This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic (NCT03730961), a randomized phase 2 study. The primary outcome is 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03730961 |
| Phase | Phase 2 |
| Condition | Cardiac Failure, Myocardial Failure, Congestive Heart Failure |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 23 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
The study asks whether 4-hour urinary output after a 40 mg intravenous furosemide bolus differs when participants with heart failure and reduced heart function receive BMS-986231 rather than placebo. Both conditions include a standard dose of loop diuretic. The primary endpoint description specifies that the intended comparison concerns the absolute difference in total urinary volume and the percent change from placebo.
The registry describes a randomized, double-blind, placebo-controlled crossover Phase 2 study. Participants received the BMS-986231-plus-diuretic and placebo-plus-diuretic treatment conditions in different sequences. In one sequence, placebo was given in period 1 and drug in period 2; in the other, drug was given in period 1 and placebo in period 2. The infusions lasted 8 hours, with a 7-28 day wash-out period between them.
The clinical question is therefore about the urinary-output response under these treatment conditions, not about long-term clinical outcomes. Other listed measures include urinary and plasma furosemide concentrations, urinary sodium and potassium measures, clinically relevant hypotension, adverse events, and abnormal clinical laboratory values. These outcomes provide additional descriptions of drug exposure, response, and safety; their results are not reported in the registry record.
The primary outcome has several categories or time points and is not reduced to one comparison in the registry record. Numerical estimates for urinary output, their uncertainty, and a direct statistical test are not reported in the registry record. The clinical question can be identified from the protocol description, but the posted results do not establish the size or precision of the treatment contrast.
3. Trial Design
This was a randomized, double-blind, placebo-controlled, crossover Phase 2 study sponsored by Bristol-Myers Squibb. The registry lists an enrollment of 23 and describes participants with heart failure and impaired systolic function, also referred to as HFrEF in the outcome descriptions. The study is marked completed. Its recorded start date is 2019-01-17, and its primary completion date is 2019-12-11.
The crossover design assigned participants to one of the listed treatment sequences. One sequence received placebo in period 1 and BMS-986231 in period 2; the other received BMS-986231 in period 1 and placebo in period 2. Each treatment condition involved an 8-hour continuous infusion, and the record describes a 7-28 day wash-out period. Furosemide was given as a 40 mg bolus for the primary urinary-output assessment. The registry also lists furosemide and placebo as interventions.
In a crossover study, each participant can contribute observations under more than one treatment condition. General statistical context: this can allow a within-participant comparison, but the analysis needs to account for the paired structure and may need to consider period and sequence effects. The statistical model actually used, including whether it accounted for those features, is not reported in the registry record.
The masking level is listed as quadruple. The registry's primary analysis population is the treated per Protocol set: randomized participants who received both study treatments and completed the study as per protocol. Participants are assigned to the treatment group they received in each period. Details of exclusions, protocol deviations, or the number included in each analysis are not reported in the registry record.
The record lists 16 outcome measures and 11 analyses. It does not report a single consolidated primary comparison, and the numerical primary endpoint results are not reported in the registry record. The design description therefore establishes how treatment conditions were organized, but it does not by itself reveal the estimated treatment effect or the method used to quantify its uncertainty.
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.
Before assignment: 23 participants were randomized/assigned to treatment, and 23 initiated period 1 treatment.
