Autologous Stem Cells for Cardiac Angiogenesis (FOCUS HF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Autologous Stem Cells for Cardiac Angiogenesis (FOCUS HF) (NCT00203203), a randomized phase 1 study. The primary outcome is Safety of Autologous-bone-marrow Injections.

2. Clinical Question

The registry identifies this as a phase 1 randomized trial with single masking and a crossover model. The listed enrollment is 30. The study’s secondary outcomes covered symptoms, functional classification, oxygen consumption, echocardiographic measures, and imaging-based measures of ventricular function. Those outcomes broaden the clinical context, but the primary question remains safety. The registry record does not report a single combined treatment-effect estimate for safety across the stated assessment times. Consequently, the posted event counts should be read as descriptive information rather than as a definitive comparative answer about risk.

3. Trial Design

FOCUS HF was a randomized, single-blind, phase 1 trial sponsored by the Texas Heart Institute. Its official title describes a trial of autologous bone marrow mononuclear cells under electromechanical guidance for therapeutic angiogenesis. The registry lists ischemic cardiomyopathy as the condition and enrollment of 30. The study is marked completed, with a start of 2004-04 and primary completion of 2008-08.

The active treatment combined bone marrow harvest, processing of the participant’s own cells, and intramyocardial injection guided by NOGA mapping. The control sequence involved NOGA mapping without injections at active enrollment; the registry says that stem cell therapy was offered to this group at 6 months. This sequence is consistent with the registry’s crossover designation. It also means that treatment status changes over time for the control-first group, so a comparison must be interpreted with attention to the assessment period and treatment sequence.

The summary describes extensive baseline testing and follow-up visits after the procedure, including a repeat cardiac catheterization with NOGA mapping at month 6. It also lists follow-up contacts at multiple visits and by telephone. These details describe the follow-up schedule, but the registry record does not report how each scheduled assessment contributed to the primary analysis.

The safety outcome was assessed at up to 2 weeks post-procedure, 3 months, and 6 months. Major adverse events were adjudicated. The registry also lists secondary outcomes involving CCS angina score, NYHA classification, myocardial oxygen consumption, echocardiographic ejection fraction, VE/VCO2 slope, wall motion score index, and SPECT and angiography measures of LVEF. The record does not report a detailed allocation ratio, a statistical analysis plan, or a single primary safety contrast spanning the different assessment times.

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: Adverse events which occurred in all participants.

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 Autologous-bone-marrow Injections, measured over up to 2 weeks post-procedure, 3 months and 6 months.

The primary endpoint concerns safety of autologous bone marrow injections. The registry describes review of adverse events at up to 2 weeks post-procedure, 3 months, and 6 months. It identifies major events for adjudication, including hospitalization, arrhythmia, exacerbation of congestive heart failure, acute coronary syndrome, myocardial infarction, stroke, or death. The outcome is expressed as a number of participants with events, rather than as a continuous measurement such as ventricular function.

Safety monitoring is important in an early-phase trial because the central question is whether concerning events occur during the stated follow-up. Counting participants with events can communicate the observed burden in each reported group. However, counts alone do not establish that an event was caused by the intervention, and they do not by themselves quantify a precise difference in risk between randomized strategies. Interpretation depends on how events are defined, when they occur, how follow-up is handled, and whether the groups are compared over equivalent periods.

The registry describes three assessment times but does not provide a single combined estimate or a separate comparative estimate for each time. The primary outcome has therefore not been reduced to one treatment comparison in the posted results. The available counts should be read as registry safety reporting, not as a complete account of the endpoint’s statistical analysis. The record does not report further details about the endpoint’s analysis population, missing observations, or statistical plan.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the outcome type, the trial sequence, the timing of assessments, and the analysis that was actually reported. The registry identifies the primary outcome as a number of participants with adverse events. Such an outcome is categorical: a participant is counted as having or not having a specified event under the outcome definition. The reported counts describe observed event occurrence, but a count alone is not an estimate of a between-group effect.

What does a count of participants with an event represent?

A participant count is a way to describe how many people in a stated group experienced an event. It differs from counting every event episode: a participant could potentially experience more than one event, while the outcome description is framed as participants with an event. The registry labels separate counts for serious and other adverse events, with at-risk and affected counts for each group. The registry record does not give enough detail to determine whether the same participant could appear in both categories, or how overlapping events were handled. Counts should therefore be interpreted within their specific labels and not combined.

In general, a comparison of event counts may be expressed using a difference in risks, a risk ratio, or another measure. Each measure answers a different question and depends on a defined comparison period and analysis population. No such primary safety effect estimate is reported in the registry information. No new estimate should be inferred from the posted counts without a clearly specified analysis, especially when the groups differ in the reported at-risk counts and treatment changes over time.

Why does the crossover sequence matter?

The trial is described as a crossover model. The control-then-stem-cell group received mapping without injections at active enrollment and was offered stem cell therapy at 6 months. The sequence means the group’s exposure changes over follow-up. A comparison before the crossover can ask about an initial assigned strategy, while a comparison after crossover may involve participants who have received treatment in both groups. Those questions are not interchangeable.

