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 Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (NCT01685840), a randomized na study. The primary outcome is CV Death or Heart Failure Hospitalization.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01685840 |
| Phase | NA |
| Condition | Heart Failure |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 894 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Duke University |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes a trial in high-risk patients with left ventricular systolic dysfunction and lists heart failure as the condition. It records enrollment of 894 participants. The arm records list 448 participants assigned to usual care and 446 assigned to biomarker-guided care. Further eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
Biomarker-guided care used NT-proBNP results to help clinicians adjust standard heart failure treatments and drug doses. Participants in this group also received standard heart failure treatment. The record describes the biomarker as an aid to treatment decisions, not as a replacement for usual clinical care.
Comparator
The usual-care group received standard heart failure treatment based on the doctor's judgment and current guideline recommendations. The description says treatment would typically include medicines such as beta-blockers, ACE-inhibitors, and diuretics. The registry does not report how treatment choices or changes were standardized across clinicians.
Primary question
The primary objective was to compare a biomarker-guided treatment strategy with usual care in relation to the composite of first heart failure hospitalization or cardiovascular mortality. The primary outcome is recorded over 24 months. The central statistical question is whether the time-to-event comparison indicates a difference between the assigned strategies, and how precisely the estimated relative event rate is measured.
3. Trial Design
This was a randomized, parallel-group trial with no masking reported. The registry lists enrollment of 894 and two arms: usual care, with 448 participants, and biomarker-guided care, with 446 participants. The phase is recorded as NA. The listed sponsor is Duke University.
The intervention group received standard heart failure treatment, with NT-proBNP blood-test results used to help guide treatment adjustments and drug doses. The comparator received standard treatment based on the treating doctor's judgment and guideline recommendations. The record's description of usual care is truncated, so its complete intervention details are not available. The registry does not report the randomization procedure, allocation concealment, treatment adherence, or whether participants crossed between strategies.
The study began in 2012-12, and the primary completion date is 2016-09-20. Its status is TERMINATED. The reason for termination is not reported in the registry record. The primary outcome timeframe is 24 Months. Although all-cause mortality and several other outcomes are listed as secondary outcomes, their measurement schedules and analysis details are not reported in the registry record.
Randomization is intended, in general, to make treatment groups comparable on average, while a parallel design assigns participants to one strategy for the comparison. Because masking is recorded as NONE, the trial was unmasked. The record does not explain whether outcome assessment was masked or how unmasking might have affected care or reporting.
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: 894 participants were randomized
Overall Study
| Stage | Usual Care | Biomarker-Guided Care |
|---|---|---|
| STARTED | 448 | 446 |
| COMPLETED | 119 | 114 |
| NOT COMPLETED | 329 | 332 |
Reasons for not completing this period:
| Reason | Usual Care | Biomarker-Guided Care |
|---|---|---|
| Death | 77 | 66 |
| Lost to Follow-up | 27 | 25 |
| Physician Decision | 3 | 7 |
| Withdrawal by Subject | 14 | 17 |
| Futility | 197 | 200 |
| Had VAD, Dialysis or Transplant | 11 | 17 |
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 | Usual Care | Biomarker-Guided Care | Total |
|---|---|---|---|---|
| Participants analysed | 448 | 446 | 894 | |
| Age, Continuous | years | 62.5 (SD 13.4) | 60.4 (SD 14.3) | 61.5 (SD 13.9) |
| Sex: Female, Male: Female | Participants | 147 | 139 | 286 |
| Sex: Female, Male: Male | Participants | 301 | 307 | 608 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 28 | 30 | 58 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 420 | 416 | 836 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 2 | 3 |
| Race (NIH/OMB): Asian | Participants | 11 | 16 | 27 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 3 | 4 | 7 |
| Race (NIH/OMB): Black or African American | Participants | 155 | 167 | 322 |
| Race (NIH/OMB): White | Participants | 257 | 228 | 485 |
| Race (NIH/OMB): More than one race | Participants | 14 | 13 | 27 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 7 | 16 | 23 |
6. Primary Endpoint
The registry lists the primary outcome as CV Death or Heart Failure Hospitalization, measured over 24 Months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is a composite of first heart failure hospitalization or cardiovascular mortality, recorded as a number of events over 24 months. It brings together a hospitalization outcome and a fatal cardiovascular outcome into one measure. The registry's primary outcome title is “CV Death or Heart Failure Hospitalization,” and its description specifies the first heart failure hospitalization or cardiovascular mortality.
