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 Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients With Acute Decompensated Heart Failure (NCT00894387), a randomized phase 3 study. The primary outcome is Time to Event Analysis: Number of Patients Experienced the First Confirmed Occurrence of Either Cardiovascular Death or Heart Failure (HF) Re-hospitalization Within 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00894387 |
| Phase | Phase 3 |
| Condition | Acute Decompensated Heart Failure, Congestive Heart Failure |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 1639 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients hospitalized with acute decompensated heart failure and congestive heart failure were eligible for the trial. The primary analysis population was the full analysis set, defined as randomized patients who had received at least one dose of study drug. The registry record does not give further eligibility criteria or a detailed description of the population’s clinical characteristics.
Intervention
Patients assigned to aliskiren received 150 mg once daily for 2 weeks. From week 2 up to 6 months, patients who could tolerate the study medication were up-titrated to aliskiren 300 mg once daily. This was added to standard therapy; the registry record does not describe the components of standard therapy.
Comparator
The comparison group received matching placebo on top of standard therapy. At week 2, patients who could tolerate study medication were up-titrated to matching placebo, described in the record as matching placebo of 300 mg aliskiren. The study was randomized, double-blind, parallel-group and placebo-controlled.
Primary question
The primary question was whether early aliskiren therapy, compared with placebo on top of standard therapy, was associated with a difference in time to the first confirmed cardiovascular death or heart failure re-hospitalization within 6 months of randomization. The registry record does not report the arm-level primary outcome counts or a treatment-effect estimate.
The question combines two clinically important types of event into one endpoint: cardiovascular death and hospitalization again for heart failure. The endpoint is time-to-event, so its intended focus is when a participant first experiences either event, rather than the total number of repeated events. The record describes the primary efficacy variable as time to the first confirmed occurrence and specifies an event window ending on or before Day 190, described as 189 days from randomization.
The trial enrolled 1639 participants and is recorded as completed. Those design and status details establish that the trial was conducted, but they do not answer the primary question on their own. Without the endpoint results and their statistical analysis, the registry record cannot establish the size or precision of any difference between assigned groups.
3. Trial Design
This was a phase 3, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Novartis Pharmaceuticals. The record describes quadruple masking. In general, masking is intended to limit the influence of treatment knowledge on participants’ experiences, clinical care, outcome assessment or study conduct. The record does not explain which roles were included in its quadruple-masking description.
The comparison was aliskiren added to standard therapy versus matching placebo added to standard therapy. The aliskiren regimen began at 150 mg once daily for 2 weeks; patients able to tolerate study medication were then up-titrated to 300 mg once daily from week 2 up to 6 months. The placebo arm followed a matching-placebo regimen. The record does not report adherence, dose changes beyond the described up-titration, or the details of background standard therapy.
The trial concerned patients hospitalized for acute decompensated heart failure. Its brief description frames the intervention as early initiation after hospitalization and the primary assessment as a composite of cardiovascular death or heart failure re-hospitalization within 6 months. The primary outcome description says the qualifying event had to occur on or before Day 190, identified as 189 days from randomization.
Enrollment was 1639. The record lists a start date of 2009-05, a primary completion date of 2012-08, and a status of completed. It does not report the date of final study completion, the recruitment period by site, the number of sites, or the allocation ratio. Although the study is described as randomized and parallel-group, the method used to generate or conceal the allocation sequence is not reported in the registry record.
The full analysis set consisted of randomized patients who had received at least one dose of study drug. The record does not give arm-specific analysis-set counts for the primary endpoint or explain whether additional analysis populations were used. These distinctions matter because the participants contributing to an outcome analysis can differ from the total enrollment, depending on the endpoint and analysis rules.
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: Of the 2134 screened patients (including 1 patient who was screened twice), 1639 patients were randomized.
Overall Study
| Stage | Aliskiren | Placebo |
|---|---|---|
| STARTED | 821 | 818 |
| Safety Set | 808 | 810 |
| Full Analysis Set | 808 | 807 |
| Completed Primary Efficacy Phase (6 m) | 717 | 707 |
| Completed Secondary Efficacy Phase (12m) | 654 | 640 |
| COMPLETED | 646 | 643 |
| NOT COMPLETED | 175 | 175 |
Reasons for not completing this period:
| Reason | Aliskiren | Placebo |
|---|---|---|
| Adverse Event | 44 | 45 |
| Abnormal Laboratory values | 2 | 2 |
| Unsatisfactory therapeutic effect | 0 | 1 |
| Lost to Follow-up | 3 | 5 |
| Administrative problems | 2 | 2 |
| Death | 77 | 76 |
| Protocol Deviation | 4 | 0 |
| Patient's request | 25 | 30 |
| Other (Missing) | 5 | 3 |
| Mis-randomized | 13 | 9 |
| GCP non-compliance | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) consisted of randomized patients who had received at least one dose of study drug.
