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 Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure (NCT02151383), a na phase 2 study. The primary outcome is Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02151383 |
| Phase | Phase 2 |
| Condition | Acute Heart Failure |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric patients from birth to <18 years of age hospitalized with acute heart failure. The registry record reports enrollment of 12. Its primary safety population is described as enrolled subjects exposed to study drug who had at least one post-baseline safety assessment.
Intervention
Intravenous serelaxin added to standard therapy for acute heart failure. The arm description says treatment continued for a total of 48 hours. The study was described as dose escalation.
Comparator
There was no randomized comparator: the study is recorded as single-group, with allocation listed as NA. Standard care was background therapy, not a separately assigned control arm. The cohorts should not be read as like-for-like treatment and control groups.
Primary question
The primary outcome counts patients with treatment-emergent adverse events, serious adverse events and death. The stated follow-up runs through 28 days plus 30 days of serious-adverse-event follow-up after study completion or discontinuation. The primary question is therefore about observed safety events during the specified follow-up, not a randomized estimate of treatment benefit.
This question is narrower than asking whether serelaxin improves acute heart failure outcomes. The record identifies safety, tolerability and pharmacokinetics as the study purpose, and lists changes in cardiovascular pressure and oxygen-saturation measures among secondary outcomes. It does not provide a randomized comparison that would isolate the effect of serelaxin from background care, changes over time, or the clinical circumstances of the participants.
3. Trial Design
This was a Phase 2, multicenter, open-label, dose-escalation study of serelaxin in pediatric patients hospitalized with acute heart failure. The registry lists a single-group model, no masking, and allocation as NA. Serelaxin was administered intravenously on top of standard therapy, with the arm description specifying a total treatment duration of 48 hours. The record reports enrollment of 12.
The stated study purpose was to evaluate safety, tolerability and pharmacokinetics. The primary outcome counts patients with treatment-emergent adverse events, serious adverse events and death. Its stated follow-up extends through 28 days plus 30 days of serious-adverse-event follow-up after completion or discontinuation. The primary safety population is described as enrolled subjects who were exposed to study drug, regardless of exposure, and had at least one post-baseline safety assessment.
Secondary outcomes include changes from baseline in mean left arterial pressure, pulmonary artery pressure and central venous pressure, with measures specified for low- and high-dose groups. Baseline and change from baseline in central venous pressure and arterial oxygen saturation are also listed. These outcomes describe measurements during treatment or follow-up; their presence in the registry does not establish that results were reported.
The record lists a start date of 2014-09-05, a primary completion date of 2017-04-03, and a status of terminated. A reason for termination is not reported in the registry record. The allocation field does not describe a randomized assignment, and there is no masking. Consequently, the cohort descriptions are not randomized treatment-versus-control comparisons. The registry record does not report further protocol details about dose-escalation decisions or the statistical design.
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: A total of 18 patients were assigned to study treatment. 6 patients were identified with GCP violations; hence, only 12 patients were included in disposition.
Overall Study
| Stage | Serelaxin: Cohort 1 | Serelaxin: Cohort 2 | Serelaxin: Cohort 3 |
|---|---|---|---|
| STARTED | 8 | 3 | 1 |
| Low-dose | 2 | 3 | 1 |
| High-dose | 6 | 0 | 0 |
| COMPLETED | 8 | 3 | 1 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All appropriately consented enrolled subjects who were exposed to study drug regardless of the exposure and have at least one post-baseline safety assessment.
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: Safety Set
| Characteristic | Unit | Serelaxin: Cohort 1 | Serelaxin: Cohort 2 | Serelaxin: Cohort 3 | Total |
|---|---|---|---|---|---|
| Participants analysed | 8 | 3 | 1 | 12 | |
| Age, Continuous | Years | 11.1 (SD 3.23) | 2.7 (SD 1.53) | 0.7 (SD NA) | 8.1 (SD 5.17) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 7 | 3 | 1 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 | 2 | 0 | 7 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 3 | 0 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death, measured over through 28 days + 30 days SAE follow up after completion or discontinuation from the study.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Patients |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts patients who experienced treatment-emergent adverse events, serious adverse events and death. It is a patient-count endpoint: the reported quantity concerns whether patients had events, rather than the total number of event episodes. The outcome description specifically includes confirmed systolic blood pressure decreases and worsening heart failure as examples of treatment-emergent adverse events.