In general, a composite endpoint can capture more than one clinically relevant type of event and can support a time-to-event comparison of when participants experience the outcome. However, a composite result does not show by itself how much each component contributed. The registry lists 164 events in each arm, but does not provide component-specific primary-outcome counts in this record. Therefore, the posted primary comparison cannot establish whether the components had similar or different patterns.
The registry reports a Cox-regression hazard ratio for the comparison. In general, this type of estimate compares the relative event rate over follow-up, rather than simply comparing total event counts at a single time. The record does not report additional details about how the composite was adjudicated, how censoring was handled, or whether participants were analyzed according to their randomized assignment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The arm-level primary outcome records list 164 events for usual care and 164 for biomarker-guided care. The registry's reported comparative analysis is a Cox regression with a hazard ratio of 0.98, a 95% confidence interval from 0.79 to 1.22, and p = 0.88. The interval includes the no-difference value for a hazard ratio. The estimate is close to that value, while the interval also allows for effects in either direction.
A confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. Here, the interval is not narrow enough to identify a precise direction or magnitude of the relative difference. The p-value summarizes how compatible the observed result is with a specified null model under the analysis assumptions; it is not the probability that either treatment strategy is better, nor does it measure the clinical importance of a difference. The registry does not state the decision threshold used for interpreting the p-value.
The equal event counts do not replace the time-to-event analysis. A hazard ratio uses event timing and follow-up information, whereas the arm-level counts alone do not indicate when events occurred or how censoring was handled. No component-specific primary-outcome results are reported, so the composite result cannot be attributed separately to cardiovascular mortality or heart failure hospitalization.
The result is a comparison of assigned care strategies as analyzed in the registry, not a demonstration that all participants received identical treatment within their assigned arm. Details of adherence, treatment changes, and analysis populations are not reported in the registry record. The status is TERMINATED, but the reason for termination is not reported; that status alone does not establish why the study ended or how termination affected the analysis.
Overall, the posted estimate does not show a clear separation in the primary composite outcome, and its confidence interval leaves meaningful uncertainty about the relative effect. That is a statement about the statistical evidence in this record, not a conclusion about the clinical value of either strategy. Interpretation also depends on the design, outcome definitions, completeness of follow-up, and analysis choices, several of which are not reported in the registry record.
9. Statistical Methods Explained
The primary comparison is reported as a Cox regression with a hazard ratio. In general, Cox regression is a time-to-event method: it uses information about when an event occurs and about participants' follow-up, including follow-up that ends before an event is observed. A hazard ratio expresses the relative event rate between groups over time under the model. It is not the same as a difference in the total number of events, a risk ratio, or a comparison of average event counts.
What the hazard ratio describes
The reported hazard ratio is 0.98. In general, a hazard ratio at the no-difference value indicates equal hazards under the model; estimates on either side indicate different relative hazards. The reported estimate is close to the no-difference value, but the confidence interval is needed to understand its precision. The registry does not report whether the proportional-hazards assumption was checked or whether the model included covariate adjustment.
How to read the confidence interval
The reported 95% confidence interval extends from 0.79 to 1.22. In general, a confidence interval represents a range of estimates compatible with the observed data and statistical model at the stated confidence level. It is not a range containing a known true effect with a probability attached to this particular interval. Because the range includes the no-difference value for a hazard ratio, the result is compatible with no relative difference as well as with effects in either direction. The interval's breadth conveys uncertainty; the registry does not report a clinical threshold for an important difference.
