Aliskiren and Valsartan vs Valsartan Alone in Patients With Stage II Systolic Hypertension and Type II Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aliskiren and Valsartan vs Valsartan Alone in Patients With Stage II Systolic Hypertension and Type II Diabetes Mellitus (NCT00927394), a randomized phase 4 study. The primary outcome is Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (MASBP) at Week 8.

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, double-blind, parallel-group, multicenter, active-controlled study. The registry record lists an enrollment of 1143 and a completed status. The study began in 2009-05, with primary completion recorded as 2011-10. Those registry dates describe the study record; they do not establish when each participant was treated or followed.

The comparison was combination therapy with aliskiren and valsartan versus valsartan monotherapy in patients with stage 2 systolic hypertension and type 2 diabetes mellitus. Placebo preparations for both drugs were included in the intervention descriptions. The descriptions say that participants took a total of 4 tablets or capsules daily to support blinding during the 8-week treatment period. The full dosing and titration details are not reported in the registry record because the monotherapy description is truncated.

Randomization and double masking are features intended to reduce differences in treatment assignment and expectations that could influence measured outcomes. A parallel-group design assigns participants to a treatment group and compares outcomes between groups rather than having each participant receive both regimens. These general design features do not by themselves establish that all possible sources of bias were eliminated.

The primary outcome analysis was not based on everyone listed in the enrollment figure. It used the Full Analysis Set 2 with ambulatory monitoring, defined in the record as Cohort 2 patients assigned through randomization who had valid baseline and post-baseline ambulatory blood pressure assessments. The registry record does not report the original sample-size justification, detailed randomization procedures, allocation concealment procedures, or the complete analysis plan.

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: Full Analysis Set 2 (FAS 2) with ambulatory blood pressure monitoring (ABPM)- Consists of all patients in Cohort 2 to whom study treatments were assigned through randomization and who had both valid baseline and post-baseline ambulatory blood pressure monitoring (ABPM)assessments.

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 24-hour Ambulatory Systolic Blood Pressure (MASBP) at Week 8, measured over baseline, week 8.

The primary endpoint was change from baseline in mean 24-hour ambulatory systolic blood pressure at week 8, measured in mmHg. Ambulatory monitoring collects blood pressure measurements across the day and night rather than relying only on a clinic visit. In this trial, the mean hourly systolic blood pressure was calculated for post-dosing hours 1-24, and each patient’s endpoint value was the average of available hourly means across those hours.

Change from baseline expresses how the measure moved during the study relative to its starting value. Negative changes in the posted group summaries indicate decreases in mean ambulatory systolic blood pressure. The endpoint was suited to the study’s antihypertensive efficacy question because it captured systolic pressure over a full 24-hour period at the week 8 assessment. The registry record identifies baseline and week 8 as the timeframe.

Ambulatory monitoring is also the reason the primary endpoint analysis population was restricted to patients with valid baseline and post-baseline monitoring assessments. That restriction makes the reported comparison specific to the defined Full Analysis Set 2 rather than to every randomized or enrolled patient. The registry record does not report further details about how incomplete hourly readings were handled beyond averaging each patient’s available hourly means.

7. Results Posted in the Registry

• Monotherapy: Valsartan: mean -11.50 versus -15.30 on control; difference 3.80 (95% CI 1.57 to 6.03), standardized effect d = 0.26; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Monotherapy: Valsartan: mean -18.20 versus -21.70 on control; difference 3.50 (95% CI 1.34 to 5.66), standardized effect d = 0.19; z-test p = 0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Monotherapy: Valsartan than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP) at Week 8

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Monotherapy: Valsartan: mean -6.70 versus -9.20 on control; difference 2.50 (95% CI 1.16 to 3.84), standardized effect d = 0.28; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Monotherapy: Valsartan than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (MAPP) at Week 8

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Monotherapy: Valsartan: mean -4.70 versus -6.10 on control; difference 1.40 (95% CI 0.12 to 2.68), standardized effect d = 0.17; z-test p = 0.032.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Monotherapy: Valsartan than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover several related aspects of blood pressure: sitting systolic and diastolic measures, ambulatory diastolic pressure and pulse pressure, sitting pulse pressure, blood pressure control, responder status, and plasma renin activity. The numerical summaries discussed in the posted results include change in mean sitting systolic pressure and changes in ambulatory diastolic pressure and ambulatory pulse pressure. The other listed secondary outcomes are not reported in the registry record in the numerical details.