Safety outcomes are used to characterize undesirable events observed during exposure and follow-up. Counting affected patients can make the frequency of people experiencing events easier to interpret than a raw event total when one person might experience more than one event. These are general considerations; the registry record does not explain why this particular endpoint or its components were selected.
The stated timeframe is through 28 days plus 30 days of serious-adverse-event follow-up after completion or discontinuation from the study. The population definition requires exposure to study drug and at least one post-baseline safety assessment, regardless of the exposure. Therefore, the endpoint is not described as applying to every enrolled subject regardless of exposure or assessment. The registry record does not report a separate analysis plan for patients with incomplete follow-up, nor does it give a statistical comparison for this endpoint.
Counts of affected patients describe observed safety experience in this study. On their own, they do not establish that an event was caused by serelaxin, and this single-group study does not provide a randomized control group for estimating comparative risk.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record reports safety counts by serelaxin cohort. In Cohort 1, 3 of 8 patients were reported with a serious adverse event and 6 of 8 with another adverse-event category. In Cohort 2, the corresponding counts were 1 of 3 and 3 of 3. In Cohort 3, the record reports 0 of 1 for each category. Each cohort reports 0 deaths. These are descriptive counts from a small dose-escalation study, not estimates from a randomized comparison.
The cohort counts should be interpreted separately. The study was not randomized, and the cohort sizes differ. The record does not describe a concurrent control group; standard care was given alongside serelaxin. The observed counts therefore cannot separate the contribution of serelaxin from underlying illness, background treatment, cohort differences, or chance. A lower count in a cohort does not by itself establish lower risk, particularly when the groups are not assigned as comparable treatment and control arms.
The serious-event terms listed include atrial thrombosis, pericardial effusion, subclavian vein thrombosis and vena cava thrombosis, each reported as 33.3%; pleural effusion, reported as 25.0%; and hypotension, reported as 12.5%. These percentages are presented as term-level figures, but the registry record does not report the denominator or further details needed to interpret how the percentages were calculated. They should not be treated as a comparative event rate or as a measure of causation.
The primary outcome is a safety measure, not an efficacy endpoint. Although the registry lists secondary cardiovascular measurements, it reports 0 analyses. Numerical results and inferential estimates for those outcomes are not reported in the registry record. There are no reported confidence intervals or hypothesis-test results for the primary outcome. Without those, the precision of the observed counts cannot be quantified using registry-reported inferential statistics.
The record's status is terminated, but a reason for termination is not reported in the registry record. That status alone does not explain the event pattern or indicate why the study stopped. Nor do zero recorded deaths in each cohort establish an absence of safety concerns: the endpoint includes other adverse events, and the observation concerns the enrolled study population and stated follow-up. The useful interpretation is limited to the events counted and terms listed, with substantial uncertainty about comparative effects and generalizability.
9. Statistical Methods Explained
Interpreting a safety result begins with identifying what was counted, who was included, and the period of observation. Here, the primary outcome counts patients with treatment-emergent adverse events, serious adverse events and death. The stated population consists of enrolled subjects exposed to study drug who had at least one post-baseline safety assessment. The timeframe extends through 28 days plus 30 days of serious-adverse-event follow-up after completion or discontinuation. These definitions matter: a patient count is not the same as an event count, and a result from an exposed, assessed safety population is not necessarily a count for every enrolled person.
What does a patient count show?
A patient count indicates how many people in the stated group had an event under the registry's outcome definition. It does not tell how many episodes each affected patient experienced, how long events lasted, or how severe every event was. The record separately identifies serious adverse events and other adverse-event figures by cohort, but does not provide a full event-level account in the registry record described. The listed serious-event terms add detail about event types; they do not replace the patient-level endpoint.
In general, event counts are descriptive. A count can be useful for identifying observed safety experiences, but its interpretation depends on the group definition, follow-up, and completeness of event ascertainment. Small groups can produce unstable proportions: one additional event or a different classification can materially change how a small cohort appears. This is a general statistical point, not an additional result from this study.
