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 Aliskiren/Amlodipine/Hydrochlorothiazide (HCTZ) Versus Aliskiren/Amlodipine in US Minority Patients With Stage II Systolic Hypertension (NCT00942994), a randomized phase 4 study. The primary outcome is Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00942994 |
| Phase | Phase 4 |
| Condition | Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 412 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
US minority patients with Stage 2 hypertension. The registry record describes the study population at this level; further eligibility details are not reported in the registry record.
Intervention
Aliskiren, amlodipine, and hydrochlorothiazide (HCTZ), assigned through a forced-titration regimen. The listed schedule begins with aliskiren/amlodipine at week 0, then adds HCTZ and increases the combination at later visits. The available regimen description ends during the week 4 dose information.
Comparator
Aliskiren and amlodipine, also assigned through forced titration. The listed schedule begins with amlodipine at week 0 and progresses to aliskiren/amlodipine 300/10 mg at week 4.
Primary question
How did mean sitting systolic blood pressure change from baseline to week 8 in each treatment group, and how did those changes compare? The endpoint is described as a mean change in mmHg. Numerical group results and a between-group estimate are not reported in the registry record, so the size and precision of any difference cannot be assessed from that record.
3. Trial Design
This was a Phase 4, randomized, double-blind, active-controlled, parallel-group study. The official title describes an 8-week, multicenter, forced-titration study. The condition listed is hypertension, and the intended population was US minority patients with Stage 2 hypertension. Enrollment was 412. The registry record does not give additional detail about the participating centers or the demographic composition of the enrolled group.
The two groups received different combination regimens. In the triple-therapy group, the schedule began with aliskiren/amlodipine 150/5 mg at week 0. At week 1, participants were force titrated to aliskiren/amlodipine/HCTZ 150/5/12.5 mg, and at week 2 to 300/5/25 mg. The description of the week 4 regimen is truncated, so the final triple-therapy dose cannot be stated from the registry record. In the dual-therapy group, participants began with amlodipine 5 mg at week 0, then progressed to aliskiren/amlodipine 150/5 mg at week 1, 300/5 mg at week 2, and 300/10 mg at week 4.
Forced titration means the listed regimen involved scheduled dose changes rather than a description of individualized titration. The registry record does not report whether dose changes could be delayed or modified, or the rules for doing so. Although the study is described as double-blind, details of how masking was maintained are not reported in the registry record. The trial status is completed. Its primary completion is listed as 2010-03, and its start as 2009-06.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Aliskiren / Amlodipine / HCTZ | Aliskiren / Amlodipine |
|---|---|---|
| STARTED | 203 | 209 |
| COMPLETED | 187 | 190 |
| NOT COMPLETED | 16 | 19 |
Reasons for not completing this period:
| Reason | Aliskiren / Amlodipine / HCTZ | Aliskiren / Amlodipine |
|---|---|---|
| Adverse Event | 7 | 4 |
| Abnormal laboratory value(s) | 1 | 0 |
| Unsatisfactory therapeutic effect | 1 | 1 |
| Patient withdrew consent | 5 | 8 |
| Lost to Follow-up | 1 | 4 |
| Protocol deviation | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Analysis was based on the Full Analysis Set consisting of all patients to whom study medication had been assigned. Last-observation-carried-forward was used. Baseline was not carried forward. In the Aliskiren/Amlodipine/HCTZ group, 5 patients did not have a post baseline measure. Hence, change from baseline to week 8 is reported for 197 patients.
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 / Amlodipine / HCTZ | Aliskiren / Amlodipine | Total |
|---|---|---|---|---|
| Participants analysed | 202 | 209 | 411 | |
| Age Continuous | years | 55.7 (SD 9.79) | 54.7 (SD 10.19) | 55.2 (SD 10.00) |
| Sex: Female, Male: Female | Participants | 107 | 100 | 207 |
| Sex: Female, Male: Male | Participants | 95 | 109 | 204 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8, measured over Baseline and week 8.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in mean sitting systolic blood pressure (MSSBP) at week 8, measured in mmHg. It is a continuous outcome: each participant’s systolic blood pressure measurement contributes to a group-level mean, and the endpoint concerns the change in that mean from baseline. The registry lists baseline and week 8 as the timeframe and identifies the summary as a mean with standard deviation.
Systolic blood pressure is the upper blood pressure reading. Assessing change from baseline provides a way to describe how the group’s measured pressure changed over the treatment period, while comparing changes between randomized groups addresses the trial’s stated question about the two regimens. In general, a mean summarizes the center of a set of measurements, and a standard deviation describes their spread. Neither measure alone gives the uncertainty in the estimated difference between groups; that usually requires an appropriate confidence interval or other inferential result.