The available numerical secondary summaries follow the same broad direction as the primary result: both groups had negative average changes, and the recalculated mean contrasts favor a greater average reduction in the combination group for the reported blood pressure measures. This directional agreement provides context for the primary endpoint, but it does not convert several related outcomes into independent confirmation. The measures assess overlapping aspects of blood pressure, and their results are not independent pieces of evidence simply because they have different names.

The secondary comparisons are unadjusted recalculations from posted group summaries. The sitting systolic comparison has a mean difference of 3.5 mmHg, with a 95% confidence interval from 1.342 to 5.658 and p = 0.001. The ambulatory diastolic comparison has a mean difference of 2.5 mmHg, with a 95% confidence interval from 1.16 to 3.84 and p < 0.001. The ambulatory pulse-pressure comparison has a mean difference of 1.4 mmHg, with a 95% confidence interval from 0.12 to 2.68 and p = 0.032. These results are not adjusted for testing multiple endpoints.

Unadjusted secondary findings carry less weight because examining multiple outcomes can increase the chance that some appear noteworthy by chance. The registry record does not report a multiplicity strategy, a hierarchy of secondary outcomes, or sponsor-reported analyses for these measures. The secondary pattern can therefore be treated as supportive descriptive context, not as proof that every measured blood pressure outcome has a distinct confirmed effect. It also cannot resolve the absence of numerical results for the other listed outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)
• Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP) at Week 8
• Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (MAPP) at Week 8
• Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)
• Change From Baseline in Mean Sitting Pulse Pressure (MSPP) at Week 8
• Percentage of Patients Achieving Blood Pressure Control
• Percentage of Responders
• Change From Baseline in Plasma Renin Activity (PRA) at Week 8

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each patient has a blood pressure change measured in mmHg. A group mean summarizes the average change, while a standard deviation describes how dispersed the individual changes are around that mean. These quantities answer different questions. The mean describes the group’s central result; the standard deviation describes variability between patients. The posted primary summaries give a mean and standard deviation for each treatment group.

What does the mean difference represent?

The recalculated comparison subtracts the combination-group mean change from the valsartan-alone mean change, yielding a mean difference of 3.8 mmHg. Because both group means are negative, the positive difference indicates that the mean reduction was greater in the combination group. The sign depends on which group is subtracted from which, so the comparison’s direction must be read alongside the group means. It is an unadjusted contrast based on the posted summaries, not a covariate-adjusted treatment effect.

Random assignment supports a between-group comparison by aiming to make treatment groups comparable on average at the outset. However, a recalculation from summary statistics cannot adjust for baseline variables, missing measurements, or other features of the original analysis. The registry record does not report a model or covariate adjustment for its own primary analysis. It also lists no reported analyses for this endpoint, so the recalculated estimate should be understood as a descriptive statistical reconstruction, not as a substitute for a sponsor-reported model.

How should the standard deviation and standard error be read?

The standard deviations of 14.62 and 14.75 mmHg indicate substantial spread in individual changes around the group means. Such spread can coexist with a more precisely estimated mean when the group contains many observations. The standard error quantifies sampling uncertainty in a mean estimate under the calculation; the posted values are 0.791 for the combination group and 0.821 for valsartan alone. A standard error is not the same as the standard deviation and does not describe the spread of individual patient outcomes.

The primary outcome definition also matters for interpretation. Each patient’s mean ambulatory systolic pressure was calculated by averaging available hourly means across post-dosing hours 1-24, then change from baseline was assessed at week 8. As a general statistical point, averaging repeated measurements can represent a broader time window than a single measurement, but the precise contribution of missing hourly readings depends on how available observations are distributed. The registry record says that available hourly means were used; further missing-reading procedures are not reported in the registry record.

What do the confidence interval and p-value express?

A confidence interval gives a range of estimates compatible with the observed data under a statistical procedure and its assumptions. The primary recalculated interval, from 1.567 to 6.033 mmHg, is for the between-group mean difference, not for either group’s mean change separately. It does not mean that a specified proportion of individual patients had effects within that range. A p-value summarizes how unusual a result at least as discrepant as the observed one would be under a specified null model; it is not the probability that a treatment is ineffective.