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 | Aliskiren | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 808 | 807 | 1615 | |
| Age Continuous | years | 64.7 (SD 12.44) | 64.5 (SD 11.88) | 64.6 (SD 12.16) |
| Sex: Female, Male: Female | Participants | 171 | 197 | 368 |
| Sex: Female, Male: Male | Participants | 637 | 610 | 1247 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Event Analysis: Number of Patients Experienced the First Confirmed Occurrence of Either Cardiovascular Death or Heart Failure (HF) Re-hospitalization Within 6 Months, measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was time to the first confirmed occurrence of either cardiovascular death or heart failure re-hospitalization within 6 months of randomization. It is a composite time-to-event endpoint: each component can qualify as the first event, and the analysis concerns the time until that first qualifying occurrence. The registry description specifies that an event counted for the primary analysis if it occurred on or before Day 190, described as 189 days from randomization.
Combining events can capture more than one way a participant may experience an important outcome, and can increase the number of participants with an endpoint event compared with using only one component. That is a general property of composite endpoints, not a reported finding about this trial. Interpretation depends on the component definitions and on how often each component occurs. A composite result can be driven more by one component than another, so component-level results are useful for understanding what contributes to the combined endpoint.
Time-to-event endpoints use both whether an event occurred and when it occurred. In general, they can retain timing information and accommodate participants whose observed follow-up ends before an event, provided the analysis handles such follow-up appropriately. The registry record does not describe the statistical model, censoring rules, or handling of competing events for this endpoint.
The registry record does not report the primary outcome counts by group, an estimated treatment effect, a confidence interval, or a significance test. Thus, the endpoint definition is available, but the posted record does not show the primary efficacy comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial’s design and primary outcome definition, but it does not report the primary endpoint results by treatment group. It gives no arm-level count of participants experiencing the first confirmed cardiovascular death or heart failure re-hospitalization within 6 months, and no treatment-effect estimate, confidence interval or p-value for that endpoint. Consequently, the direction, size and precision of the primary comparison cannot be assessed from the registry record.
This absence of an outcome comparison is not evidence that the groups had the same result, nor is it evidence of a difference. It means the record does not provide the information needed to distinguish among those possibilities. A completed trial status and an enrollment of 1639 are not substitutes for endpoint results, and neither establishes whether an observed difference would be compatible with chance or sufficiently precise to support a useful estimate.
The primary endpoint is a composite of cardiovascular death and heart failure re-hospitalization. In general, a composite can summarize outcomes through a single analysis, but interpretation requires attention to its components. If one component occurs more often, it may contribute more to the combined result; if component effects differ, the overall composite can obscure that pattern. The registry record does not report component-specific primary results, so the contribution of each event type cannot be evaluated.
The record does provide adverse-event summaries. It lists 421 participants affected by serious adverse events among 808 at risk in the Aliskiren group, and 435 affected among 810 at risk in the Placebo group. It also lists 367 participants affected by other adverse events among 808 at risk in the Aliskiren group, and 333 affected among 810 at risk in the Placebo group. These are descriptive safety figures. They do not, by themselves, establish a causal difference between groups or provide a formal comparison adjusted for follow-up or other factors. The registry record does not give arm-specific death counts in the adverse-event summary.
Some serious adverse-event terms and percentages are listed, including Cardiac failure at 19.1%, Cardiac failure chronic at 7.7%, Cardiac failure acute at 7.4%, Cardiac failure congestive at 3.8%, Pneumonia at 3.3%, and Death at 3.1%. The record does not give the denominator or explain how these percentages were calculated in that list. They should therefore be read as registry-reported summaries, not as directly comparable group-specific risks.
Overall, the available record permits a description of the study question, design, and selected safety counts. It does not permit an efficacy conclusion about aliskiren versus placebo for the primary composite endpoint. The missing primary comparison and analysis details limit assessment of both the result and its precision.
