A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction. (NCT03456856), a na phase 4 study. The primary outcome is Change From Baseline in Heart Rate (HR) at Day 57.

2. Clinical Question

3. Trial Design

This was a prospective, open-label, single-arm intervention study of ivabradine in African-American/Black subjects with heart failure and reduced ejection fraction. The registry lists the study as Phase 4, with no allocation and no masking. Because all participants received the study intervention and there was no randomized control arm, the design does not provide a concurrent between-group treatment comparison.

The registry reports enrollment of 30. The study description includes a 7-day screening period, a 57-day open-label treatment period, and a safety follow-up at day 87 or 30 days after the last administration of the investigational product. The starting ivabradine dose was 5 mg twice daily. Investigators had discretion to start at 2.5 mg twice daily for participants with a history of conduction defects or bradycardia that could lead to hemodynamic compromise. The dose was adjusted at Day 15 and at other clinic visits, but the complete dose-adjustment description is not reported in the registry record.

The primary endpoint was change from baseline in heart rate at Day 57. The registry identifies a repeated-measures model for the least-squares mean and says that scheduled visits and baseline heart rate were included as covariates. The analysis used observed data without imputation for missing values. The registry reports a study start date of 2017-09-28, a primary completion date of 2019-04-19, and a completed status. The sample-size justification, detailed statistical analysis plan, and any interim analyses are not reported in the registry record.

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:

Analysis population for the primary outcome, as defined in the registry: Full analysis set which included all enrolled 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.

Population: Full analysis set which included all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Heart Rate (HR) at Day 57, measured over Day1 (baseline), Day 57.

Heart rate is a continuous measure recorded in beats per minute. The primary endpoint focuses on how heart rate at Day 57 differs from the participant’s baseline value. Describing change from baseline makes the endpoint about within-participant change over the study period rather than only the heart rate measured at the final visit.

The registry specifies a least-squares mean from a repeated-measures model, with scheduled visits and baseline heart rate as covariates. General: a least-squares mean is a model-based estimate adjusted for the variables included in the model; it is not necessarily identical to a simple arithmetic average. The registry states that the mean change was compared with -5 beats/min, described as the change observed in the placebo group in the SHIFT study.

The endpoint can describe the average change estimated for the analysis population, while an uncertainty measure indicates how precisely that average is estimated. The registry identifies the dispersion measure as the standard error, but the estimated change and standard error are not reported in the registry record. The result therefore cannot be described as a particular increase, decrease, or degree of precision from the available endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is described as a least-squares mean from a repeated-measures model. The model included scheduled visits and baseline heart rate as covariates. The registry does not report the full model specification, the estimation method, or the assumptions used to assess model fit.

What does a least-squares mean represent?

General: a least-squares mean is a model-based average adjusted for the covariates included in an analysis. In this study, the registry identifies scheduled visits and baseline heart rate as covariates. This approach can account for those specified variables when estimating the mean change. It does not, by itself, eliminate bias from features not included in the model, and it does not create a concurrent control group in a single-arm study.

The endpoint is a continuous measure: change in heart rate, expressed in beats per minute. For a continuous outcome, an average change communicates the central estimated shift across the analysis population. It does not say that every participant changed by that amount. Individual responses may differ, but their distribution is not reported in the registry record.

How should the standard error be read?

The registry identifies the standard error as the measure of dispersion accompanying the least-squares mean. General: a standard error describes the precision of an estimated mean under the statistical model. It is not the standard deviation of individual measurements, and it should not be interpreted as a range containing most participants’ responses. The actual standard error for the primary endpoint is not reported in the registry record.

A confidence interval can help communicate uncertainty around an estimate by giving a range of values compatible with the data and the model at a specified confidence level. General: wider intervals indicate less precision than narrower intervals, all else equal. A confidence interval for the endpoint is not reported in the registry record. The registry also does not report a p-value or another numerical result for the comparison with the reference value.

What is the role of the -5 beats/min reference?

