Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack (NCT01539590), a randomized phase 2 study. The primary outcome is Evaluation of Reduction in Infarct Size.

2. Clinical Question

The clinical question concerns whether adding BB3 to PCI is associated with a difference in the extent of myocardial salvage after a heart attack. Myocardial salvage is intended to represent the portion of threatened heart muscle that is preserved rather than becoming infarcted. The registry describes the primary assessment as an evaluation of reduction in infarct size by MRI, based on an index of myocardial salvage. The record does not provide a unit, summary statistic, or numerical treatment-group result for that assessment.

This was a randomized, parallel-group Phase 2 pilot study. Its small enrollment and the reported early discontinuation in the BB3 group are important context when interpreting the question: the posted record does not establish a precise estimate of a treatment-group difference. It also does not report a statistical test or confidence interval for the primary endpoint. Thus, the registry describes what the study set out to compare, but the posted results do not answer that comparison quantitatively.

3. Trial Design

The registry identifies this as a randomized, parallel-group Phase 2 pilot study. It lists five enrolled subjects: three randomized to BB3 and two randomized to placebo. The study status is terminated. The recorded start is 2012-07, and primary completion is recorded as 2013-07. The reason for termination is not reported in the registry record.

BB3 was described as an adjunct to PCI for subjects presenting with acute STEMI. The BB3 arm description specifies daily intravenous administration of 2 mg/kg for four days. The placebo arm is named Normal Saline and is described as daily intravenous administration for four days. The registry labels masking as quadruple, but the identities of the masked roles are not reported in the registry record. Further details about allocation procedures are not reported in the registry record.

The primary outcome was an MRI assessment at six months, described as an index of myocardial salvage and an evaluation of reduction in infarct size. The registry also lists secondary outcomes covering cardiac biomarkers, heart-failure symptoms and signs, cardiac imaging and function, regional wall motion, myocardial strain, and major adverse cardiac events. The registry record lists 20 outcome measures and zero analyses. It does not report a numerical primary endpoint result or a statistical comparison for that endpoint.

The enrollment and treatment-completion statements require careful distinction. The record says that one of the three subjects randomized to BB3 completed study treatment and that all three discontinued the study prematurely. It says that both subjects randomized to placebo completed study treatment. These statements describe treatment completion and study discontinuation separately; the available record does not clarify their timing or provide a fuller participant-flow account.

Details such as the planned sample-size justification, the specific randomization method, and the statistical analysis plan are not reported in the registry record. The designation as a pilot identifies the study type in the record, but does not by itself establish the intended precision or the rationale for the enrollment target.

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: Five subjects were enrolled into the study; 3 subjects were randomized to BB3 and 2 subjects to placebo. Of the 3 subjects randomized to BB3, 1 completed study treatment; all three subjects discontinued the study prematurely. The two subjects randomized to placebo completed study treatment and neither discontinued the study prematurely.

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 Evaluation of Reduction in Infarct Size, measured over 6 month.

The primary endpoint was an evaluation of reduction in infarct size by MRI at six months, based on an index of myocardial salvage. In broad terms, an infarct-size assessment concerns the amount of heart muscle injured by the heart attack. A myocardial-salvage index is intended to express how much of the myocardium at risk was preserved. This makes it a measure of tissue injury and preservation rather than a direct measure of symptoms alone.

Imaging provides a way to assess cardiac tissue and function after an acute event. In general, a prespecified imaging endpoint can help compare groups using a common measurement at a defined follow-up time. The registry identifies MRI as the assessment method and six months as the timeframe. It does not report the index formula, the MRI acquisition or reading procedures, the scale or unit, or how missing scans were handled. Those details are not reported in the registry record.

The endpoint is described as a comparison between the BB3 and placebo groups, but no group summaries, treatment-effect estimate, confidence interval, or test result for this endpoint are reported in the registry record. Therefore, the endpoint description establishes what the study intended to measure, not the magnitude or precision of any observed difference. The record also indicates that the primary outcome was not reduced to a single comparison in the posted analysis, because it involved several categories or time points.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on separating the study design, the measurements collected, and the analysis actually reported. The registry describes a randomized parallel-group comparison, with BB3 and placebo as the two groups. Randomization is generally used to make treatment assignment independent of measured and unmeasured baseline characteristics on average. In a small study, however, randomization cannot ensure that the groups are similar in every respect. The registry does not report baseline characteristics or details of the randomization procedure, so the balance achieved in this study cannot be assessed from the record.

What does a treatment effect estimate describe?

For a continuous endpoint such as an imaging index, a treatment effect estimate would ordinarily summarize the difference between groups using a clearly specified measure. The interpretation depends on how the index is defined, whether higher values indicate more salvage or more injury, and which analysis population and time point are used. The registry names an MRI-based index of myocardial salvage at six months, but it does not report its unit, formula, group summaries, or treatment-effect estimate. The direction and size of any difference therefore cannot be established from the posted results.