Overall Study
| Stage | Sequence 1 | Sequence 2 |
|---|---|---|
| STARTED | 12 | 11 |
| Period 1 Completion | 12 | 11 |
| Period 2 Completion | 11 | 10 |
| COMPLETED | 12 | 10 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Sequence 1 | Sequence 2 |
|---|---|---|
| Adverse Event | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Treated (per Protocol set) - All randomized participants who were given both study treatments and completed the study as per protocol. Participants are included in the treatment group they received in each 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.
| Characteristic | Unit | Sequence 1 | Sequence 2 | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 11 | 23 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 2 | 8 |
| Age, Categorical: >=65 years | Participants | 6 | 9 | 15 |
| Age, Continuous | Years | 67.7 (SD 8.19) | 69.8 (SD 8.23) | 68.7 (SD 8.10) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 11 | 10 | 21 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 | 11 | 23 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 11 | 11 | 22 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo, measured over 4 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is total urinary output, measured in millilitres, during the 4 hours following an intravenous 40 mg furosemide bolus. It is described as the mean of a continuous measure, with standard deviation as the dispersion measure. The comparison is between participants with HFrEF receiving BMS-986231 infusion and those receiving placebo, with furosemide given in each condition.
General statistical context: urinary volume is a direct, quantitative measure of urine produced during a specified observation period. In a study involving a diuretic, measuring urine output after the dose can characterize the short-term urinary response under the treatment conditions. This endpoint is different from a longer-term clinical outcome: it records a physiological measure over a defined period rather than describing subsequent health status.
The registry states that the endpoint description includes the absolute difference in total volume and percent change from placebo. Those are distinct ways of expressing a treatment contrast: an absolute difference remains in the measurement's units, while a percent change expresses a relative comparison. No numerical estimate for either expression, standard deviation, confidence interval, or significance test is reported in the registry record. The primary outcome has several categories or time points and is not reduced to one comparison in the registry record, so the posted information does not support a single numerical statement about the observed urinary-output contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the treatment question and the intended primary measure, but it does not report a single numerical primary comparison. In particular, the primary outcome has several categories or time points and is not reduced to one comparison in the registry record. No mean urinary-output value, treatment contrast, standard deviation, confidence interval, or p-value is reported in the registry record. The direction, size, and precision of the primary treatment effect therefore cannot be characterized from the posted information.
The endpoint description says the study assessed absolute difference in total urinary volume and percent change from placebo. These descriptions indicate the kinds of contrasts intended, not their observed values. Without the estimates and their uncertainty, it is not possible to assess whether the data are compatible with a small or large effect, or how much uncertainty surrounds the comparison. No conclusion about statistical significance can be drawn from the registry record.
The design is crossover, so observations under the treatment conditions are not necessarily independent. General statistical context: within-participant data can be analyzed using methods that recognize pairing; estimates and standard errors may differ from those produced by treating each period as unrelated. Period, sequence, and carryover considerations can also matter in crossover studies. The analysis method and handling of these considerations are not reported in the registry record, so it is not possible to assess whether or how they affected the primary estimate.
The record lists 16 outcome measures and 11 analyses, including secondary measures of FeNa, FeK, furosemide concentrations, urinary sodium relative to urinary furosemide, hypotension, adverse events, and laboratory values. Numerical results for these outcomes are not reported in the registry record. The existence of multiple outcomes does not indicate which analyses were prespecified as confirmatory or how their interpretation was coordinated.
The safety information includes treatment-specific counts for serious and other adverse events, along with a list of serious-event terms. These counts are descriptive and do not provide, on their own, a causal comparison. The registry does not report the statistical analysis plan, event-level timing, or a formal comparison of safety rates. The record also does not report an account of missing outcome data or an explanation of how incomplete observations were handled.
Planning illustrations, when used, should be understood as hypothetical design calculations rather than evidence about the observed treatment effect or the chance that the study detected an effect. The stated assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These assumptions do not supply the missing primary estimate or establish observed power. The sponsor's own analysis is not available as a consolidated primary comparison in the registry record.
9. Statistical Methods Explained
What does the mean describe?
The primary measure is a continuous quantity: total urine volume in millilitres over the 4-hour period after the furosemide bolus. A mean describes the average measured volume in the analysis population for a treatment condition. The registry lists standard deviation as the measure of dispersion. General statistical context: the standard deviation describes how spread out individual observations are around the mean; it is not the uncertainty of the estimated mean. A confidence interval, if reported, would describe uncertainty around an estimate under the assumptions of the analysis. Neither a numerical mean nor a confidence interval for the primary endpoint is reported in the registry record.