The endpoint description says that mean change from baseline was compared with -5 beats/min, identified as the placebo-group change observed in the SHIFT study. This is an external reference, not an enrolled comparator group in this study. The present study is open-label and single-arm. It therefore does not estimate a randomized, within-study contrast between ivabradine and placebo or another concurrent treatment.

General: external comparisons can be difficult to interpret because differences in study populations, conduct, measurement, or analysis may affect the comparison. The registry record does not provide details sufficient to assess comparability with the external reference. The observed endpoint estimate and the result of its comparison to that reference are also not reported.

What do planning illustrations mean?

General: sample-size calculations describe how many participants might be needed under specified assumptions to detect a target effect with a chosen statistical procedure. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Such illustrations are planning exercises, not observed findings and not evidence of achieved power.

The registry record does not report the study’s own sample-size justification. The design listed for this study is single-arm, whereas the stated planning assumptions describe equal allocation between two arms. Those assumptions should therefore be read as illustrations, not as a description of the trial’s actual allocation or design. Numerical planning results are not reported in the registry record.

General: over-dispersion matters when outcome variability is greater than a model assumes, because standard errors and resulting uncertainty estimates may then be too small. The registry does not report an over-dispersion assessment for this continuous endpoint; this concept should not be taken as a claim that over-dispersion was present. More broadly, the statistical plan does not report model diagnostics, sensitivity analyses, or a rationale for the chosen model.

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("Ivabradine")
n   <- c(30)
m   <- c(-9.5)
sp  <- c(1.7)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Ivabradine  30  -9.500  9.311  -12.977  -6.023

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. It does not report a multiplicity-adjustment procedure or explain whether any other planned outcomes or analyses were considered when interpreting the primary endpoint. The number of listed measures alone does not establish whether multiplicity was addressed in a broader analysis plan.

For the primary endpoint, the registry says the summary is based on observed data and that no imputation was used for missing values. General: imputation is a way of filling in missing observations using an explicit statistical method. An analysis without imputation uses the available observed values for the stated summary, but the implications depend on why data are missing and how much is missing. The number of participants with observed Day 57 heart-rate data and the amount or pattern of missing data are not reported in the registry record.

The analysis population is described as the full analysis set, including all enrolled participants. This definition identifies the intended population for the analysis, but the registry does not report the participant count contributing to the primary endpoint estimate. The estimate itself, its standard error, and any confidence interval or p-value are not reported in the registry record.

The registry does not report a detailed missing-data strategy beyond stating that no imputation was used for the primary summary. It also does not report sensitivity analyses to evaluate how missing measurements might affect the endpoint. The effect of missing data therefore cannot be assessed from the available record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (3.3%).

The registry reports one serious adverse event among 30 participants at risk and seven other adverse events among 30 participants at risk. It reports no deaths. Dehydration is listed among the serious adverse event terms at 3.3%. These are the safety figures reported for the ivabradine group.

General: an adverse-event count describes events recorded in a study population; it does not, by itself, establish that the study intervention caused an event. The registry figures do not include a concurrent control group for estimating whether event frequency differed from another treatment or from no treatment. The record also does not provide event-level details, timing, or a full account of how serious events were classified.

The figures should be read as safety observations from this single-arm study, not as comparative risk estimates. The registry does not report further detail about the seven other adverse events or the one serious adverse event beyond the listed information. These counts do not support a conclusion about safety relative to another intervention.

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

The registry record documents a prospective, open-label, single-arm study of ivabradine in African-American/Black subjects with heart failure and reduced ejection fraction. It identifies change from baseline in heart rate at Day 57 as the primary endpoint and describes a repeated-measures model for estimating the least-squares mean. It also reports safety-event counts and states that the endpoint summary used observed data without imputation.

Those design and methods details do not supply the primary outcome result. The estimated heart-rate change, standard error, confidence interval, and comparison result are not reported in the registry record. Consequently, the available information does not establish the direction, magnitude, or precision of the endpoint estimate. It also does not allow a direct assessment of the result against the -5 beats/min external reference.

