Building Strength Through Rehabilitation for Heart Failure Patients (BISTRO-STUDY): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Building Strength Through Rehabilitation for Heart Failure Patients (BISTRO-STUDY) (NCT03615469), a randomized na study. The primary outcome is Change in 6 Minute Walk Test.

2. Clinical Question

The clinical rationale in the registry focuses on poor functional status in heart failure and the difficulty some patients have tolerating or sustaining exercise. It proposes NMES as a way to support the initiation of quadriceps strengthening. The registry background describes exercise as a recommended component of heart failure management and notes concerns about adherence. Those statements explain why the investigators proposed the intervention; they are not findings from this study.

The primary question is about a measured walking outcome over the stated follow-up interval. It is not a direct test of every aspect of functional status, quality of life, symptoms, hospitalization, or mortality. Although the registry background discusses those broader concerns, the primary outcome listed in the record is the 6 Minute Walk Test. No secondary outcomes are posted. The record therefore supports a focused description of the walking-test summaries and their reported statistical comparison, rather than conclusions about other outcomes.

3. Trial Design

The registry identifies BISTRO-STUDY as a randomized, quadruple-masked, parallel study sponsored by Indiana University. The recorded phase is NA. The study status is terminated. Enrollment is listed as 15, with a start date of 2018-09-06 and primary completion date of 2020-07-01. The registry record does not state why the study was terminated, so no reason can be inferred from the status alone.

The two named interventions are neuromuscular electrical stimulation and transcutaneous electrical stimulation. The arm descriptions characterize the latter as the sham group: it uses the same electrode landmarks, with a TENS setting intended to produce intermittent tingling rather than the NMES setting. The intervention description for NMES includes a simultaneous large-muscle atrophy setting and electrode placement on the thighs, but its text is cut off in the record. Further details about implementation are not reported in the registry record.

The posted primary outcome is change in the 6 Minute Walk Test from baseline to 5-6 months. The record describes the outcome as a mean with standard deviation and gives the unit as meters walked. In the NMES arm, the posted summary has a mean of 324.0 and a standard deviation of 198.9, with n of 3. In the transcutaneous electrical stimulation arm, the mean is 250.6 and the standard deviation is 231.7, with n of 5. The registry lists one analysis of this outcome.

Randomization and masking describe intended design features, but the posted record does not explain the sequence-generation method, allocation concealment, who was masked, or whether masking was maintained. The registry does not report the reasons for the enrollment total, a sample-size justification, or whether the study ended as planned. The enrollment figure and outcome-specific group counts are different record entries; the registry does not reconcile them. No further design details should be assumed from the labels alone.

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

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 Change in 6 Minute Walk Test, measured over From Baseline to 5-6 months.

The primary endpoint is change in the 6 Minute Walk Test from baseline to 5-6 months, reported in meters walked. The test measures the distance a participant can walk during a set time period. The registry explains that participants are asked to move as quickly as they feel safe and comfortable over a 100-meter course for 6 minutes, may use an assistive device, and may stop and rest when necessary.

The registry describes the test as an estimate of a person’s ability to perform everyday activities and as a measure of exercise capacity. It states that the test is recommended by the American Thoracic Society for people with moderate to severe heart or lung disease. These statements explain the rationale for selecting the endpoint; they do not establish that the test captures every dimension of daily function or heart failure status.

Because the endpoint is a continuous measurement, the posted summaries use means and standard deviations. The mean describes the average recorded outcome within an arm, while the standard deviation describes the spread of individual measurements around that mean. A mean alone does not reveal how participants’ values were distributed or whether a small number of values strongly influenced the average.

The registry’s endpoint title says “Change in 6 Minute Walk Test,” and its timeframe is baseline to 5-6 months. It does not give a more detailed definition of how change was calculated, how missing follow-up measurements were handled, or which analysis population was used. Those details are not reported in the registry record. The outcome summaries should therefore be read as the posted descriptions of the endpoint, not as a complete account of its derivation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry records a two-sided t-test for the primary continuous outcome. A t-test compares group means, with the exact form and assumptions depending on how the analysis is specified. The record does not give further detail about the version of the test, any adjustment, or the handling of missing data. It reports p = 0.22, but does not provide the test statistic, degrees of freedom, estimated group contrast, or confidence interval.

What does a two-sided test mean?