What the p-value contributes
The p-value is 0.88. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null hypothesis and model. It does not give the probability that the null hypothesis is true, and it does not quantify the chance that the result is due to random error. A p-value should be read alongside the estimate and confidence interval, not on its own. The registry does not report a prespecified significance threshold or a detailed statistical analysis plan.
Why event counts are not the whole analysis
The posted arm records each list 164 primary events. Those counts do not convey event timing, duration of observation, or censoring. A time-to-event model can incorporate those features, which is why its hazard ratio need not be inferred from counts alone. The primary endpoint is a composite, and the record does not separate the event counts by component. It also does not report Kaplan-Meier estimates, median follow-up, or details of censoring.
Other statistical considerations
In general, over-dispersion matters when count outcomes vary more than a simple count model expects; ignoring it can make uncertainty estimates too small. That concept does not establish that over-dispersion occurred in this trial. The primary comparative result is reported as a Cox model, and the registry does not describe a count model or report a dispersion estimate for this outcome.
The record lists 18 outcome measures, 54 analyses, and 17 posted secondary outcomes. In general, testing many outcomes or conducting many analyses raises a multiplicity concern: the more comparisons considered, the greater the chance that some may appear notable by chance. The registry does not report a multiplicity adjustment strategy, hierarchy of outcomes, or which analyses were prespecified. The count of analyses alone does not show that the primary result is biased; it does mean that secondary findings require context about selection and statistical planning.
Planning sample sizes are not outcome evidence. In general, such calculations depend on assumptions about the effect to detect, allocation, and statistical model. No numeric sample-size planning results or trial-specific justification are reported in the registry record. The registry also does not report an interim-analysis plan, stopping boundary, missing-data approach, or analysis-population definition.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Regression, Cox | Hazard Ratio (HR) 0.98 | 0.79 to 1.22 | 0.880 |
The registry reports the sponsor's comparative analysis as a Cox regression: hazard ratio 0.98, 95% confidence interval 0.79 to 1.22, and p = 0.88. The registry record does not include a separate recalculated hazard ratio for this primary comparison. A separate recalculated result therefore cannot be used to check or replace the reported model estimate.
The arm records show 164 events in each group, but those totals do not reproduce a time-to-event analysis. Recalculation from aggregate counts would not account for event timing, censoring, or any model adjustments. The analysis details needed to make an independent Cox-regression estimate are not reported in the registry record.
The registry does not report the covariates, model diagnostics, or assumptions used for the sponsor's Cox analysis. The reported estimate should therefore be read as the available comparative analysis, with the confidence interval and p-value interpreted in that context. No discrepancy between a sponsor analysis and a recalculated comparison is reported for this result.
11. Multiplicity, Missing Data and Analysis Populations
The record lists 18 outcome measures, 54 analyses, and 17 posted secondary outcomes. These counts indicate a broad set of outcomes and analyses, but do not describe how the analyses were selected or prioritized. The registry does not report whether the secondary outcomes were prespecified in a hierarchy, whether multiplicity was addressed, or whether the primary comparison was protected from other testing.
In general, multiplicity arises when researchers make many statistical comparisons. Without an appropriate plan, repeated testing can increase the chance of at least one apparently notable result arising by chance. This is a reason to interpret secondary findings in the context of the trial's analysis plan; it is not evidence that a particular reported result is false. The registry record does not provide enough detail to assess how multiplicity may have been handled.
Missing-data methods are not reported in the registry record. The record does not describe losses to follow-up, the amount or pattern of missing outcome information, imputation, or sensitivity analyses. Those details matter because incomplete observation can affect estimates, particularly for time-to-event outcomes when censoring is related to participants' prognosis or treatment experience.
Analysis populations are also not reported in the registry record. It is not stated whether the primary analysis followed intention-to-treat, per-protocol, or another approach. The randomized arm counts do not by themselves establish which participants were included in each analysis. The record does not report adherence or crossover information, either.
