysis details needed to assess how these safety summaries were derived.

These results do not establish that cell delivery is beneficial or harmful. They also do not establish equivalence between the groups or demonstrate that any observed difference is clinically important. In general, absence of an estimable comparison is not evidence that the groups are the same; it means the registry record does not report a usable comparative estimate for the stated endpoint.

The study’s stated aims included heart-function recovery and limiting heart enlargement. The listed secondary outcomes include change in left ventricular dimensions and histological assessment, but corresponding results are not reported in the registry record. The available endpoint information therefore cannot answer those aims. Additional results, analysis methods, follow-up details, and explanations of the differing denominators would be needed for a fuller assessment of the trial’s findings.

13. Why This Trial Matters Statistically

This trial raises practical statistical questions that are especially important in small clinical studies: whether the registry’s design descriptors agree, whether outcome denominators are clear, and whether a stated endpoint has a reportable comparative analysis. The record labels the study randomized and quadruple masked, lists treatment and placebo arms, and also assigns a single-group model descriptor. Without clarification, readers cannot tell how that model label relates to the described comparison.

Safety outcomes are often summarized in more than one way. A total event count, the number of participants affected, the number of serious events, and the number of deaths are not interchangeable. The registry includes entries for each of these kinds of information, but the primary endpoint is a total adverse-event count and the serious-event entries use at-risk participant counts. Keeping their meanings separate prevents descriptive summaries from being mistaken for a single comparative result.

Denominator transparency is also central. The primary endpoint entries and the adverse-event entries report different group counts. The record does not explain the discrepancy, identify the analysis populations, or describe missing-data handling. Such context is essential for understanding who contributed to each result and how completely the outcomes were observed.

Finally, the record illustrates why a group value alone is not enough for statistical interpretation. A comparative estimate and its uncertainty help distinguish the observed data from what can reasonably be inferred about group differences. The registry explicitly marks the primary comparison as not estimable and reports no analyses. That makes a careful descriptive reading more appropriate than an unsupported conclusion about comparative safety or the trial’s other clinical aims.

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 leaves several trial-specific questions unresolved. It labels the study randomized and quadruple masked, but also identifies the model as single group while listing a treatment arm and a placebo arm. The record does not explain how these design descriptors fit together, how randomization was conducted, or which roles were masked.

The primary outcome is defined as total adverse events per group during 24 months, yet the record does not provide event-level information, an uncertainty estimate, or an estimable two-arm comparison. It does not explain whether the reported values count repeated events or how events were ascertained. The reason the primary endpoint comparison is not estimable is not reported in the registry record.

Denominators differ between the primary outcome entries and the adverse-event entries. The record does not explain these differences, report participant flow, or specify the analysis populations. Missing-data handling, duration of actual follow-up, and treatment of participants with incomplete outcome information are not reported in the registry record.

The registry lists three secondary outcomes but reports no analyses. It does not provide results for the listed secondary outcomes, a statistical analysis plan, a multiplicity strategy, or a trial-specific sample-size justification. The term-specific serious-event percentages are also not accompanied by definitions or denominator details. These limitations restrict interpretation to the registry’s descriptive entries and prevent a complete assessment of the planned analyses or comparative findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Stem Cell Therapy in Patients With Severe Heart Failure & Undergoing Left Ventricular Assist Device Placement — NCT00869024.
• Registry record last updated 2020-03-13; status last verified 2020-02.
• Results first posted 2020-03-13.
• 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

ASSURANCE (NCT00869024) is a completed University of Minnesota-sponsored Phase 1 and Phase 2 trial concerning bone marrow-derived mononuclear cell delivery during LVAD implantation for severe heart failure. The registry describes randomized allocation and quadruple masking, lists Stem Cell Therapy and Placebo arms, and also labels the model single group.

The primary endpoint is total adverse events per group over 24 months. The registry reports values of 1.0 for Stem Cell Therapy and 0.0 for Placebo, but identifies the two-arm comparison as not estimable. Serious adverse-event summaries include affected and at-risk counts, deaths, and selected terms with reported percentages. The record lists three secondary outcomes and six outcome measures, with zero analyses reported. It does not explain the different outcome denominators or provide comparative estimates and uncertainty measures for the primary endpoint.