The primary p-value is unadjusted and reported as p < 0.001. It does not account for testing multiple outcomes or comparisons. The registry record does not report a multiplicity adjustment or the sponsor’s inferential procedure for the primary comparison. As a general statistical matter, selecting among multiple outcomes or analyses can increase the chance of a chance-positive result if no adjustment or prespecified testing strategy is used. The record does not allow the full testing strategy to be reconstructed.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variation is greater than a statistical model assumes. If a model understates variability, its standard errors can be too small and its intervals too narrow. The primary endpoint is continuous and is summarized with means and standard deviations, so the posted summary statistics permit an unadjusted mean comparison. The registry record does not report a model-based variance assessment or a formal test for over-dispersion. No conclusion about such a diagnostic should be inferred from the available summaries.

In short, the posted primary summaries support a transparent unadjusted comparison of average changes, with uncertainty expressed by a confidence interval. They do not disclose the full sponsor analysis, the analysis model, or all data-handling decisions. Those distinctions are important when interpreting a registry-based reconstruction.

11. Confidence Intervals and Precision

The primary mean difference is 3.8 mmHg, with a 95% confidence interval from 1.567 to 6.033. The interval is entirely above zero under the stated contrast direction, which is consistent with a larger mean reduction in the combination group in this unadjusted calculation. It gives a range of plausible values for the between-group mean difference under the calculation’s assumptions. It is not an interval for individual responses and does not show how many patients experienced a particular degree of change.

The interval’s width reflects both the estimated contrast and its sampling uncertainty. The group standard deviations, 14.62 and 14.75 mmHg, show that individual changes varied more widely than the estimated mean difference. This is not a contradiction: group means can be estimated with greater precision than individual outcomes when data are available from many patients. Precision of a mean contrast should not be confused with uniformity of response.

The interval is a recalculated, unadjusted interval from the posted summary statistics. It is not reported as the sponsor’s own confidence interval, and the registry record does not report the sponsor’s inferential method for this outcome. The p-value, p < 0.001, is likewise an unadjusted recalculation. Neither should be read as accounting for possible multiplicity across the primary and secondary outcomes.

Precision also has a population and timeframe. The primary analysis used the monitoring-defined Full Analysis Set 2 and concerns change to week 8. It does not quantify uncertainty for people outside that analysis population or for longer-term outcomes. The confidence interval describes statistical uncertainty in the estimated average contrast; it cannot resolve limitations in analysis-population selection, missing-data handling, or clinical interpretation.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants and not event counts. They illustrate the sample sizes associated with detecting different fractions of the observed primary effect under the listed planning assumptions. The registry record does not report the trial’s original sample-size justification or original design assumptions, so these figures should not be treated as a reconstruction of the trial’s design.

The calculation assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect represent progressively smaller target effects. For the primary comparison, the figures for 80% power are 235, 417, and 938 participants per arm, respectively; the corresponding figures for 90% power are 314, 558, and 1,256 participants per arm.

In plain language, 80% power means that, under the calculation’s assumptions and if the target effect were the true effect, a study of the stated size would have an 80% chance of detecting an effect at the specified significance level. The 90% column describes the analogous chance as 90%. Power is a design-stage probability under assumptions, not a measure of the chance that a result is true. These figures are planning illustrations based on the observed effect, not observed power.

Smaller effects are harder to distinguish from random variation, so detecting them with the same target power generally requires more participants. That pattern is illustrated by the increasing per-arm figures as the target fraction moves from the observed effect to 75% and then 50%. The estimates depend on the stated assumptions; different allocation, variability, analysis methods, or target effect could change planning requirements.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.800; pooled standard deviation σ = 14.683.
2. n = 2 × (1.96 + 0.842)² × 14.683² / 3.800² = 234.4, rounded up to 235 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 3.8                      # observed difference in means
sigma <- 14.6832810085645                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(927394)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 235 (80% power), 314 (90% power)
 75% of observed effect: n per arm = 417 (80% power), 558 (90% power)
 50% of observed effect: n per arm = 938 (80% power), 1,256 (90% power)
power.t.test: 235.3 
Simulated power at n = 235 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and multiple secondary outcomes. It does not report a multiplicity adjustment, a sequence for testing outcomes, or a hierarchy that specifies which secondary hypotheses were confirmatory. The recalculated p-values discussed for the primary and reported secondary measures are unadjusted. Consequently, they should not be interpreted as if the number of outcomes examined had no bearing on the chance of observing at least one small p-value.

This is a general statistical issue: when many hypotheses are tested, the probability of one or more chance-positive results can rise unless the analysis accounts for multiplicity or uses a prespecified testing strategy. The record does not establish whether such procedures were used in the sponsor’s full analysis. The absence of a reported procedure should be described as a reporting limitation, not as proof that no procedure was used.