The registry gives a primary completion date and a TERMINATED status, but does not report the reason for termination or whether a prespecified stopping rule was used. It also does not report interim analyses. Without those details, the timing and conduct of the final analysis cannot be fully assessed.
12. 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 |
|---|---|---|---|
| Usual Care | 36 | 448 | 8.0% |
| Biomarker-Guided Care | 51 | 446 | 11.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Usual Care | 77 of 448 |
| Biomarker-Guided Care | 66 of 446 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Usual Care | 157 of 448 |
| Biomarker-Guided Care | 178 of 446 |
Most frequent serious adverse event terms
| Event term | Organ system | Usual Care | Biomarker-Guided Care |
|---|---|---|---|
| Other Adverse Events | Investigations | 19 of 448 | 17 of 446 |
| Worsening renal function | Renal and urinary disorders | 9 of 448 | 16 of 446 |
| Hyperkalemia | Blood and lymphatic system disorders | 6 of 448 | 11 of 446 |
| Symptomatic Hypotension | Cardiac disorders | 2 of 448 | 7 of 446 |
| Symptomatic Bradycardia | Cardiac disorders | 0 of 448 | 0 of 446 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Usual Care | Biomarker-Guided Care |
|---|---|---|---|
| Worsening renal function | Renal and urinary disorders | 83 of 448 | 91 of 446 |
| Symptomatic Hypotension | Cardiac disorders | 30 of 448 | 37 of 446 |
| Hyperkalemia | Blood and lymphatic system disorders | 22 of 448 | 30 of 446 |
| Other Adverse Events | Investigations | 19 of 448 | 18 of 446 |
| Symptomatic Bradycardia | Cardiac disorders | 3 of 448 | 2 of 446 |
Serious events with the highest arm-level rate: other adverse events (4.2%), worsening renal function (3.6%), hyperkalemia (2.5%), symptomatic hypotension (1.6%), symptomatic bradycardia (0.0%).
The adverse-event record lists serious adverse events affecting 36 participants in usual care and 51 in biomarker-guided care. It lists other adverse events affecting 157 and 178 participants, respectively. Death counts are listed as 77 and 66. These are registry-recorded counts; the record does not provide event timing, participant-level overlap across categories, or a comparative statistical analysis for these figures.
The registry lists the following serious adverse-event terms and percentages: Other Adverse Events, 4.2%; Worsening renal function, 3.6%; Hyperkalemia, 2.5%; Symptomatic Hypotension, 1.6%; and Symptomatic Bradycardia, 0.0%. The record does not clarify in this summary how these percentages were calculated or whether the listed terms refer to one arm or both arms. They should not be treated as directly comparable between treatment groups without that context.
Counts alone do not establish a treatment-related cause or show whether an observed difference is statistically reliable. The registry does not report severity grading beyond the serious-versus-other classification, attribution to treatment, exposure-adjusted rates, or tests comparing adverse events between groups. The death counts in the adverse-event record should not be assumed to be the same endpoint definition as all-cause mortality listed among secondary outcomes.
13. What the Result Does, and Does Not, Mean
The primary result is a Cox-regression hazard ratio of 0.98, with a 95% confidence interval from 0.79 to 1.22 and p = 0.88. The arm records list 164 primary events in each group. These results do not show a clear difference in the composite of first heart failure hospitalization or cardiovascular mortality over 24 months. The confidence interval also indicates that the estimate is not precise enough to rule out effects in either direction.
This is not proof that the two strategies are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether differences are small enough to fall within that margin. The registry does not report an equivalence or non-inferiority design or a margin. Nor does a non-significant-looking result establish that no clinically meaningful difference exists.
The result applies to the registered comparison and endpoint, not to every outcome or every feature of heart failure care. The endpoint combines cardiovascular mortality with first heart failure hospitalization, and component-specific primary results are not reported. Secondary outcomes are listed, but their results and analysis details are not included in the registry record used for this interpretation.
The comparison also does not isolate the effect of the NT-proBNP test from all other aspects of care. The intervention was a strategy in which clinicians used the test results to help adjust standard treatments. Information about actual treatment changes, adherence, and the analysis population is not reported in the registry record.