What would a treatment contrast mean?
The endpoint description specifies an absolute difference in total urinary volume and a percent change from placebo. General statistical context: an absolute difference is expressed in the original units, here millilitres, and can be interpreted as a difference in average volume over the measurement period. A percent change expresses the contrast relative to the placebo condition. The two summaries answer related but not identical questions, and their interpretation depends on the estimates and the method used to calculate them. The registry record does not report the numerical values needed to interpret either contrast.
Why does crossover structure matter?
The study used a crossover model, with participants assigned to sequences that received placebo and BMS-986231 in different periods. General statistical context: because a participant may contribute measurements under both conditions, the observations can be correlated. A paired analysis can use the within-participant comparison, while an analysis that ignores pairing may misrepresent the uncertainty. Period effects, sequence effects, and persistence of a treatment effect into a later period can also be relevant considerations. The registry describes a 7-28 day wash-out period but does not report the statistical model, tests for these effects, or how any such effects were handled.
The description of the primary population also matters. It is the treated per Protocol set: randomized participants who received both study treatments and completed the study as per protocol. Participants are included in the treatment group received in each period. General statistical context: a per-protocol analysis can differ from an analysis that retains all randomized participants, because the analysis population is defined by treatment receipt and completion requirements. The registry does not report participant-level disposition or the number contributing primary endpoint data in each period.
What can significance testing establish?
General statistical context: a significance test evaluates how compatible the observed data are with a specified null hypothesis under the test's assumptions. A p-value does not measure the probability that a treatment effect is true, and it does not describe the size or clinical importance of an effect. An estimate and its confidence interval are usually more informative about magnitude and precision. No primary p-value, confidence interval, or test specification is reported in the registry record. It is therefore not possible to reconstruct or interpret a primary significance test from the information available.
How should multiple outcomes be considered?
The record lists 16 outcome measures and 11 analyses. General statistical context: examining multiple outcomes or multiple comparisons can increase the chance that at least one result appears notable by chance if no adjustment or prespecified hierarchy is used. Methods for addressing this include adjusting significance thresholds or defining a sequence for testing, but the appropriate approach depends on the study's aims and analysis plan. The registry record does not report a multiplicity procedure, an outcome hierarchy, or which analyses were designated confirmatory. The number of listed measures alone cannot establish how multiplicity was handled.
What do planning calculations say?
The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. General statistical context: planning calculations estimate the sample size needed under assumptions about the target effect, variability, allocation, and analysis. They are not a measure of the probability that a completed study detected an effect. Such calculations are planning illustrations, not observed power. The registry record does not report a specific primary outcome estimate that can be used to judge the precision of the observed treatment comparison, nor does it establish that these illustrations were the trial's original design justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 16 outcome measures and 11 analyses. Outcomes include the primary urinary-output measure and secondary measures of FeNa, FeK, furosemide urinary and plasma concentrations, urinary sodium relative to urinary furosemide, clinically relevant hypotension, adverse events, and abnormal clinical laboratory values. Listing multiple outcomes raises a question about how their results were intended to be interpreted together. A multiplicity adjustment, testing hierarchy, or other prespecified strategy is not reported in the registry record.
The primary outcome has several categories or time points and is not reduced to one comparison in the registry record. This limits the ability to identify a single primary estimate for interpretation. The registry does not report a numerical result for the primary outcome, a confidence interval, or a p-value. It also does not state whether any analyses were exploratory or confirmatory.
The analysis population is described as the treated per Protocol set: randomized participants who received both study treatments and completed the study as per protocol. Participants are included in the treatment group they received in each period. This description does not show how many participants contributed data to each analysis or whether any randomized participants were excluded. The handling of missing outcome measurements, incomplete periods, or protocol deviations is not reported in the registry record.