9. Statistical Methods Explained
The registry record identifies the primary outcome as a time-to-event analysis, but does not report the model or inferential procedures used. The explanations below describe general statistical concepts; they are not claims about the analysis performed in this trial.
What does a time-to-event analysis estimate?
In general, a time-to-event analysis considers the time from a defined starting point until the first qualifying event. Here, the stated starting point is randomization, and the qualifying event is the first confirmed cardiovascular death or heart failure re-hospitalization within the specified window. This differs from simply comparing the total number of events because it retains information about event timing. It also differs from counting recurrent episodes, since the registry’s primary definition focuses on the first occurrence.
Time-to-event methods can use information from participants who have not experienced the event by the end of their observed follow-up. Such observations are often described as censored: the exact time at which an event might later occur is unknown, but the participant contributed event-free follow-up up to the observed endpoint. This approach depends on appropriate rules for censoring and follow-up. The registry record does not report those rules, how losses to follow-up were handled, or which model was used.
Why does the endpoint window matter?
The record defines the primary window as 6 months and states that an event counted if it occurred on or before Day 190, described as 189 days from randomization. Prespecifying a time window gives a common horizon for defining which events qualify. In general, changing the horizon can change the number of observed events and the interpretation of a time-to-event estimate. The registry record does not report how participants with incomplete observation before the end of this window were handled.
What does a composite endpoint require readers to consider?
A composite endpoint combines multiple event types into one outcome. In general, this can make the endpoint capture a broader range of clinically relevant experiences, while also making it important to understand the components separately. Components can differ in frequency, severity, and timing. A combined estimate does not necessarily describe the effect on each component equally. The registry identifies cardiovascular death and heart failure re-hospitalization as the primary components, but does not report separate component counts or estimates.
What would a confidence interval contribute?
In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the statistical method. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval’s location relative to a null value can help readers understand which effect sizes are compatible with the data and model. No confidence interval for the primary comparison is reported in the registry record, so the precision of the treatment effect cannot be assessed.
What is the role of a significance test?
In general, a significance test assesses how compatible the observed data are with a specified null hypothesis under the chosen model. A p-value does not measure the probability that a treatment works, nor does it describe the size or clinical importance of an effect. A p-value also does not replace an effect estimate and confidence interval. The registry record does not report a primary-outcome p-value or the testing procedure, so no significance-based interpretation is available.
How should the analysis population be understood?
The record defines the full analysis set as randomized patients who had received at least one dose of study drug. In general, analysis-population definitions determine which participants contribute to a particular estimate and can affect how closely the analysis reflects the randomized comparison. The stated definition differs from a description of every enrolled participant; the record does not report how many participants met this definition in each group or whether the primary analysis used another population. It also does not report how participants who did not receive a dose were handled.
What can planning illustrations tell readers?
In general, sample-size planning asks how much information a future study might need to detect a specified effect under stated assumptions. The planning assumptions described for this trial use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the planning quantity is the total number of events using the Schoenfeld approach; other planning quantities are participants per arm. These are planning illustrations, not observed power and not results of the trial’s efficacy analysis. The registry record does not report the trial’s original sample-size justification or establish that these assumptions were used to design the trial.
Because the primary endpoint has multiple components and a defined time window, it is not reduced to a single comparison in the analysis summary. The absence of a reported primary estimate means that no recalculated comparison or planning illustration can substitute for the sponsor’s own analysis. The registry record does not report the statistical analysis plan, model specification, adjustment variables, interim analyses, or multiplicity procedure.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when investigators test more than one outcome, time point, subgroup or treatment contrast. In general, repeated testing can increase the chance of at least one apparently unusual result under a null hypothesis. Statistical plans may address this through a hierarchy of tests, adjusted significance thresholds or other procedures. The registry lists one primary outcome and several secondary outcomes, including outcomes assessed at 1 month, 6 months and 12 months. The method used to control or interpret multiplicity is not reported in the registry record.
The record does not report a missing-data strategy for the primary endpoint or the secondary outcomes. It does not describe how incomplete follow-up, unavailable outcome information, withdrawal or missing measurements were handled. For a time-to-event analysis, general methods can use censored follow-up, but valid interpretation depends on the censoring assumptions and implementation; those details are not reported in the registry record.
The full analysis set is defined as randomized patients who received at least one dose of study drug. The record does not provide group-specific counts for that population, explain the treatment of participants who received no dose, or say whether an intention-to-treat population or another analysis set was used for the primary efficacy analysis. It also does not report whether participants were analyzed according to randomized assignment in every analysis.