In general, a two-sided test evaluates departures in either direction from the null value. For a comparison of group means, it considers whether the data are compatible with no mean difference while allowing for a contrast in either direction. The p-value is calculated under the null hypothesis and the assumptions of the analysis. It is not a measure of the probability that the null is true, and it does not indicate the probability that the result will be replicated. The registry reports the test as two-sided; further details about its prespecified role are not reported.

What information do the means and standard deviations provide?

For a continuous outcome, the mean is a summary of the center of the observed values. The standard deviation describes dispersion around that mean. Here the posted mean and standard deviation are 324.0 and 198.9 for NMES, and 250.6 and 231.7 for transcutaneous electrical stimulation. The corresponding outcome-specific counts are n of 3 and n of 5. These summaries do not reveal the distribution’s shape, the presence of unusually influential observations, or whether values were missing for participants who enrolled. Participant-level measurements are not reported in the registry record.

In general, a standard deviation is not the same as a standard error or a confidence interval. The standard deviation describes variability among observations; a standard error describes uncertainty in an estimated quantity, and a confidence interval expresses a range of values compatible with the data and analysis assumptions. The registry gives standard deviations but does not report a confidence interval for the group contrast. It is therefore not possible to characterize the precision of the comparison using a posted interval.

Why is the confidence interval important?

In general, a confidence interval helps readers assess both the direction and the precision of an estimated effect. A narrow interval indicates greater precision under the model; a wide interval indicates less precision. It also makes clear which effect sizes remain compatible with the data. A p-value alone does not supply that information. Since the registry reports neither a contrast estimate nor its confidence interval, the comparison’s magnitude and precision are not directly stated in the posted results.

What does over-dispersion mean for interpretation?

In general, over-dispersion means that the observed data vary more than a model or simplifying assumption would expect. It matters because a method that understates variability can make uncertainty look smaller than it is. The registry reports standard deviations for this continuous endpoint, not a count outcome, and does not report a separate over-dispersion analysis. The relatively large reported standard deviations indicate spread in the observations, but they do not by themselves establish that a formal over-dispersion model applies. Any model-specific claim beyond the posted t-test is not reported in the registry record.

Can the comparison be recalculated?

The registry record does not provide a recalculated effect estimate or confidence interval for this comparison. The available summary values are not accompanied by a posted unadjusted recalculation. The record’s analysis listing gives the test type and p-value only. It would be inappropriate to present a newly calculated contrast or precision measure as though it were a registry result. No discrepancy between a recalculation and the sponsor’s result is flagged in the record, and no recalculated values are available to compare.

How should the planning assumptions be understood?

The registry’s planning assumptions describe an illustration based on the observed effect, not the study’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning convention is participants per arm for a specified power. These are general planning concepts, not evidence that the trial was designed with those assumptions, and they are not observed power. The registry does not report the study’s own sample-size justification or statistical plan. No additional sample-size conclusions can be drawn from the planning assumptions alone.

In general, a sample-size calculation asks how many participants would be needed under specified assumptions about the target effect, variability, significance level, allocation, and desired power. A planning illustration can show how assumptions affect a future study design, but it does not change what was observed in this study. It cannot remedy the lack of a posted confidence interval or resolve the difference between total enrollment and outcome-specific counts. The registry does not report interim analyses, stopping criteria, or the role of any planning calculation in the conduct of this study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Neuromusclar Electrical Stimulation", "Transcutaneous Electrical Stimulation")
n   <- c(3, 5)
m   <- c(324, 250.6)
sp  <- c(198.9, 231.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Neuromusclar Electrical Stimulation  3  324.000  198.900  -170.095  818.095
CARM  Transcutaneous Electrical Stimulation  5  250.600  231.700  -37.094  538.294

11. Analyses Reported by the Sponsor

The registry’s own analysis is a two-sided t-test with p = 0.22. The record does not report the sponsor’s estimated between-arm difference, confidence interval, test statistic, or further details of the analysis. The posted arm summaries are means and standard deviations for the primary outcome, with outcome-specific counts of n of 3 and n of 5.

No recalculated comparison is available in the registry record, so there is no separate recalculated estimate to set alongside the sponsor’s test result. The record does not flag a discrepancy between the sponsor’s analysis and a recalculation. The sponsor’s reported analysis therefore remains the available inferential result; it should not be replaced by an unreported calculation or by a contrast inferred from the group means.

As a general statistical point, a simple unadjusted re-calculation from summary statistics can be useful as a check when the necessary inputs and a suitable analysis are available. Such a calculation may differ from a sponsor’s analysis if the methods, analysis populations, or assumptions differ. That is not a documented issue in this record, and no alternative estimate or reason for a difference is reported. The most transparent reading is to distinguish the posted group summaries from the reported t-test and to note that the effect estimate and its precision are absent.