General statistical context: missing observations can affect both the estimate and its precision, particularly when the reason for missingness is related to treatment or response. Assessing this usually requires information about the amount and pattern of missingness, the analysis method, and any sensitivity analyses. Those details are not reported in the registry record. No assumptions about missing data or multiplicity should be inferred from the listed analysis population or outcome count.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BMS-986231 | 1 | 23 | 4.3% |
| Placebo | 2 | 23 | 8.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BMS-986231 | 0 of 23 |
| Placebo | 0 of 23 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BMS-986231 | 6 of 23 |
| Placebo | 3 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | BMS-986231 | Placebo |
|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 1 of 23 | 0 of 23 |
| Lower respiratory tract infection | Infections and infestations | 1 of 23 | 0 of 23 |
| Acute kidney injury | Renal and urinary disorders | 0 of 23 | 1 of 23 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 0 of 23 | 1 of 23 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 23 | 1 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BMS-986231 | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 3 of 23 | 1 of 23 |
| Hypotension | Vascular disorders | 3 of 23 | 0 of 23 |
| Lower respiratory tract infection | Infections and infestations | 0 of 23 | 2 of 23 |
| Dizziness | Nervous system disorders | 2 of 23 | 0 of 23 |
Serious events with the highest arm-level rate: myocardial infarction (4.3%), lower respiratory tract infection (4.3%), acute kidney injury (4.3%), chronic obstructive pulmonary disease (4.3%), dyspnoea (4.3%).
The registry lists serious adverse event figures separately for BMS-986231 and placebo. For each treatment, 23 participants are listed at risk. The record lists 1 serious adverse event for BMS-986231 and 2 for placebo. It lists 6 other adverse events for BMS-986231 and 3 for placebo. Deaths are listed as 0 in each treatment group. These are descriptive counts; the registry does not report a formal statistical comparison of the figures.
The serious-event terms listed include myocardial infarction, lower respiratory tract infection, acute kidney injury, chronic obstructive pulmonary disease, and dyspnoea, each reported as 4.3%. These entries identify terms appearing in the registry's serious-event listing; they do not establish that treatment caused an event. The record does not provide the event-level timing, participant-level descriptions, or a causal assessment for these terms.
Because this was a crossover study, participants received both treatment conditions in different periods. The treatment-specific counts should therefore be read as registry entries for the treatment groups, not as evidence that the groups represent unrelated participants. The record does not give enough detail to determine event overlap across periods or to make a participant-level comparison. The figures describe the recorded safety outcomes; they do not establish comparative safety or exclude uncommon harms.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study examined short-term urinary output after a 40 mg furosemide bolus under BMS-986231 and placebo infusion conditions in participants with heart failure and impaired systolic function. Its randomized, double-blind crossover design provides the framework for comparing those conditions. The record also describes the treatment sequences, the 8-hour infusions, and the 7-28 day wash-out period.
The posted information does not, however, give a single numerical primary comparison. The primary outcome has several categories or time points and is not reduced to one comparison in the registry record. Mean urinary output, the absolute difference, percent change from placebo, standard deviation, confidence interval, and p-value are not reported in the registry record. As a result, the magnitude and precision of the primary treatment contrast cannot be assessed from the posted results.
The listed secondary measures broaden the outcomes considered, but their numerical results are not reported in the registry record. Their presence does not establish whether they were analyzed as confirmatory outcomes, how multiple comparisons were handled, or what the findings were. The serious and other adverse-event counts provide descriptive safety information, but they do not by themselves establish a causal treatment effect or a formal difference between conditions.