A confidence interval is a general statistical tool for describing uncertainty around an estimate. It gives a range of values reasonably compatible with the data and the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval spanning effects in different directions may leave the direction uncertain. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be evaluated.

Why are group sizes and missing measurements relevant?

The record states that five subjects were enrolled, with three randomized to BB3 and two to placebo. In general, estimates based on small groups tend to be imprecise and can be strongly influenced by individual observations. A small enrollment also limits the ability to characterize uncommon outcomes. These are general considerations; they do not establish the actual uncertainty in this study, because no primary endpoint estimate or interval is reported.

Missing outcome data can affect interpretation if the subjects with observed measurements differ from those without them. The registry reports that one BB3 subject completed study treatment, that all three BB3 subjects discontinued the study prematurely, and that both placebo subjects completed study treatment. It does not report how many six-month MRI measurements were available, whether discontinuation occurred before or after endpoint assessment, or what method was used for missing data. Treatment completion and endpoint availability are not necessarily the same thing, and the record does not provide enough detail to connect them.

What does a comparison of groups require?

A clear group comparison requires a definition of the endpoint, the population to be analyzed, the handling of missing observations, and the statistical method. It also requires a result: usually group summaries and an estimated contrast with uncertainty. The registry does not report these details for the primary endpoint. It lists zero analyses, and the outcome is not reduced to one comparison because it has several categories or time points. Consequently, there is no posted primary comparison to interpret statistically.

For binary outcomes, a comparison might use event counts and a measure of relative or absolute difference; for time-to-event outcomes, analysis would need information about follow-up and event timing. Those are general examples, not descriptions of analyses reported for this study. The registry lists frequency of major adverse cardiac events among secondary outcomes but does not give an analysis or numerical result for that endpoint.

How should multiple outcomes be considered?

Testing many endpoints or time points raises a general multiplicity issue. If many separate tests are conducted, the chance of at least one apparently notable result arising by chance can increase. Prespecifying a primary endpoint and using an appropriate adjustment or hierarchical strategy can help control that issue. The registry lists multiple secondary outcomes and 20 outcome measures, but a multiplicity strategy is not reported in the registry record. The record also does not report which secondary results were analyzed or how they were selected for reporting.

The primary outcome description refers to several categories or time points, and the posted results do not reduce it to one comparison. That makes it especially important not to select one unreported time point or category and present it as the definitive primary result. No such selection or analysis can be reconstructed from the registry record.

What do planning calculations mean?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The planning illustration associated with this study uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; it defines the target effect as a stated fraction of the observed effect. Such calculations are illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect. The registry does not report the trial's own sample-size justification. A calculation based on an observed effect also cannot replace a prespecified design rationale.

In this record, the absence of a numerical primary result prevents an independent assessment of the effect and its uncertainty. Statistical methods can explain what evidence would be needed for a comparison, but they cannot supply an unreported result. The most defensible reading is therefore descriptive: the record identifies the planned endpoint and design, provides limited completion and safety counts, and leaves the primary treatment-group comparison unresolved.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, including a primary MRI-based assessment and secondary measures spanning biomarkers, cardiac function and imaging, symptoms and signs, and major adverse cardiac events. Considering multiple outcomes or time points can raise multiplicity concerns: when many comparisons are examined, some may appear unusual by chance. A statistical plan might address this with a prespecified hierarchy or an adjustment, but such an approach is not reported in the registry record. The posted primary outcome is not reduced to one comparison because it has several categories or time points.

The record lists zero analyses and does not report primary endpoint estimates, confidence intervals, or test results. It also does not report the analysis population definition, missing-data method, or whether the analysis followed randomized assignment. These omissions prevent assessment of the planned inferential approach and how it was applied.

Participant flow is only partly described. The record states that one of the three subjects randomized to BB3 completed study treatment and that all three discontinued the study prematurely; it states that both placebo subjects completed study treatment. It does not explain the timing or reasons for discontinuation, identify which participants contributed endpoint measurements, or report the availability of six-month MRI data. These details are not reported in the registry record, so the effect of missing data on the primary comparison cannot be assessed.

The record's completion statements should not be treated as a substitute for an analysis-population description. Completing treatment does not by itself establish whether a follow-up measurement was available, and premature discontinuation does not by itself establish that all outcome data were missing. The registry does not report the information needed to resolve those questions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry records serious adverse events in two groups. For BB3, zero serious adverse events are reported among three subjects at risk; for placebo, zero are reported among two subjects at risk. These are observed counts in the registry record, not evidence that serious events could not occur or that the groups have equivalent safety.

For other adverse events, the registry reports two affected subjects in the BB3 group among three at risk and one affected subject in the placebo group among two at risk. These counts describe subjects with reported events; they do not state how many events each subject experienced, their severity, timing, or relationship to treatment. The record does not provide serious adverse-event terms, and death counts are not reported in the registry record.

With such small groups, differences in counts are especially difficult to interpret as evidence of a treatment-related pattern. The record does not report a statistical comparison for adverse events. These figures are descriptive and should not be read as a precise estimate of comparative risk or as proof of safety or harm.