The reported p-value does not provide a measure of the effect’s size and cannot replace an interval estimate. The registry also does not state whether the reported test was prespecified or adjusted for any other analysis. Details of the sponsor’s statistical plan are not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and one analysis, and it reports zero secondary outcomes posted. This limits what can be said about multiple testing from the available record, but it does not establish that the study protocol contained no other planned outcomes or analyses. The full statistical plan and analysis protocol are not reported in the registry record.

In general, multiplicity arises when several hypotheses or outcomes are tested and the chance of at least one false-positive result can increase if each test is interpreted separately. Statistical plans may address this through a prespecified hierarchy or adjustment, among other approaches. The registry does not report whether any multiplicity procedure was planned or used. Because no secondary results are posted, there is no basis to describe the results of additional endpoints or to determine how they might relate to the primary analysis.

The outcome-specific counts are n of 3 for NMES and n of 5 for transcutaneous electrical stimulation, while total enrollment is recorded as 15. The registry does not explain how these figures relate, identify the analysis population, or state how many enrolled participants had a usable primary outcome. It does not report exclusions, withdrawal details, or reasons for missing outcome data. It is therefore not possible to identify the analysis as intention-to-treat, per-protocol, or another named population from the registry record.

In general, missing outcome data can affect interpretation if the availability of measurements is related to participant characteristics or outcomes. Methods for addressing missingness depend on the data and assumptions; none are described in the posted record. The difference between enrollment and outcome-specific counts should not be attributed to any particular cause without documentation. The record also does not report sensitivity analyses for missing data or comparisons between participants with and without outcome measurements.

The registry gives a primary completion date and a terminated status, but does not state whether termination affected outcome collection, the analysis set, or planned testing. It does not report interim analyses, stopping rules, or any changes to the analysis plan. Those omissions leave the reader unable to assess whether the reported analysis matched an original plan or how missing data and multiplicity were addressed.

13. 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.

The registry lists serious adverse event figures by arm. For the NMES group, 7 are listed as at risk and 0 as affected; for transcutaneous electrical stimulation, 8 are listed as at risk and 0 as affected. The registry also records 0 deaths in each group. These are the posted safety figures and should be read with the event definitions and reporting period in mind, which are not described in the available record.

The safety at-risk counts do not match the outcome-specific counts for the primary endpoint. The registry does not explain that difference, so the safety and efficacy figures should not be assumed to use the same analysis population or observation period. The record lists no top serious-event terms. This indicates that no terms are listed in that field; it does not provide further detail about event ascertainment or reporting.

In general, zero reported events do not establish that an intervention has no risk. The interpretation of safety counts depends on the number of people observed, duration of observation, event definitions, completeness of reporting, and study design. The registry’s safety figures alone do not allow a precise comparison of risk between groups, and no safety effect estimate or confidence interval is reported.

The study’s status is terminated, but the record does not state whether termination affected safety follow-up or reporting. The registry does not provide additional details about non-serious events in this summary. These figures describe what is recorded, not a comprehensive determination of safety.

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

The posted results describe a small randomized study of NMES compared with transcutaneous electrical stimulation in people with heart failure. For the primary outcome, the registry reports group means, standard deviations, and outcome-specific counts, along with a two-sided t-test p-value of 0.22. The record does not report a between-group effect estimate or confidence interval. Accordingly, the data can be described, but the magnitude and precision of the comparison are not fully presented.

The p-value should not be interpreted as a probability that one intervention is better or worse, nor as proof that the groups are equivalent. In general, absence of a small p-value does not establish that there is no meaningful effect; an imprecise estimate can be compatible with a range of possibilities. Here, the absence of a posted contrast estimate and confidence interval prevents direct evaluation of the range of effects compatible with the analysis.

The registry’s group summaries are based on n of 3 and n of 5 for the endpoint, while enrollment is recorded as 15. The record does not explain the relationship between these numbers, identify the analysis population, or describe missing-data handling. The registry status is terminated, without a stated reason. These features constrain interpretation and make it inappropriate to generalize the summaries as precise estimates for a wider population.

The primary endpoint is a walking test intended to estimate everyday activity capacity and measure exercise capacity. It does not by itself establish effects on quality of life, symptoms, hospitalization, mortality, or other outcomes discussed in the registry background. No secondary outcomes are posted. The reported safety entries list zero serious adverse events and zero deaths in each arm, but the record does not provide enough detail to infer that risks are absent or to compare safety precisely.