General: a single-arm before-and-after endpoint can describe change among participants over time, but it does not isolate the effect of an intervention from other explanations for change. Without a concurrent control group, the study does not provide a randomized treatment contrast. The external SHIFT placebo-group value is cited as a reference, but it is not a control arm enrolled in this study.

The safety counts describe events recorded among participants in the ivabradine group. They do not show whether the event frequency would have been different under another treatment. The registry reports one serious adverse event, seven other adverse events, and no deaths; dehydration is listed as a serious adverse event term at 3.3%. These figures should not be interpreted as proof of causation or as a comparative safety result.

Overall, the record supports a description of the study’s design, endpoint, analysis population, and reported safety counts. It does not report enough outcome information to characterize the primary result or its statistical uncertainty. Sample-size planning illustrations, if considered, are hypothetical calculations and not observed treatment findings.

14. Why This Trial Matters Statistically

This study is statistically notable for focusing on African-American/Black subjects with heart failure and reduced ejection fraction and for specifying heart-rate change as its primary endpoint. Its single-arm, open-label design makes the type of inference especially important: the endpoint can describe change over time in the enrolled participants, but it does not supply a randomized comparison with a concurrent control group.

The endpoint description also illustrates the distinction between an external reference and a trial comparator. The -5 beats/min value is described as a placebo-group change from the SHIFT study. That reference is not a group enrolled in this study, so it cannot be treated as a like-for-like control generated by the current trial.

The specified repeated-measures model and least-squares mean indicate an adjusted, model-based approach to the continuous endpoint. The registry identifies baseline heart rate and scheduled visits as covariates, and says that the summary uses observed data without imputation. These details help readers understand the intended analysis, while the absence of the numerical endpoint result prevents evaluation of its magnitude and precision.

Finally, the record distinguishes a primary endpoint analysis from safety-event reporting. The reported adverse-event counts are descriptive observations, not comparative rates. Taken together, the design and reporting make clear why estimates, uncertainty measures, missing-data information, and appropriate comparators are central to interpreting clinical trial evidence.

15. 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 most immediate limitation for interpreting the reported study is that the primary endpoint result is not reported in the registry record. The least-squares mean change, standard error, confidence interval, and comparison result are unavailable, so the magnitude and precision of the primary outcome cannot be assessed from the registry entries.

The study was open-label and single-arm, with no concurrent control group. Change from baseline can be described, but the design does not support a randomized comparison with another treatment. The -5 beats/min reference comes from the placebo group in the SHIFT study and is not a control arm in this trial. The registry record does not provide enough information to assess how comparable that external reference is to the study participants and conduct.

The registry says that the endpoint summary was based on observed data and that no imputation was used. It does not report the number of participants contributing Day 57 measurements, the amount or pattern of missing endpoint data, or sensitivity analyses for missingness. The effect of missing data on the result therefore cannot be assessed.

The full analysis set is described as including all enrolled participants, but the endpoint estimate is not reported. The record also does not report the study’s sample-size justification, detailed statistical analysis plan, interim analyses, model diagnostics, or a full dose-adjustment description. The safety figures are limited to the reported counts and listed serious adverse event term; they do not provide a concurrent comparative assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction. — NCT03456856.
• Registry record last updated 2021-10-28; status last verified 2021-10.
• Results first posted 2020-04-07.
• 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.

19. Record Summary

The registry record describes a completed Phase 4, prospective, open-label, single-arm study of ivabradine in African-American/Black subjects with heart failure and reduced ejection fraction. Enrollment was 30. The study included a 7-day screening period, a 57-day treatment period, and safety follow-up at day 87 or 30 days after the last administration.

The primary endpoint was change from baseline in heart rate at Day 57, analyzed as a least-squares mean from a repeated-measures model. The model included scheduled visits and baseline heart rate; the summary used observed data without imputation. The endpoint estimate and its uncertainty are not reported in the registry record.

The registry reports one serious adverse event, seven other adverse events, and no deaths. Dehydration is listed among the serious adverse event terms at 3.3%. The study start date was 2017-09-28, the primary completion date was 2019-04-19, and the status is completed.