In general, analysis of a crossover design must account for the order and timing of treatment, the period being analyzed, and any effects that persist after an intervention. These considerations are especially relevant when outcomes are safety events observed over time. The registry record does not report a period-specific analysis, a method for handling the crossover, or an assessment of whether effects persisted after treatment. It is therefore not possible to characterize the posted group counts as a clean comparison of treated and untreated follow-up.

What does adjudication add?

The registry says major adverse events were adjudicated. In general, adjudication means that a process is used to review and classify reported events according to specified criteria. This can help make outcome classification more consistent, but the registry information does not describe the adjudication procedures, the reviewers’ masking, or the criteria applied to each event. The event list identifies categories including hospitalization, arrhythmia, exacerbation of congestive heart failure, acute coronary syndrome, myocardial infarction, stroke, and death. It does not give a separate adjudicated count for each category at each assessment time.

How should uncertainty be considered?

In general, a confidence interval communicates statistical uncertainty around an estimated effect. A narrow interval indicates greater precision than a wide interval, while both the estimate and interval need to be considered when judging how much the data distinguish among possible effects. No primary safety confidence interval or comparative effect estimate is reported in the registry record. Nor is an inferential test for the primary safety outcome reported. The descriptive counts therefore cannot be used to claim a precise or statistically established difference between strategies.

Over-dispersion is a general issue that can arise when event counts vary more than a simple statistical model expects. It can make model-based uncertainty estimates too small if not addressed. The posted primary outcome is described as participants with events, and the record does not report a count-model analysis or evidence about over-dispersion. This general concept does not establish that over-dispersion occurred in this trial; it illustrates why the analysis method and its assumptions matter.

What do the planning illustrations mean?

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. In general, such calculations estimate the sample size needed under those assumptions; they are not observed power and do not show that a trial had a particular probability of detecting an effect after the data were collected. The record does not report a sample-size justification for the trial’s own design. Because the primary safety outcome is not reduced to one comparison, the planning assumptions should not be mistaken for a completed analysis of this endpoint.

Important analysis details are not reported in the registry record, including the statistical model for the primary outcome, handling of repeated assessments, analysis population, treatment of missing data, and any adjustment for multiple outcomes or repeated testing. Those omissions limit the degree to which the statistical analysis can be reproduced or independently evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary safety outcome and secondary measures of angina, functional classification, oxygen consumption, echocardiographic function and wall motion, and imaging-based LVEF. Evaluating multiple outcomes can raise the chance of finding an apparently notable result by chance if many hypotheses are tested. In general, multiplicity can be addressed through a prespecified hierarchy, adjustment procedures, or a clear distinction between confirmatory and exploratory outcomes. The registry record does not report a multiplicity strategy.

The primary safety outcome itself has several assessment times: up to 2 weeks post-procedure, 3 months, and 6 months. Repeated assessments can also create multiple possible comparisons. The record does not report whether these times were analyzed separately, combined, or prioritized, and no single primary safety contrast is reported. No analysis entries are reported in the registry information.

The record does not report how missing outcome data were handled, whether every participant contributed at every assessment, or which analysis population was used for the safety counts. It also does not describe exclusions after randomization or how follow-up completeness was assessed. These details matter because event counts depend on who was observed and for what period. They cannot be inferred from the listed enrollment or group counts.

In general, missingness can affect interpretation when the likelihood of an unrecorded outcome differs according to health status, treatment, or follow-up. No assumption about the amount, pattern, or cause of missing data can be made from the registry information. The absence of these details is a reporting limitation, not evidence that missing data occurred or were handled in a particular way.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: placement of aicd (20.0%), pulmonary edema within 24 hrs of treatment (10.0%), replacement of aicd (10.0%), restenosis without symptoms at 6 months, received stent (10.0%), staph aureus septicemia (left sternoclavicular area) leg (10.0%).

The safety listing reports serious adverse events and other adverse events separately. In the control-then-stem-cell group, 7 of 10 participants at risk are listed as affected by serious events, and 9 of 10 by other events. In the stem cell therapy group, 11 of 20 participants at risk are listed as affected by serious events, and 18 of 20 by other events. These are the posted counts, not a time-adjusted comparison or a causal estimate.

The serious-event terms listed include Placement of AICD at 20.0%, Pulmonary edema within 24 hrs of treatment at 10.0%, Replacement of AICD at 10.0%, Restenosis without symptoms at 6 months, received stent at 10.0%, Staph aureus septicemia (left sternoclavicular area) leg at 10.0%, and Urosepsis at 10.0%. The registry information does not provide a group-specific breakdown or explain the denominator for each term. These percentages should not be combined or interpreted as mutually exclusive categories.

The primary safety description refers to multiple assessment times, while the posted counts are not broken down by time. The control-first group was offered cell therapy at 6 months, so exposure also changes over the follow-up period. The record does not report deaths as a count. These limitations prevent the counts from establishing a comparative risk over a common period or identifying which events occurred before or after treatment.

