Study of the Efficacy and Safety of Aliskiren HCTZ vs Ramipril in Obese Patients (BMI ≥ 30) With Stage 2 Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Efficacy and Safety of Aliskiren HCTZ vs Ramipril in Obese Patients (BMI ≥ 30) With Stage 2 Hypertension (NCT00772577), a randomized phase 4 study. The primary outcome is Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP).

2. Clinical Question

The study asks a comparative question about change in a continuously measured blood-pressure outcome over an 8-week treatment period. Its registry record identifies the two randomized treatment groups and specifies the primary endpoint as change from baseline in mean sitting systolic blood pressure, measured in mm Hg. The trial is described as prospective, multicenter, double-blind, active-control, and parallel-group.

The question is narrower than whether either treatment changes blood pressure in general. It concerns the endpoint as defined for this particular population, treatment period, and study protocol. It also depends on how the endpoint was measured and analyzed. The record says the analysis population used a last-observation-carried-forward approach and required both treatment exposure and a valid post-baseline assessment.

The record does not report a single numerical between-group result for the primary endpoint. It therefore does not give the estimated difference in change, its confidence interval, or a p-value for the comparison. The direction, size, and precision of the comparative result cannot be established from the posted registry information. The study question is identifiable; its primary comparative answer is not reported in the registry record.

3. Trial Design

This was a Phase 4, randomized, double-blind, active-control, parallel-group study. The official title describes it as prospective and multicenter. Participants were assigned to aliskiren hydrochlorothiazide or ramipril. The registry lists total enrollment as 386. The adverse-event groups each list 193 patients at risk, but the record does not state that these counts represent the exact number randomized or analyzed for efficacy.

The study focused on obese patients with stage 2 hypertension. The title defines obesity using a body mass index of at least 30. The condition listed in the registry is hypertension. The primary efficacy period was baseline to week 8, and the record describes treatment with aliskiren HCTZ at 150/12.5 mg and 300/25 mg compared with ramipril at 5 mg and 10 mg. It does not explain the sequence, timing, or criteria for moving between those listed dose levels.

The registry gives the study start as 2008-08 and primary completion as 2009-03; its status is completed. Novartis is listed as sponsor. The available information does not state the number of participating centers, the randomization ratio, the method used to generate or conceal the allocation sequence, or whether any stratification factors were used. Those details are not reported in the registry record.

Double masking is reported, but the record does not identify which study personnel were masked or describe how masking was maintained. Parallel-group design means the registry describes distinct treatment groups rather than a crossover arrangement. The stated active-control design identifies ramipril as the comparator; it does not, by itself, establish a particular statistical framework or a conclusion about either treatment.

The enrollment total gives context for the study’s scale, but it is not a substitute for the number analyzed for the primary endpoint. The stated intent-to-treat population has additional eligibility requirements based on medication exposure and post-baseline assessment. Exact efficacy-analysis counts by group are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population (consisted of all patients who received at least one dose of study medication and had at least one valid post baseline assessment of primary efficacy variable). Last Observation Carried Forward (LOCF)

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP), measured over Baseline to week 8.

The primary endpoint is change from baseline in mean sitting systolic blood pressure (MSSBP), measured in mm Hg, from baseline to week 8. It is a continuous outcome: each patient’s measurement can take a range of values, and the registry identifies the summary parameter as a mean with standard deviation as the dispersion measure.

Change from baseline expresses how the measured value at follow-up differs from the patient’s starting value. Comparing average changes between randomized groups can describe whether the groups had different mean changes over the specified period. The endpoint focuses on systolic pressure, the systolic component of a blood-pressure reading, and uses the sitting measurement as specified in the outcome definition.

General statistical context: a continuous endpoint preserves more information about the range of measured values than a classification that records only whether a threshold was crossed. A mean provides a compact summary of the group’s average, while a standard deviation describes the spread of individual measurements around that average. Neither summary alone gives the estimated between-group contrast or how uncertain that contrast is.