These omissions do not establish that the trial lacked a multiplicity or missing-data plan. They mean those procedures cannot be assessed from the registry record. The record lists no analysis entries and does not report a statistical analysis plan or interim-analysis details.
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 |
|---|---|---|---|
| Aliskiren | 421 | 808 | 52.1% |
| Placebo | 435 | 810 | 53.7% |
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 |
|---|---|
| Aliskiren | 367 of 808 |
| Placebo | 333 of 810 |
Most frequent serious adverse event terms
| Event term | Organ system | Aliskiren | Placebo |
|---|---|---|---|
| Cardiac failure | Cardiac disorders | 147 of 808 | 155 of 810 |
| Cardiac failure acute | Cardiac disorders | 58 of 808 | 60 of 810 |
| Cardiac failure chronic | Cardiac disorders | 50 of 808 | 62 of 810 |
| Cardiac failure congestive | Cardiac disorders | 21 of 808 | 31 of 810 |
| Pneumonia | Infections and infestations | 25 of 808 | 27 of 810 |
| Death | General disorders | 21 of 808 | 25 of 810 |
| Hypotension | Vascular disorders | 24 of 808 | 16 of 810 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 20 of 808 | 18 of 810 |
| Renal failure acute | Renal and urinary disorders | 20 of 808 | 12 of 810 |
| Atrial fibrillation | Cardiac disorders | 14 of 808 | 16 of 810 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Aliskiren | Placebo |
|---|---|---|---|
| Hyperkalaemia | Metabolism and nutrition disorders | 155 of 808 | 128 of 810 |
| Hypotension | Vascular disorders | 117 of 808 | 83 of 810 |
| Cough | Respiratory, thoracic and mediastinal disorders | 59 of 808 | 53 of 810 |
| Hypokalaemia | Metabolism and nutrition disorders | 42 of 808 | 53 of 810 |
| Diarrhoea | Gastrointestinal disorders | 49 of 808 | 36 of 810 |
| Renal impairment | Renal and urinary disorders | 47 of 808 | 33 of 810 |
| Dizziness | Nervous system disorders | 35 of 808 | 43 of 810 |
Serious events with the highest arm-level rate: cardiac failure (19.1%), cardiac failure chronic (7.7%), cardiac failure acute (7.4%), cardiac failure congestive (3.8%), pneumonia (3.3%).
The registry lists serious adverse events affecting 421 participants among 808 at risk in the Aliskiren group and 435 participants among 810 at risk in the Placebo group. It lists other adverse events affecting 367 participants among 808 at risk in the Aliskiren group and 333 participants among 810 at risk in the Placebo group. These are counts of participants affected, as described in the record, rather than a formal comparison of event rates.
In general, adverse-event counts need context about definitions, observation time, completeness of collection, and how repeated events are handled. The registry record does not give those details for these summaries, nor does it report a statistical comparison of the groups. The arm-specific death counts in the adverse-event summary are not reported in the registry record.
The listed serious adverse-event terms include Cardiac failure (19.1%), Cardiac failure chronic (7.7%), Cardiac failure acute (7.4%), Cardiac failure congestive (3.8%), Pneumonia (3.3%), and Death (3.1%). The record does not specify the denominator for these percentages or explain whether they refer to participants, events, or another basis. They should not be treated as group-specific risks or directly compared with one another without that information.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized, placebo-controlled trial of aliskiren added to standard therapy in patients hospitalized for acute decompensated heart failure. Its primary question concerns time to the first confirmed cardiovascular death or heart failure re-hospitalization within 6 months. The record also describes the dosing regimen, the full analysis set definition, and selected adverse-event summaries.
What the record does not report is the central primary-outcome comparison: arm-level event counts, an estimated effect, a confidence interval or a p-value. Therefore, it does not show whether the primary composite differed between groups, how large any difference was, or how precisely an effect was estimated. The absence of a reported comparison should not be interpreted as evidence for no effect or as evidence for an effect.
Even if a primary composite estimate were available, general interpretation would depend on its components. Cardiovascular death and heart failure re-hospitalization are distinct outcomes, and a combined result would not by itself explain the result for either one. Component-level estimates, follow-up information and the analysis method would help readers understand the endpoint and the certainty of the comparison. Those primary outcome details are not reported in the registry record.