The registry record does not report the baseline or week 8 means, the mean changes, standard deviations, or a between-group effect estimate for this endpoint. It therefore does not establish the direction, magnitude, or precision of the observed comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the trial’s comparison and identifies its primary outcome, but it does not include numerical results for that outcome. The primary endpoint is change from baseline in mean sitting systolic blood pressure at week 8. No group means, changes, standard deviations, confidence interval, or test result for this comparison are reported in the registry record. Consequently, the observed size and direction of the difference between the regimens cannot be described from this record.
This absence matters for interpretation. A trial question and a completed study do not, by themselves, show what the observed data were. Without an estimated between-group difference, it is not possible to assess whether the groups’ changes were close together or far apart. Without an uncertainty interval, it is not possible to judge how precisely that difference was estimated. A p-value alone, even if one were reported, would not convey the size or clinical meaning of an effect; in this case, a primary-outcome p-value is also not reported in the registry record.
The primary analysis description identifies a Full Analysis Set consisting of all patients to whom study medication had been assigned and says that last-observation-carried-forward (LOCF) was used. It also states that baseline was not carried forward and that 5 patients in the triple-therapy group did not have a post-baseline measurement. These details describe aspects of the analysis population and missing-data handling, but do not reveal the numerical outcome results. The remaining description of the primary analysis is incomplete in the registry record.
Safety information is reported separately. Serious adverse events affected 0 participants in the triple-therapy group and 3 in the dual-therapy group, with 202 and 209 participants at risk, respectively. These counts are descriptive and do not supply a statistical comparison or establish a causal difference. Other adverse events were reported for 22 participants in the triple-therapy group and 18 in the dual-therapy group. Death counts are not reported in the registry record.
Overall, the registry record supports a description of the design, endpoint, analysis population, and selected safety counts. It does not support a conclusion about the primary efficacy comparison because its numerical results and inferential statistics are not reported.
9. Statistical Methods Explained
The study is described as randomized, double-blind, and parallel group. In general, random allocation is used to make treatment groups comparable in expectation with respect to measured and unmeasured characteristics. It does not guarantee that the groups will be identical in a particular trial. Blinding is intended to reduce the influence of treatment knowledge on participants’ reports, care, or outcome assessment, depending on who is masked. The registry record identifies double masking but does not report the operational details of the masking procedures.
What does a mean change represent?
The primary outcome is a continuous measure: change from baseline in mean sitting systolic blood pressure at week 8. A mean is the arithmetic average of measured values. A mean change describes the average within-participant change when calculated from paired measurements, though the registry record’s precise computational details are not fully reported. The listed summary measure is mean, with standard deviation as the measure of dispersion.
In general, the standard deviation describes how variable individual measurements are around their mean. It is not the same as the standard error, which describes the precision of an estimated mean. Nor is it the same as a confidence interval, which gives a range of values compatible with the data under the assumptions of the analysis. The actual means, standard deviations, and confidence intervals for the primary outcome are not reported in the registry record.
How should a between-group comparison be read?
The clinical question concerns the difference in change between the triple-therapy and dual-therapy groups. In general, an estimated difference describes the contrast between those groups; its sign depends on the order used to subtract one group from the other. The estimate’s units would be mmHg because the endpoint is measured in mmHg. A confidence interval would communicate uncertainty around that estimate, while a statistical test could assess compatibility with a specified null hypothesis. The registry record does not report the between-group estimate, its interval, or a test for the primary endpoint, so none of these features can be interpreted for this trial.
Statistical significance and effect magnitude are distinct concepts. A small p-value does not state how large an effect is, and a non-significant result does not prove that two treatments are equivalent. Equivalence or non-inferiority requires a prespecified margin and an analysis designed to evaluate that question. Such a margin and such an analysis are not reported in the registry record.
What does the analysis population mean?
The primary analysis description names a Full Analysis Set consisting of all patients to whom study medication had been assigned. This is the registry’s stated population for the endpoint. The description does not clarify all operational details, such as the handling of participants who never received medication or any additional eligibility rules for inclusion. Those details are not reported in the registry record.
The record says LOCF was used and baseline was not carried forward. In general, LOCF replaces a missing later measurement with a participant’s last observed post-baseline measurement. This approach creates an analysis value where the endpoint visit is missing, but it relies on assumptions about how the unobserved measurement relates to the last observed one. Those assumptions may be questionable when the outcome can change over time or when dropout is related to outcome. LOCF does not remove the possibility of bias, and the registry record does not report sensitivity analyses that would show whether conclusions depended on this method.