The registry says the primary analysis used the intent-to-treat population, defined as patients who received at least one dose and had at least one valid post-baseline assessment of the primary efficacy variable, with last observation carried forward. The record does not provide the group means, standard deviations, change estimates, or comparative uncertainty for this endpoint. The endpoint is specified, but its numerical primary result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group comparison of aliskiren HCTZ and ramipril. Random allocation is intended to make treatment groups comparable on average at the start of a trial, including with respect to factors that were not measured. This is a general property of randomization, not evidence that the groups in this particular study were balanced on every characteristic. Baseline characteristics and allocation details are not reported in the registry record.

The parallel-group structure assigns participants to one treatment group for the comparison rather than describing a sequence in which each participant receives both treatments. The record identifies double masking, which is intended in general to reduce the influence of treatment knowledge on care, reporting, or assessment. It does not specify who was masked or how the masking was implemented. The record identifies an active control, ramipril, but does not state a noninferiority or equivalence objective.

How to read the continuous endpoint

MSSBP is summarized as a mean, with standard deviation identified as the measure of dispersion. General statistical context: the mean describes the central value of a set of measurements, and the standard deviation describes how spread out those measurements are. For a change-from-baseline endpoint, the analysis can summarize each participant’s change and compare the average changes between groups. A between-group contrast is needed to answer the comparative question; the separate within-group changes are not interchangeable with that contrast.

The endpoint timeframe is baseline to week 8. This defines the follow-up interval to which the primary question applies. It does not imply that measurements were taken only at those two times, because measurement schedules beyond the stated endpoint timeframe are not reported in the registry record. The outcome description identifies the unit as mm Hg, but the numerical results by arm and the estimated contrast are not reported in the registry record.

What the analysis population means

The primary population is described as intent-to-treat, but the registry’s definition includes patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Thus, the stated definition has both a treatment-exposure condition and an assessment-availability condition. General statistical context: an analysis population should be interpreted according to its operational definition, rather than assuming that a label alone specifies who was included.

The record does not state how many patients met this definition in either group, how many were excluded from efficacy analysis, or why any patient lacked an eligible measurement. Those details matter for understanding how closely the analyzed population corresponds to the randomized population and whether missingness could affect the comparison.

Last observation carried forward

The record says the primary analysis used last observation carried forward (LOCF). In general, LOCF fills a later missing measurement with the last available measurement from that participant. It creates a value for an analysis time point, but it does not recover the unobserved measurement. Its validity depends on assumptions about the relationship between the last observed value and the missing value. If outcomes are changing over time, carrying a prior value forward may not represent the later outcome well; the direction and size of any resulting bias depend on the actual data and missingness process.

The registry record does not report how many observations were carried forward, the reasons for missing measurements, or sensitivity analyses using other missing-data approaches. The effect of LOCF on the estimate therefore cannot be assessed from the registry information.

Uncertainty and comparisons

General statistical context: a confidence interval for a between-group contrast conveys both the estimated effect and its statistical precision. A narrower interval indicates less uncertainty under the model and assumptions used; a wider interval indicates more. A p-value is not a measure of effect size, and statistical significance alone would not describe the importance of a result. Here, neither a primary contrast nor its confidence interval or p-value is reported in the registry record, so these aspects cannot be interpreted for the efficacy outcome.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated fractions refer to planning for a fraction of the observed effect. These are planning illustrations, not observed power and not a report of the trial’s own design justification. The actual numerical illustrations and the observed effect used for them are not reported in the registry record. The trial’s sample-size justification is not reported in the registry record.

What over-dispersion would mean

General statistical context: over-dispersion occurs when the observed variability is greater than a statistical model expects. It is especially relevant when analyses use count or binary outcomes and rely on a particular variance assumption; excess variability can make standard errors too small if it is ignored. The primary endpoint is described as a continuous mean, and no model details or diagnostic results are reported. There is no basis in the registry record to say that over-dispersion was assessed or present in this trial.