Finally, the registry status is TERMINATED, but the reason is not reported. The status alone does not explain the trial's conduct or the meaning of its statistical result. The appropriate reading is therefore bounded: the posted primary analysis is compatible with no relative difference, but it leaves uncertainty and does not answer every clinical or statistical question raised by the trial.
14. Why This Trial Matters Statistically
This trial is statistically informative because it tests a treatment strategy rather than a single drug against no treatment. The biomarker-guided group received standard heart failure treatments, with NT-proBNP results used to help adjust treatment. The comparator also received standard care. This makes the primary question one of whether adding biomarker information to clinical decision-making changes outcomes compared with usual care.
The primary endpoint combines first heart failure hospitalization and cardiovascular mortality and is analyzed using a time-to-event method. That combination makes it important to distinguish the overall composite result from the contributions of its components. The registry gives the overall comparison but does not report component-specific primary outcomes in this record.
The reported hazard ratio is close to the no-difference value, while its confidence interval spans values on both sides of that value. This illustrates why statistical interpretation should consider both the point estimate and uncertainty, rather than relying only on event counts or a p-value. The listed equal event counts cannot convey event timing or follow-up patterns used by the Cox analysis.
The record also highlights the limits of registry-level interpretation. It lists many outcome measures and analyses but does not describe multiplicity handling, missing-data methods, or analysis populations. Those omissions do not negate the reported result, but they limit assessment of how robustly the analysis was planned and conducted. For clinical researchers, the case underscores the value of clear outcome definitions and transparent reporting of analysis decisions alongside effect estimates.
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.
Several trial-specific details needed for a fuller assessment are not reported in the registry record. The reason for the TERMINATED status is not given. The record also does not describe the randomization procedure, allocation concealment, baseline characteristics, or whether outcome assessment was masked. Masking is recorded as NONE, but the record does not clarify which trial roles were unmasked.
The primary comparison is reported as a Cox regression, but the model specification is not described. Covariate adjustment, proportional-hazards assessment, censoring rules, and handling of participants with incomplete follow-up are not reported. The record does not define the analysis population or describe adherence, treatment crossover, or treatment changes beyond the general intervention description.
The primary composite is defined as first heart failure hospitalization or cardiovascular mortality, but separate component results are not reported in the primary outcome record. This prevents assessment of whether the overall result reflects similar patterns across components. Details of event adjudication and the timing of events are also not reported.
The registry lists 18 outcome measures, 54 analyses, and 17 posted secondary outcomes, but does not report a prespecified outcome hierarchy or multiplicity strategy. The statistical analysis plan, sample-size justification, interim analyses, and any stopping rules are not reported in the registry record. These gaps limit assessment of the planned-versus-reported analysis and the treatment of multiple comparisons.
The safety summary gives counts and selected percentages but does not provide arm-specific percentages for the listed terms, attribution, timing, or comparative tests. The record's description of usual care is incomplete. Together, these limitations mean the registered result can be described, but not fully reconstructed or independently validated from the aggregate information in the record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment — NCT01685840.
- Registry record last updated 2017-12-12; status last verified 2017-11.
- Results first posted 2017-12-12.
- 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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19. Record Summary
The registry describes a randomized, parallel-group, unmasked trial sponsored by Duke University, with enrollment of 894 and a TERMINATED status. It compares usual heart failure care with standard care guided in part by NT-proBNP results. The primary endpoint is first heart failure hospitalization or cardiovascular mortality over 24 months.
The arm records list 164 primary events in each group. The reported Cox-regression hazard ratio is 0.98, with a 95% confidence interval from 0.79 to 1.22 and p = 0.88. The estimate does not show a clear difference, and the interval leaves uncertainty about the relative effect.
The registry does not report the reason for termination, the statistical analysis plan, missing-data methods, analysis populations, or multiplicity handling. Component-specific primary results are also not reported in the registry record.