The serious and other adverse-event counts describe participants recorded as affected in each group. They do not establish that one assignment caused more or fewer events, particularly without details of ascertainment, follow-up, denominators for the listed percentages, or a formal safety comparison. The record also does not provide arm-specific death counts in its adverse-event summary.
Accordingly, the registry supports a description of the trial’s design and selected safety information, but not a conclusion about the efficacy of aliskiren for the primary outcome. The trial’s completed status and enrollment do not resolve the missing statistical result. Interpretation of efficacy requires the actual outcome estimates and their uncertainty, which are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises statistical questions common to clinical studies of acute conditions and longer-term outcomes. Patients were hospitalized for acute decompensated heart failure, while the primary endpoint followed participants for 6 months after randomization. The analysis therefore concerns events occurring over time rather than a single measurement taken at one visit. In general, time-to-event methods can use event timing and partial follow-up, but their interpretation depends on clear endpoint definitions, censoring rules and a suitable analysis method.
The composite endpoint combines cardiovascular death with heart failure re-hospitalization. This can provide a single outcome that captures more than one type of event, but the combined estimate can be difficult to interpret without component-specific results. In general, components may differ in frequency and clinical meaning, so separate estimates help reveal whether a composite result reflects a consistent pattern. The registry record does not report those component-level primary results.
The randomized, double-blind, parallel-group, placebo-controlled design is relevant to how a treatment comparison is structured. Random allocation is intended, in general, to support comparable groups at baseline, while masking can reduce some sources of bias. Those design features do not remove the need to report the outcome estimates, uncertainty, analysis population and handling of missing data. The registry record does not provide these primary analysis details.
The record’s safety summaries also illustrate why counts need context. Serious and other adverse events are reported for participants in each group, but the available summaries do not show a formal comparison or explain all relevant denominators and follow-up details. Descriptive counts can inform a reader about what was recorded, but they are not a substitute for a prespecified safety analysis.
The statistical significance of the trial cannot be judged from design information alone. A clear estimate and confidence interval would be needed to assess the magnitude and precision of the primary comparison. Since the registry record does not report them, the most important statistical contribution of this record is its specification of the question and endpoint, alongside the limits of the posted result information.
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 for interpreting efficacy is that the registry record does not report the primary outcome comparison. It gives no group-specific primary event counts, effect estimate, confidence interval or p-value. As a result, neither the direction nor the precision of the primary result can be assessed.
The record does not report the primary statistical model, censoring rules, treatment of competing events, handling of incomplete follow-up, or whether any covariates were used. These details are relevant to understanding a time-to-event analysis. The primary endpoint’s components are not reported separately, so the contribution of cardiovascular death and heart failure re-hospitalization to the composite cannot be examined.
The full analysis set is defined, but its group-specific size and the population actually used for the primary analysis are not reported. The record also does not state how participants with no dose, missing outcome data, or incomplete follow-up were handled. A multiplicity strategy for the primary and secondary outcomes is not reported, nor are interim analyses or a statistical analysis plan.
The serious adverse-event summary lists affected participants and participants at risk in each group, but does not provide a formal comparison or all details needed to interpret the listed percentages. Arm-specific death counts are not reported in that summary. The registry record also does not report the components of standard therapy, adherence, or detailed eligibility and baseline characteristics.
Finally, the registry record does not give the trial’s original sample-size justification. Planning illustrations based on an observed effect are distinct from the original design rationale and do not provide an efficacy result. These limitations restrict independent assessment of both the primary outcome and the completeness of the posted safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients With Acute Decompensated Heart Failure — NCT00894387.
- Registry record last updated 2013-11-07; status last verified 2013-10.
- Results first posted 2013-10-10.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT00894387 is a completed phase 3 randomized, quadruple-masked, parallel-group, placebo-controlled trial sponsored by Novartis Pharmaceuticals. It enrolled 1639 patients hospitalized for acute decompensated heart failure. The study compared aliskiren added to standard therapy with matching placebo added to standard therapy.
The primary endpoint was time to the first confirmed cardiovascular death or heart failure re-hospitalization within 6 months of randomization, with events counted on or before Day 190, described as 189 days from randomization. The full analysis set consisted of randomized patients who had received at least one dose of study drug.
The registry record does not report the primary outcome counts, treatment-effect estimate, confidence interval or p-value. It lists serious and other adverse-event counts by group and selected serious adverse-event terms, but does not provide a formal safety comparison. Important analysis details, including multiplicity and missing-data procedures, are not reported in the registry record.