The record does not report the statistical model used for the primary comparison, covariate adjustment, handling of repeated measurements, assumptions checks, or whether an interim analysis was planned or conducted. These methods cannot be inferred from the randomized design, endpoint type, or LOCF statement. The sponsor’s primary analysis is not presented as a single numerical comparison in the registry record, so no recalculated estimate is available to compare with it.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary MSSBP endpoint and secondary outcomes covering diastolic blood pressure, blood-pressure control, response, and pulse pressure. It also states that the primary outcome has several categories or time points and was not reduced to one comparison. The record does not provide a detailed testing hierarchy, a multiplicity adjustment, or a prespecified rule for selecting among multiple time points or categories. These matters are not reported in the registry record.

General statistical context: when several outcomes, time points, or subgroup comparisons are tested, the chance of obtaining at least one apparently notable result can increase if each is treated as an independent primary test. Prespecifying a hierarchy or adjusting the analysis can address some multiplicity concerns. No particular adjustment can be attributed to this study from the available registry description. The number of outcome measures is listed as 5, while the number of analyses is listed as 0.

The primary population definition requires at least one dose and at least one valid post-baseline primary assessment. The record also identifies LOCF as the missing-data approach. It does not report the extent or pattern of missingness, the number of participants with carried-forward values, reasons for missing data, or sensitivity analyses. Consequently, the impact of missing measurements and the robustness of the endpoint result cannot be assessed from the registry record.

The registry does not report an interim-analysis plan, stopping rules, or a detailed statistical analysis plan. Their presence or absence cannot be inferred. It also does not report a sample-size justification for the trial. The planning illustrations described in the registry are not a substitute for such a justification and should not be read as observed power.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancreatitis (0.5%), chest pain (0.5%), non-cardiac chest pain (0.5%), dehydration (0.5%), convulsion (0.5%).

The safety record lists 193 patients at risk in each group. Serious adverse events affected 4 patients in the aliskiren HCTZ group and 2 in the ramipril group. Other adverse events affected 14 patients in the aliskiren HCTZ group and 17 in the ramipril group. These are counts of affected patients as presented in the registry, not counts of all individual event episodes.

The registry lists pancreatitis, chest pain, non-cardiac chest pain, dehydration, convulsion, and pollakiuria among the top serious adverse-event terms, each reported as 0.5%. The information given does not specify the arm for each listed term, so the terms should not be assigned to a particular treatment group. Death entries are null; deaths are not reported in the registry record.

General statistical context: adverse-event counts describe what was recorded during the study, but interpretation depends on definitions, observation time, event severity, and how events were collected. The registry information does not provide comparative confidence intervals, hypothesis tests, event-onset details, or exposure-adjusted analyses. The counts therefore describe the posted safety data without establishing a causal difference between groups.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a randomized, double-blind comparison was conducted in obese patients with stage 2 hypertension, with aliskiren HCTZ and ramipril as the study treatments. It defines the primary outcome as change from baseline to week 8 in mean sitting systolic blood pressure and describes the analysis population and LOCF approach. These details make the intended efficacy question clear.

They do not provide the numerical answer to that question. The primary outcome is not reduced to a single comparison, and the record gives no arm-level MSSBP summaries, between-group estimate, confidence interval, or p-value. Therefore, the size, direction, and precision of the primary treatment contrast cannot be determined from the registry information. The absence of a reported comparative estimate is not evidence that the treatments had equal effects, nor is it evidence that one had a larger effect.

The secondary outcome definitions identify other potential measures of blood-pressure change or response, but the associated numerical results are not reported in the registry record. The adverse-event counts provide descriptive information for the listed groups. They do not, on their own, establish whether any difference is statistically reliable or attributable to treatment. The record also does not report deaths.

General statistical context: a result should be interpreted in relation to its estimate, uncertainty, analysis population, and assumptions. A nominal p-value, if available, would not by itself establish clinical importance, and a planning calculation would not show what was observed in the trial. Here, the missing comparative efficacy estimate prevents assessment of both the observed effect size and its precision.