Why does the design affect interpretation?
This study is recorded as single-group, open-label, and nonrandomized, with allocation listed as NA. In general, random assignment helps make comparison groups more alike, on average, in factors that could affect outcomes. Without it, differences among cohorts may reflect their characteristics, dose-escalation sequence, clinical course, or other factors, rather than an intervention effect. An open-label design also means the record does not describe masking of treatment assignment. That can matter for the observation or classification of outcomes, especially outcomes requiring judgment. The record does not state how outcome assessors handled this issue.
Because there is no randomized control group, a comparison of cohort counts is not a controlled estimate of serelaxin's effect. Standard care is described as background therapy, not as a separately assigned comparator. General methods for comparing independent groups cannot make the cohorts exchangeable after the fact or remove unmeasured differences. The counts are best read as observations within the study, not causal estimates.
What would uncertainty measures add?
In general, a confidence interval gives a range of values compatible with the data under a stated statistical model and conveys uncertainty around an estimate. It is not a guarantee that the true value lies in the interval, and it does not correct limitations in design or data collection. The registry record does not report confidence intervals for the primary safety counts. It also reports 0 analyses, so no inferential analysis results are listed. The precision of the observed cohort figures therefore cannot be assessed from registry-reported confidence intervals or tests.
For a binary outcome such as whether a patient experienced an event, methods often model the event probability. In small samples, approximations that work well for larger samples may perform poorly; exact or other small-sample methods may be considered in general. The record does not report which method, if any, was planned or used for inferential analysis. It would be inappropriate to attribute an unreported method to the investigators.
What do the planning assumptions represent?
The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such a calculation is a design illustration, not evidence that the current study had a particular probability of detecting an effect. It is not observed power, and it does not establish that a future study would reproduce the observed effect. No planning-illustration sample-size values are reported in the registry record.
More generally, sample-size planning depends on the outcome, target effect, variability or event frequency, analysis method, and design assumptions. Results from a small exploratory study may give an uncertain estimate of the effect used in later planning. The registry record does not report the trial's own sample-size justification or a statistical analysis plan, so those details cannot be inferred from the planning assumptions.
How should the serious-event percentages be read?
The record lists percentages for selected serious adverse-event terms. Percentages describe a numerator in relation to some denominator, but the denominator and calculation details for these term-level figures are not reported in the registry record. Terms may also represent overlapping experiences rather than mutually exclusive groups; the record does not clarify this. The percentages should therefore be read as listed descriptors, not combined or interpreted as comparative risks. General statistical interpretation requires the denominator, event definition, and accounting rules to be clear.
Overall, the reported cohort counts and term percentages provide descriptive safety information. They do not supply a randomized estimate, a confidence interval, or a causal conclusion. Statistical methods can quantify sampling uncertainty under assumptions, but they cannot make a nonrandomized single-group design answer a comparative question it was not structured to answer.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 17 outcome measures, including the primary safety outcome and secondary cardiovascular measurements. When a study evaluates many outcomes, the chance of at least one apparently notable result can increase if each is tested separately. In general, multiplicity methods can control or describe this issue, but their appropriateness depends on the planned questions and analysis strategy. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan.
The record reports 0 analyses. It therefore does not provide inferential results for the listed outcomes, such as hypothesis tests or confidence intervals. This absence should not be interpreted as evidence that no event occurred or that an outcome had no change. It means the registry record does not report those analysis results.
The primary population definition includes enrolled subjects exposed to study drug who had at least one post-baseline safety assessment, regardless of exposure. This definition identifies the population for the stated safety endpoint, but the record does not explain how missing assessments, incomplete follow-up, or missing outcome data were handled. The number of participants with missing data and the reasons for any missingness are not reported in the registry record.
In general, missing data can affect both the size and interpretation of an analysis. The consequences depend on why information is missing and on the analysis population and assumptions used. Without a reported missing-data approach or accounting of incomplete observations, the extent to which missingness could influence the reported counts cannot be assessed. The record also does not report whether any sensitivity analyses were conducted.