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

The registry record documents a randomized, single-blind, phase 1 study of autologous bone marrow mononuclear cell injections guided by NOGA mapping in ischemic cardiomyopathy. It reports participant counts affected by serious and other adverse events in the two listed groups and gives a list of serious-event terms with percentages. This information describes the safety reporting available in the record.

It does not establish that an event was caused by stem cell therapy. Adverse events can occur during follow-up for reasons unrelated to an intervention, and causal interpretation requires a defined comparison, appropriate timing, and analysis. The record does not provide a time-specific safety comparison, a primary effect estimate, a confidence interval, or an inferential test. The change in treatment sequence for the control-first group further complicates interpretation across follow-up.

The posted counts also do not answer whether cardiac function, symptoms, or other secondary outcomes improved. The registry lists measures such as CCS angina score, NYHA classification, myocardial oxygen consumption, echocardiographic measures, and imaging-based LVEF, but the information does not provide their results. No conclusion about treatment benefit or lack of benefit should be drawn from the safety counts alone.

In general, an early-phase safety study can provide information about observed events and support further questions, but the strength of any conclusion depends on complete reporting and an analysis suited to the design. For this trial, the registry’s available information is best read as descriptive event reporting. It does not supply enough detail to determine how precisely the intervention and control strategies differed in safety, or whether any difference was attributable to treatment.

13. Why This Trial Matters Statistically

This trial illustrates why clinical safety results require more than a list of adverse-event counts. The primary outcome was assessed at multiple times, while the study used a control-first sequence in which the control group was offered cell therapy at 6 months. A meaningful comparison must therefore specify the period being contrasted and account for the changing treatment exposure. Without that temporal context, counts can be mistaken for a stable comparison when they do not represent the same treatment conditions throughout follow-up.

The outcome also distinguishes serious adverse events from other adverse events and identifies event terms. These labels make the safety information more clinically interpretable, but the registry does not report a group-specific, time-specific breakdown for the listed terms. That gap highlights the value of transparent reporting of definitions, denominators, follow-up, event timing, and adjudication procedures.

Statistically, the record illustrates the difference between descriptive data and an inferential treatment comparison. Counts show what was recorded, while an effect estimate and its uncertainty would help characterize the size and precision of a contrast. The registry record does not report those elements for the primary safety outcome. It also does not report the handling of repeated assessments, missing data, or multiple outcomes. These omissions limit reproducibility and caution against drawing stronger conclusions than the posted data support.

Finally, the record lists several secondary clinical and imaging outcomes. Their presence makes it particularly important to distinguish the primary safety question from other possible questions and to know whether analyses were prespecified. The registry information does not describe that statistical plan. FOCUS HF therefore provides a useful example of how trial design, event definitions, timing, and complete analysis reporting all shape what can be learned from safety data.

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 report a detailed statistical analysis plan for the primary safety outcome. It does not specify a model, an effect measure, a confidence interval, or an inferential test. The primary endpoint covers several assessment times, but no single comparative estimate or time-specific analysis is reported. This limits evaluation of the magnitude and precision of any safety contrast.

The crossover sequence is another important limitation for interpretation. The control-then-stem-cell group was initially assigned to NOGA mapping without injections and was offered therapy at 6 months. The event counts are not separated by assessment time or by treatment exposure, and the registry does not describe how crossover was handled analytically. A comparison across the entire follow-up could therefore mix different exposure periods.

The registry does not report how missing observations were handled, whether follow-up was complete for all participants, or which analysis population was used. It also does not explain the denominators underlying the percentages for the listed serious-event terms or provide group-specific values for those terms. Death counts are not reported in the registry record.

Further details about event ascertainment and adjudication are not reported, including the operational definitions applied, the adjudication process, and whether reviewers were masked. The record lists 13 outcome measures but does not describe how multiplicity was addressed or which secondary analyses were prespecified. These are reporting limitations; they should not be interpreted as evidence that a particular method was or was not used outside the information in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Autologous Stem Cells for Cardiac Angiogenesis (FOCUS HF) — NCT00203203.
• Registry record last updated 2016-11-28; status last verified 2016-10.
• Results first posted 2013-01-30.
• 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

FOCUS HF (NCT00203203) is a completed phase 1 randomized, single-blind trial sponsored by the Texas Heart Institute. The registry lists enrollment of 30 and identifies ischemic cardiomyopathy as the condition. The trial evaluated autologous bone marrow mononuclear cell injections into affected left ventricular areas under NOGA electromechanical guidance. Its control-first group received mapping without injections at active enrollment and was offered cell therapy at 6 months.

The primary outcome concerned safety, with adverse events reviewed up to 2 weeks post-procedure, at 3 months, and at 6 months. The registry reports serious and other adverse-event counts by group, along with several serious-event terms. It does not report a single primary safety comparison, an effect estimate, or a confidence interval. The record also lists secondary symptom, functional, and cardiac imaging outcomes, but their results are not included in the information. Important details about statistical methods, missing data, and analysis populations are not reported in the registry record.