The record also does not provide enough methodological detail to evaluate the allocation process, exact efficacy-analysis counts, missing-data pattern, or sensitivity of the result to analytical choices. The findings that can be stated are consequently limited to the trial’s design description, endpoint specification, stated analysis approach, and the posted safety counts. Broader claims about efficacy, equivalence, or comparative safety are not supported by the registry information alone.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a clearly defined research question and a reported answer. The registry specifies the population, treatment groups, primary continuous endpoint, follow-up timeframe, analysis population, and missing-data method. Those elements outline what the investigators intended to compare and how the primary analysis was described.

At the same time, the record does not provide a single primary comparison or its uncertainty. A design description cannot substitute for an effect estimate. Without the numerical contrast and confidence interval, readers cannot assess the size or precision of the primary result, regardless of the randomized design or total enrollment of 386.

The entry also illustrates why analysis-population labels and missing-data methods need operational detail. The stated intent-to-treat population excludes patients without a valid post-baseline assessment and requires exposure to study medication; LOCF is identified, but the amount and pattern of missing data are not. These choices can influence how an endpoint estimate is formed, yet their consequences cannot be evaluated from the record as described.

General statistical context: transparent reporting connects the planned question to the analysis actually performed and communicates both the estimate and its uncertainty. Reporting outcome definitions without the associated comparative result leaves an important gap between design and interpretation. The listed safety counts are useful descriptive information, but they do not fill that efficacy-reporting gap or provide an inferential comparison.

The practical statistical lesson is not a conclusion about either treatment. It is that a registry entry can document a trial’s scope and methods while leaving the central estimate unavailable. Readers should distinguish what is specified, what is numerically reported, and what cannot be assessed from the record.

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 most consequential limitation of the registry information is the absence of a single numerical primary-outcome comparison. The entry states that the primary outcome has several categories or time points and was not reduced to one comparison. No group-specific MSSBP means, changes, standard deviations, contrast, confidence interval, or p-value are reported. This prevents assessment of the direction, magnitude, and precision of the primary result.

The stated efficacy population is defined by receiving at least one dose and having at least one valid post-baseline primary assessment. The registry does not provide the number meeting that definition in each arm or explain exclusions. Although LOCF is identified, the amount and pattern of missing data and the reasons for missingness are not reported. No sensitivity analysis is described.

The record identifies randomization and double masking but does not describe sequence generation, allocation concealment, masking procedures, the randomization ratio, or participating-center count. It does not report baseline characteristics or the statistical model and covariate strategy used for the primary comparison. The sample-size justification, interim-analysis information, and detailed multiplicity plan are also not reported in the registry record.

Safety information is limited to affected-patient counts, selected serious-event terms, and the listed denominators. The record does not report comparative uncertainty, event timing, exposure-adjusted summaries, or deaths. These omissions limit interpretation of the safety counts but do not alter what the counts themselves state.

The study was designed around an 8-week endpoint; longer-term outcomes are not described in the primary endpoint information. The registry record therefore does not establish what occurred beyond that stated interval. These limitations concern the detail available in the registry record and should not be treated as evidence that unreported analyses or information do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of the Efficacy and Safety of Aliskiren HCTZ vs Ramipril in Obese Patients (BMI ≥ 30) With Stage 2 Hypertension — NCT00772577.
• Registry record last updated 2011-03-11; status last verified 2011-03.
• Results first posted 2011-03-02.
• 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.

18. Record Summary

The registry describes a completed Phase 4, randomized, double-blind, active-control, parallel-group study sponsored by Novartis. It enrolled 386 participants and compared aliskiren hydrochlorothiazide with ramipril in obese patients with stage 2 hypertension. The study start is listed as 2008-08 and primary completion as 2009-03.

The primary endpoint was change from baseline to week 8 in mean sitting systolic blood pressure. The stated intent-to-treat population required at least one dose and a valid post-baseline assessment; LOCF was specified. The registry does not report a single primary comparison or its uncertainty.

Serious adverse events affected 4 of 193 patients receiving aliskiren HCTZ and 2 of 193 receiving ramipril. Other adverse events affected 14 and 17 patients, respectively. Deaths are not reported in the registry record. The entry defines several secondary outcomes but does not provide their numerical results.