The record notes that 5 participants in the triple-therapy group lacked a post-baseline measure. It does not provide a corresponding missing-measure count for the dual-therapy group in the primary-outcome description, nor does it give reasons for missingness or a complete accounting of participants contributing to the endpoint analysis. The extent to which missing data affected the comparison therefore cannot be determined.
What is not specified?
The registry record does not report the statistical model or test used for the primary comparison, the covariates if any, the handling of departures from model assumptions, or the method used to construct uncertainty intervals. A statistical analysis plan is not reported in the registry record. Interim analyses and sample-size justification are also not reported in the registry record. These omissions mean the analysis cannot be independently reconstructed from the registry description.
The registry lists 6 outcome measures and 0 analyses. In general, when a study assesses multiple outcomes or makes multiple comparisons, multiplicity can increase the chance of false-positive findings if results are interpreted without adjustment or a prespecified hierarchy. Whether any multiplicity strategy was used is not reported in the registry record. Since numerical primary results are absent, the interpretation cannot be based on statistical significance or the apparent size of the observed effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies 6 outcome measures, including the primary endpoint of change from baseline in mean sitting systolic blood pressure at week 8. It also lists secondary outcomes involving change in mean sitting diastolic blood pressure, blood pressure control during 8 weeks, and responder status during 8 weeks. The record reports 0 analyses. It does not give a complete account of how each outcome was analyzed or the numerical results for the primary endpoint.
Multiplicity is the issue that arises when several hypotheses or outcomes are examined. In general, the more comparisons that are interpreted as confirmatory, the greater the risk that at least one apparently notable result occurs by chance. This risk can be addressed through prespecification, a hierarchy of tests, or a statistical adjustment, among other approaches. The registry record does not report whether a multiplicity strategy was used, which outcomes were treated as confirmatory, or whether analyses were adjusted.
The primary outcome description states that the analysis used a Full Analysis Set comprising all patients to whom study medication had been assigned. It also states that LOCF was used and baseline was not carried forward. The description notes that 5 patients in the triple-therapy group lacked a post-baseline measure. The number and reasons for missing primary endpoint measurements in the other group, and the sensitivity of results to alternative missing-data methods, are not reported in the registry record.
The record does not report an interim-analysis plan or the protocol’s sample-size justification. It also does not provide enough detail to verify the primary analysis specification. As a result, the impact of missing data, multiplicity, and analysis choices on the findings cannot be assessed from the registry record.
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 / Amlodipine / HCTZ | 0 | 202 | 0.0% |
| Aliskiren / Amlodipine | 3 | 209 | 1.4% |
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 / Amlodipine / HCTZ | 22 of 202 |
| Aliskiren / Amlodipine | 18 of 209 |
Most frequent serious adverse event terms
| Event term | Organ system | Aliskiren / Amlodipine / HCTZ | Aliskiren / Amlodipine |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 0 of 202 | 1 of 209 |
| Non-cardiac chest pain | General disorders | 0 of 202 | 1 of 209 |
| Nephrolithiasis | Renal and urinary disorders | 0 of 202 | 1 of 209 |
| Hypertension | Vascular disorders | 0 of 202 | 1 of 209 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Aliskiren / Amlodipine / HCTZ | Aliskiren / Amlodipine |
|---|---|---|---|
| Headache | Nervous system disorders | 22 of 202 | 18 of 209 |
Serious events with the highest arm-level rate: anaemia (0.5%), non-cardiac chest pain (0.5%), nephrolithiasis (0.5%), hypertension (0.5%).
The serious adverse event figures are counts of participants affected and counts at risk in each group. The triple-therapy group had 0 serious adverse events among 202 participants at risk; the dual-therapy group had 3 among 209 participants at risk. These are descriptive registry figures. The record does not report a statistical comparison, confidence interval, or assessment of whether the groups differed in serious adverse event risk.
The record also reports other adverse events for 22 participants at risk in the triple-therapy group and 18 in the dual-therapy group, with 202 and 209 at risk, respectively. The distinction between serious and other adverse events should be retained when reading these counts; the categories do not have the same definition. The record lists anaemia, non-cardiac chest pain, nephrolithiasis, and hypertension among the top serious adverse event terms, each reported as 0.5%. The listed terms are not accompanied by group-specific counts in the available record.
Deaths are not reported in the registry record. The adverse-event counts do not establish that treatment caused an event or that an event was unrelated to treatment. They also cannot, on their own, describe event timing, severity beyond the serious/non-serious classification, or the effect of incomplete follow-up.