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 |
|---|---|---|---|
| Serelaxin: Cohort 1 | 3 | 8 | 37.5% |
| Serelaxin: Cohort 2 | 1 | 3 | 33.3% |
| Serelaxin: Cohort 3 | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Serelaxin: Cohort 1 | 0 of 8 |
| Serelaxin: Cohort 2 | 0 of 3 |
| Serelaxin: Cohort 3 | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Serelaxin: Cohort 1 | 6 of 8 |
| Serelaxin: Cohort 2 | 3 of 3 |
| Serelaxin: Cohort 3 | 0 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Serelaxin: Cohort 1 | Serelaxin: Cohort 2 | Serelaxin: Cohort 3 |
|---|---|---|---|---|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 2 of 8 | 0 of 3 | 0 of 1 |
| Atrial thrombosis | Cardiac disorders | 0 of 8 | 1 of 3 | 0 of 1 |
| Pericardial effusion | Cardiac disorders | 0 of 8 | 1 of 3 | 0 of 1 |
| Hypotension | Vascular disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Subclavian vein thrombosis | Vascular disorders | 0 of 8 | 1 of 3 | 0 of 1 |
| Vena cava thrombosis | Vascular disorders | 0 of 8 | 1 of 3 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Serelaxin: Cohort 1 | Serelaxin: Cohort 2 | Serelaxin: Cohort 3 |
|---|---|---|---|---|
| Headache | Nervous system disorders | 2 of 8 | 0 of 3 | 0 of 1 |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 1 of 8 | 1 of 3 | 0 of 1 |
| Hypotension | Vascular disorders | 2 of 8 | 0 of 3 | 0 of 1 |
| Supraventricular extrasystoles | Cardiac disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Tachycardia | Cardiac disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Ventricular tachycardia | Cardiac disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Abdominal pain | Gastrointestinal disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Nausea | Gastrointestinal disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Non-cardiac chest pain | General disorders | 1 of 8 | 0 of 3 | 0 of 1 |
| Pneumonia viral | Infections and infestations | 0 of 8 | 1 of 3 | 0 of 1 |
Serious events with the highest arm-level rate: atrial thrombosis (33.3%), pericardial effusion (33.3%), subclavian vein thrombosis (33.3%), vena cava thrombosis (33.3%), pleural effusion (25.0%).
The cohort-level safety figures report serious adverse events and another adverse-event category separately. Cohort 1 reports 3 of 8 patients with serious adverse events and 6 of 8 with other adverse events. Cohort 2 reports 1 of 3 and 3 of 3, respectively. Cohort 3 reports 0 of 1 in each category. Each cohort reports 0 deaths. These figures are descriptive counts, not comparisons with a randomized control group.
The serious-event terms listed are atrial thrombosis, pericardial effusion, subclavian vein thrombosis and vena cava thrombosis, each at 33.3%; pleural effusion at 25.0%; and hypotension at 12.5%. The denominator and calculation details for these percentages are not reported in the registry record. Do not treat the percentages as additive, as mutually exclusive categories, or as evidence that serelaxin caused the events.
In general, serious adverse events and all adverse events are distinct safety concepts; a serious event is not simply a synonym for a severe symptom. The registry record does not provide event-level narratives or a causal assessment for these terms. The counts describe what was recorded in the study, within its stated population and follow-up.
12. What the Result Does, and Does Not, Mean
The posted results describe adverse events observed in cohorts receiving intravenous serelaxin alongside standard therapy for acute heart failure. The primary endpoint focuses on the number of patients with treatment-emergent adverse events, serious adverse events and death. The record also lists selected serious-event terms and term-level percentages. These observations can inform a descriptive account of safety experience in this study population.
They do not show what would have happened to comparable patients receiving standard care without serelaxin. There was no randomized comparator, and the study is recorded as single-group. Cohort differences therefore cannot be attributed to dose or treatment without further evidence. In general, causal interpretation requires a design and analysis that address alternative explanations; the registry record does not report such a comparative analysis.