General statistical context: an estimate is most informative when considered alongside its uncertainty and the analysis assumptions. In a crossover study, interpretation also depends on how within-participant correlation, period, and sequence are handled. The record does not provide the consolidated analysis or methods needed to evaluate these aspects. Accordingly, the design and endpoint can be described, but no conclusion about the direction, size, statistical significance, or clinical importance of the primary effect can be drawn from the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because the crossover design compares treatment conditions within a sequence of periods rather than describing only a parallel-group assignment. General statistical context: repeated measurements from the same participant are related, so the analysis needs to respect that structure. The registry describes the sequences and wash-out period, but the model used to analyze the primary endpoint is not reported in the registry record. That distinction matters when evaluating how an estimated contrast and its uncertainty were obtained.
The primary outcome is a continuous measure with a defined observation window: urinary volume during the 4 hours after a furosemide bolus. The registry describes both an absolute difference and percent change from placebo as intended summaries. These forms can make a contrast interpretable in different ways, but the numerical estimates and their uncertainty are not reported in the registry record. The absence of a consolidated comparison prevents a statistical reading of the primary result.
The record also lists 16 outcome measures and 11 analyses. General statistical context: when several outcomes are examined, a clear analysis hierarchy or multiplicity strategy helps readers distinguish primary evidence from secondary or exploratory findings. Such a strategy is not reported in the registry record. The listed outcomes therefore show the breadth of measurement, but not how the study prioritized or adjusted analyses.
Finally, the described treated per Protocol set makes the analysis population important to interpretation. It includes randomized participants who received both treatments and completed the study as per protocol, with participants grouped by treatment received in each period. The number analyzed and the handling of missing measurements are not reported in the registry record. These features illustrate why reporting the analysis population, statistical model, estimates, and uncertainty is essential for understanding a clinical trial comparison.
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.
A central limitation of the registry record is that the primary outcome is not reduced to a single comparison. Although the endpoint description identifies urinary output after a 40 mg furosemide bolus and specifies absolute and relative contrasts, numerical estimates and uncertainty measures are not reported in the registry record. The magnitude and precision of the primary result therefore cannot be evaluated.
The statistical methods are also incompletely described. The study is a crossover trial with treatment sequences and a 7-28 day wash-out period, but the model used for analysis and the handling of within-participant correlation, period, sequence, or possible carryover effects are not reported in the registry record. No method for addressing multiplicity is reported despite the listing of 16 outcome measures and 11 analyses.
The analysis population is defined as treated per Protocol, but the number contributing data to the primary analysis and the reasons for any exclusions are not reported. Missing-data methods, sensitivity analyses, and the handling of incomplete treatment periods are also not reported in the registry record. These omissions limit assessment of how the analysis population may relate to the randomized study population.
The safety information is presented as event counts and serious-event terms, without event-level timing or a formal comparative analysis. The registry does not report a causal assessment for the listed serious events. These limitations mean that the recorded safety counts can be described, but cannot establish comparative safety. More broadly, the available record supports description of the study design and selected safety figures, not a complete statistical assessment of treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic — NCT03730961.
- Registry record last updated 2021-02-26; status last verified 2021-02.
- Results first posted 2021-01-26.
- 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.
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18. Record Summary
NCT03730961 is a completed randomized, double-blind, placebo-controlled crossover Phase 2 study sponsored by Bristol-Myers Squibb. The registry lists an enrollment of 23 and dates of 2019-01-17 for study start and 2019-12-11 for primary completion. Participants with heart failure and impaired systolic function received BMS-986231 and placebo in different sequences, with furosemide given in both treatment conditions.
The primary endpoint was mean urinary output in millilitres during the 4 hours after a 40 mg furosemide bolus. The infusions were 8 hours, with a 7-28 day wash-out period. The primary outcome has several categories or time points and is not reduced to one comparison in the registry record. Numerical primary estimates, uncertainty measures, and the statistical analysis method are not reported in the registry record.
The record lists 16 outcome measures and 11 analyses. It describes a treated per Protocol analysis population and reports descriptive serious and other adverse-event counts by treatment. The multiplicity strategy and missing-data methods are not reported in the registry record.