12. What the Result Does, and Does Not, Mean
The record describes a randomized comparison of triple therapy with dual therapy in US minority patients with Stage 2 hypertension, using an 8-week forced-titration study design. It identifies change from baseline in mean sitting systolic blood pressure at week 8 as the primary endpoint and describes an analysis population and missing-data method. These details clarify what the trial set out to measure and some aspects of how the primary outcome was handled.
However, the numerical primary results are not reported in the registry record. There is no group-level change, between-group estimate, uncertainty interval, or primary-outcome test to interpret. Therefore the record does not establish which group had a larger change, how large any difference was, or how precisely it was estimated. It also does not establish equivalence, non-inferiority, or a treatment effect.
The safety counts offer limited descriptive information: serious adverse events were reported for 0 participants in the triple-therapy group and 3 in the dual-therapy group. Other adverse events were reported for 22 and 18 participants, respectively. These figures do not constitute a formal comparative safety analysis, and deaths are not reported in the registry record. They should not be used to infer causation or a definitive difference in risk.
General statistical interpretation requires separating the observed estimate from its uncertainty and from the design question. A completed randomized study can be informative when its outcome results and analysis are available, but design details alone cannot answer the efficacy question. Missing results should not be treated as evidence of no difference, and the absence of a reported p-value should not be interpreted as a negative finding.
13. Why This Trial Matters Statistically
Statistically, the study raises a clear comparison: a three-drug regimen versus a two-drug regimen, assessed through change in mean sitting systolic blood pressure over an 8-week treatment period. Randomization and double masking are important design features because they are intended to support a fair comparison and reduce some sources of bias. The forced-titration schedules also make the treatment contrast a comparison of regimens rather than simply a comparison of individual drug ingredients.
The registry entries illustrate why endpoint definitions and analysis populations matter. The primary measure is a change from baseline in a continuous outcome, while the analysis description names a Full Analysis Set and LOCF handling. The record also notes 5 participants in the triple-therapy group without a post-baseline measure. Those choices and missing observations can affect the interpretation of an estimated treatment contrast, so clear reporting of the methods and results is important.
The most important statistical limitation is that the primary numerical results are not reported in the registry record. Without an effect estimate and its uncertainty, readers cannot evaluate the observed difference or its precision. The listed secondary outcomes create an additional question about multiplicity, but the record does not describe a strategy for handling multiple outcomes. The safety counts are available as descriptive information, but they are not a substitute for the missing efficacy results or a comparative safety analysis.
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 registry record does not report the numerical results for the primary endpoint. This prevents assessment of the direction, magnitude, and precision of the comparison in change from baseline in mean sitting systolic blood pressure at week 8. The primary analysis description is truncated, so further details of the outcome calculation cannot be recovered from the record.
The triple-therapy arm description ends during the week 4 dose information, while the dual-therapy schedule is listed through week 4. As a result, the final triple-therapy dose is not reported in the registry record. The record also does not describe detailed eligibility criteria, participant characteristics, center-level information, adherence, or withdrawals by group.
For the primary endpoint, the record states that 5 participants in the triple-therapy group lacked a post-baseline measure and that LOCF was used, with baseline not carried forward. It does not report a complete missing-data account for both groups, reasons for missingness, or sensitivity analyses. The statistical model, inferential method, confidence-interval procedure, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record.
The safety information is limited to event counts and selected serious-event terms. Death counts and formal comparative safety estimates are not reported in the registry record. These reporting gaps constrain interpretation; they do not by themselves indicate what the unreported analyses would have found.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Aliskiren/Amlodipine/Hydrochlorothiazide (HCTZ) Versus Aliskiren/Amlodipine in US Minority Patients With Stage II Systolic Hypertension — NCT00942994.
- Registry record last updated 2011-06-08; status last verified 2011-05.
- Results first posted 2011-04-27.
- 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
This completed Phase 4 study was randomized, double-blind, active-controlled, and parallel group, with enrollment of 412. It compared aliskiren/amlodipine/HCTZ with aliskiren/amlodipine in US minority patients with Stage 2 hypertension over an 8-week forced-titration study. The primary endpoint was change from baseline in mean sitting systolic blood pressure at week 8.
The primary analysis description names a Full Analysis Set and LOCF, and notes 5 participants in the triple-therapy group without a post-baseline measurement. Numerical primary results and the main inferential statistics are not reported in the registry record. Serious adverse events were reported for 0 participants in the triple-therapy group and 3 in the dual-therapy group; deaths are not reported in the registry record.