The safety counts also do not establish whether serelaxin improves heart failure outcomes. Although secondary measurements include changes in cardiovascular pressures and arterial oxygen saturation, numerical outcome analyses are not reported in the registry record. The stated study purpose includes pharmacokinetics and tolerability, but results for those areas are not reported in the registry record.
The absence of deaths reported in each cohort is a limited observation for this study, not proof that serious safety risks are absent. The cohort counts are small, and a zero count does not rule out events outside the observed participants or follow-up. Likewise, the term-level percentages cannot be interpreted as comparative risks because their denominators and calculation details are not reported.
The most defensible reading is that the registry contains descriptive safety counts from a terminated, open-label, dose-escalation study and does not provide inferential analyses. The reason for termination, the statistical analysis plan, the handling of missing data, and any comparative estimates are not reported in the registry record. These gaps limit how far the observations can be generalized or used to answer treatment-effect questions.
13. Why This Trial Matters Statistically
This trial is statistically notable because it studies a pediatric population hospitalized with acute heart failure using a dose-escalation approach, while the available primary outcome is a safety count rather than a randomized comparison of treatment effects. Safety information in this setting can be important to characterize, but the design determines what conclusions the data can support.
The record makes the distinction between observed events and comparative evidence especially relevant. Cohort-specific counts can describe what happened among exposed participants who had a post-baseline safety assessment. Without random allocation and a control group, those counts do not estimate how outcomes differ from what would have occurred under another treatment strategy. This is a core design principle: statistical analysis cannot remove all confounding simply by comparing the recorded cohorts.
The registry also illustrates why outcome definitions and denominators matter. The primary endpoint specifies a safety population and follow-up period, while the selected serious-event terms are accompanied by percentages whose denominators are not reported. Readers need those details to interpret frequency and precision. Small cohort sizes further mean that descriptive counts can be sensitive to individual observations; this is a general statistical consideration, not a recalculated result.
Finally, the listed secondary measures and planning assumptions do not substitute for reported analyses. The record reports 0 analyses, so no inferential conclusions can be drawn from those listings. The study's status is terminated, but a reason is not reported in the registry record. Taken together, the record is useful for understanding the intended safety focus and the limits of the posted data, while leaving comparative effectiveness and the precision of estimates unresolved.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation is the single-group, nonrandomized, open-label design. There is no separately assigned control group, so cohort counts cannot provide a like-for-like comparison or isolate a treatment effect. Standard care is background therapy, not a randomized comparator. The record does not report adjustment for differences among cohorts or a method for causal inference.
The registry reports enrollment of 12, with cohort-level figures of 8, 3 and 1 at risk for the displayed safety categories. These small groups limit the stability and precision of descriptive comparisons. No confidence intervals or inferential outcome analyses are reported; the registry lists 0 analyses. The reported counts therefore should not be read as precise estimates of event probability.
The registry does not report the denominator or calculation details for the serious-event term percentages. It also does not report event-level narratives, causal assessments, missing-data methods, reasons for incomplete follow-up, or sensitivity analyses. The primary population is defined by exposure and at least one post-baseline safety assessment, so its results may not represent every enrolled subject.
The record lists multiple secondary outcomes, but numerical results for them are not reported in the registry record. It does not report a multiplicity approach, a statistical analysis plan, or the trial's sample-size justification. The status is terminated, and the reason for termination is not reported in the registry record. These limitations restrict interpretation to the descriptive details and prevent conclusions about comparative treatment effects or the full safety profile.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure — NCT02151383.
- Registry record last updated 2019-06-25; status last verified 2019-05.
- Results first posted 2019-06-25.
- 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
NCT02151383 is a Phase 2, multicenter, open-label, single-group dose-escalation study of intravenous serelaxin added to standard care in pediatric patients hospitalized with acute heart failure. The registry reports enrollment of 12, a start date of 2014-09-05, a primary completion date of 2017-04-03, and terminated status.
The primary outcome counts patients with treatment-emergent adverse events, serious adverse events and death during the stated follow-up. Cohort-level safety counts and selected serious-event terms are reported, but the registry lists 0 analyses. The study has no randomized comparator; the reason for termination, inferential results, missing-data methods and statistical analysis plan are not reported in the registry record.