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

The registry record identifies a randomized Phase 2 pilot study of BB3 as an adjunct to PCI for acute STEMI, with placebo as the comparator. Its primary question was an MRI-based assessment of myocardial salvage at six months. The record also documents enrollment, limited treatment-completion information, and adverse-event counts. These registry entries describe the design and some reported observations.

What the record does not establish is the numerical result of the primary comparison. It reports no group-level MRI values, estimate of the difference, confidence interval, or test result. Without those, the direction, magnitude, and precision of a primary treatment effect cannot be determined from the posted results. The fact that the study was randomized does not fill in missing outcome results, and the pilot designation does not make a small or absent estimate conclusive.

The participant-flow statements add important context but do not resolve endpoint availability. One BB3 subject completed study treatment, while all three BB3 subjects are described as having discontinued the study prematurely; both placebo subjects completed study treatment. The registry does not explain the timing, reasons, or relationship between these statements and the six-month MRI assessment. Missing-data implications therefore remain unknown.

The adverse-event counts are also limited. Zero serious adverse events are recorded in each group, while other adverse events affected two BB3 subjects and one placebo subject. These descriptive counts, in groups of this size, do not support a precise comparison, and the registry does not report deaths or a safety analysis.

The appropriate statistical conclusion is narrow: the record describes the intended comparison and reports selected counts, but it does not provide enough outcome analysis to quantify the primary difference or its uncertainty. It cannot establish a treatment benefit, lack of benefit, or a comparative safety conclusion.

13. Why This Trial Matters Statistically

This study illustrates why trial design information and trial results must be read separately. The registry identifies randomization, parallel groups, quadruple masking, the treatments, and a six-month MRI endpoint. Those features describe how the comparison was intended to work. They do not, on their own, reveal the treatment-group difference or how precisely it was estimated.

The reported enrollment was five subjects, and the record describes early study discontinuation among the BB3 group. In a small pilot study, participant-level outcomes and missing follow-up can have substantial influence on estimates. This is a general statistical point; the registry does not provide enough primary endpoint data to evaluate its magnitude in this study. The mismatch between a specified imaging question and the absence of numerical imaging results also shows why endpoint definitions, follow-up availability, and analysis reporting are all necessary for interpretation.

The registry lists a range of secondary outcomes, covering several kinds of cardiac measures. Such breadth can be informative for planning later research, but it also makes prespecification and multiplicity handling important. Neither the analysis plan nor a multiplicity strategy is reported in the registry record. With no posted primary comparison, readers should not infer a result from the outcome list or from the safety counts.

Finally, termination status and treatment completion are not substitutes for an explanation of study conduct or a quantitative result. The reason for termination and the relationship between discontinuation and endpoint availability are not reported in the registry record. Statistically, the key lesson is that transparent reporting of estimates, uncertainty, missing data, and analysis populations is essential before a randomized comparison can be judged.

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 record gives no numerical result for the primary MRI endpoint, including no group summaries, treatment-effect estimate, confidence interval, or test result. It also does not describe the index formula, measurement scale, MRI reading procedures, or handling of missing scans. These omissions prevent assessment of the primary comparison's size, direction, precision, and reproducibility.

The small enrollment and the reported BB3 discontinuations limit what can be learned from the posted record. The registry says that one BB3 subject completed study treatment and that all three BB3 subjects discontinued the study prematurely; both placebo subjects completed study treatment. Reasons and timing are not reported, nor is the availability of six-month endpoint data. Thus, the consequences of attrition for the primary outcome cannot be determined.

Further limitations include no reported sample-size justification, analysis plan, randomization procedures, analysis-population definition, missing-data method, or multiplicity strategy. The registry lists several secondary outcomes and 20 outcome measures, but it records zero analyses. The reason the study was terminated is not reported in the registry record. Serious adverse-event counts are reported, but the record provides no serious event terms; other adverse-event details and death counts are also limited or unreported.

These are limits of the registry record and the posted results. They do not explain why information is absent or establish what the investigators may have observed outside the reported record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack — NCT01539590.
• Registry record last updated 2014-11-21; status last verified 2014-11.
• Results first posted 2014-11-04.
• 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.

18. Record Summary

The registry describes a randomized, parallel-group Phase 2 pilot study of BB3 as an adjunct to PCI for subjects presenting with acute STEMI. It lists five enrolled subjects: three randomized to BB3 and two to placebo. BB3 was described as 2 mg/kg by daily intravenous administration for four days; normal saline was the placebo, administered daily for four days. The primary outcome was an MRI-based index of myocardial salvage at six months.

The record states that one BB3 subject completed study treatment and all three BB3 subjects discontinued the study prematurely; both placebo subjects completed study treatment. It reports zero serious adverse events in each group and other adverse events affecting two BB3 subjects and one placebo subject. The study status is terminated.

Numerical results for the primary endpoint, statistical analyses, the reason for termination, and the trial's statistical analysis plan are not reported in the registry record. The posted information therefore describes the study and selected counts but does not quantify the primary treatment-group comparison.