The result therefore supports a cautious account of the available registry entries: group-level 6 Minute Walk Test summaries and a reported t-test are recorded, while key information about the contrast, precision, analysis population, missing data, and termination is not. It does not establish a definitive treatment effect or justify conclusions beyond the outcome and study record described.

15. Why This Trial Matters Statistically

This study illustrates why a group mean and a p-value are not a complete account of a clinical comparison. The registry reports the mean and standard deviation in each arm and a two-sided t-test result, but does not report the between-arm contrast or its confidence interval. Those missing quantities matter because readers need both an estimate of the size of a difference and an indication of its precision to interpret a continuous outcome fully.

The outcome-specific counts are small, and the standard deviations indicate substantial spread in the observations. In general, estimates based on small groups can be sensitive to individual measurements, while uncertainty may remain large. A p-value cannot resolve that uncertainty on its own. The registry’s figures therefore make a useful case for distinguishing a test of compatibility with a null hypothesis from an estimate of the outcome contrast.

The record also distinguishes enrollment from the counts attached to the endpoint. It lists total enrollment as 15, while the primary outcome summaries have n of 3 and n of 5. Without an account of missing outcomes, eligibility, exclusions, or the analysis population, readers cannot determine why the counts differ. Such accounting is important for understanding who contributed to an estimate and whether the analysis reflects the randomized groups as intended.

Finally, the record includes a terminated status but no explanation, and it does not report the full statistical plan, sample-size justification, or missing-data methods. These gaps show why registry status and numerical results require context. Clear reporting of effect estimates, uncertainty, analysis populations, and study conduct would make it easier to assess how far results can be interpreted. The available entries still allow a focused description of the primary outcome and reported test, while setting clear limits on broader conclusions.

16. 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 primary limitation for interpretation is the lack of a reported between-arm effect estimate and confidence interval. The registry provides arm-level means and standard deviations and a p-value, but these do not communicate the magnitude and precision of the comparison as directly as an estimated contrast with an interval. The record does not report the test statistic or further details of the t-test.

The endpoint summaries have outcome-specific counts of n of 3 and n of 5, whereas enrollment is listed as 15. The registry does not reconcile these entries or report the analysis population, participant flow, exclusions, withdrawals, or missing-data methods. As a result, the reasons for the endpoint counts and the representativeness of the analyzed participants are unknown from the record.

The study is marked terminated, but the reason is not reported. The record also does not describe whether termination affected recruitment, follow-up, or planned analyses. Although it records randomization and quadruple masking, details such as sequence generation, allocation concealment, the people masked, and masking success are not reported. The NMES arm description is truncated, limiting access to the full intervention specification.

Only one primary outcome and one analysis are listed, with no secondary outcomes posted. The registry does not report a complete statistical analysis plan, a sample-size justification, interim analyses, stopping rules, multiplicity procedures, or sensitivity analyses. It is consequently not possible to establish from the record whether the reported analysis followed a prespecified plan or how unreported outcomes were handled.

The safety entries list zero serious adverse events and zero deaths in both groups, but do not give event definitions or enough follow-up detail to assess completeness or comparative precision. The record does not supply participant-level data, which would be needed to examine distributions or individual outcome patterns. These limitations are specific to the available study record and constrain conclusions drawn from its posted results.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Building Strength Through Rehabilitation for Heart Failure Patients (BISTRO-STUDY) — NCT03615469.
• Registry record last updated 2023-05-31; status last verified 2023-05.
• Results first posted 2023-05-31.
• 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.

20. Record Summary

BISTRO-STUDY is a randomized, quadruple-masked, parallel study sponsored by Indiana University. The registry lists heart failure as the condition, total enrollment of 15, a start date of 2018-09-06, a primary completion date of 2020-07-01, and a terminated status. The reason for termination is not reported in the registry record.

The primary outcome is change in the 6 Minute Walk Test from baseline to 5-6 months, measured in meters walked. The registry reports means and standard deviations for the NMES and transcutaneous electrical stimulation arms, with outcome-specific counts of n of 3 and n of 5. A two-sided t-test is reported with p = 0.22. No between-arm estimate or confidence interval is reported.

The registry lists one primary outcome, one analysis, and zero secondary outcomes posted. It does not report the analysis population, missing-data methods, sample-size justification, or full statistical plan. Serious adverse event entries list zero affected participants and zero deaths in each arm; further safety details are not reported.