Missing-data handling is also not reported in the registry record beyond the primary population definition and the use of each patient’s available hourly means. The Full Analysis Set 2 with ambulatory monitoring includes randomized Cohort 2 patients with valid baseline and post-baseline ambulatory assessments. This requirement means the primary endpoint estimate applies to that defined analysis population. The record does not report how many randomized patients lacked valid assessments, why assessments were missing, or whether imputation or sensitivity analyses were used.

The registry record lists an enrollment of 1143, while the primary endpoint summaries use 342 patients in the combination group and 323 in the valsartan-alone group. The sitting systolic summaries use 562 and 553 patients, respectively. These endpoint-specific analysis counts should not be assumed to represent the same population or the same missing-data process. The record does not report a complete accounting that links enrollment, randomized groups, exclusions, and analysis populations.

Details of the sponsor’s statistical analysis plan, including the exact inferential model, handling of protocol deviations, and any interim analyses, are not reported in the registry record. Without those details, the recalculated summaries remain useful for understanding the posted group data but cannot reproduce the full prespecified analysis.

15. 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: cardiac failure congestive (0.2%), myocardial ischaemia (0.2%), non-cardiac chest pain (0.2%), sweat gland infection (0.2%), heat exhaustion (0.2%).

The registry record reports serious adverse events in 9 participants at risk in the combination group and 9 participants at risk in the valsartan-alone group. For other adverse events, the reported affected counts are 34 in the combination group and 36 in the valsartan-alone group. The at-risk group counts are 574 and 565, respectively. These are registry counts; they are not the same analysis counts as those used for the primary ambulatory blood pressure endpoint.

Read the serious-event figures as counts of affected participants, not as a comparison adjusted for exposure time or baseline risk. The registry also lists serious-event terms with reported frequencies of 0.2% each: cardiac failure congestive, myocardial ischaemia, non-cardiac chest pain, sweat gland infection, heat exhaustion, and dehydration. These small listed percentages do not establish that the events were caused by either treatment, nor do they show the full clinical context or severity for each person.

Deaths are not reported in the registry record. The record’s adverse-event summaries alone do not establish overall comparative safety, and the counts should be interpreted within the study’s recorded population and timeframe.

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

The posted primary summaries show that both groups had a mean decrease in 24-hour ambulatory systolic blood pressure from baseline to week 8. The combination group’s mean change was -15.3 mmHg and the valsartan-alone group’s mean change was -11.5 mmHg. The unadjusted recalculated contrast was 3.8 mmHg, with a 95% confidence interval from 1.567 to 6.033 and p < 0.001. This describes a difference between group averages in the defined monitoring population.

The result does not establish what happened to every participant. Group averages can conceal varied individual changes, and the reported standard deviations indicate variability around those averages. The result also does not establish whether a change of this size is clinically important; the registry record does not provide a threshold for clinical importance or patient-level outcomes that would resolve that question.

The endpoint concerns a week 8 assessment, so it does not establish persistence after that timeframe. It is specific to patients with valid baseline and post-baseline ambulatory monitoring in Cohort 2, rather than automatically applying to all enrolled patients or to populations with different characteristics. The record does not provide enough detail to assess how those without valid measurements may differ from those included.

The recalculated comparison is unadjusted and does not represent the sponsor’s reported analysis. The registry record does not report the original analysis model, missing-data procedures, or multiplicity approach. Those omissions limit how fully the result can be assessed and reproduced. The confidence interval and p-value address statistical uncertainty under the recalculation, not all uncertainties about bias, analysis choices, or generalizability.

The result also does not establish treatment effects on outcomes beyond the blood pressure measures reported. Secondary outcomes include control, responder status, and plasma renin activity, but their numerical results are not reported in the registry record in the information assessed. No treatment recommendation or conclusion about overall benefit and harm follows from this endpoint alone.

17. Why This Trial Matters Statistically

This trial illustrates how a registry result can contain useful group summaries while leaving important parts of the analysis process undocumented. The randomized, double-blind, parallel-group design gives the treatment comparison a clear structure, and the primary endpoint is defined using ambulatory monitoring over post-dosing hours 1-24. At the same time, the posted primary analysis is restricted to a monitoring-defined population, and the registry record does not provide the full analysis plan or sponsor-reported inferential results.

Statistically, the distinction between a group mean change and a between-group contrast is central. Both groups had negative mean changes, but the comparison asks how far apart those changes were. The recalculated estimate and confidence interval communicate that contrast and its sampling precision without claiming that individual responses were uniform or that the difference is clinically important.

The trial also demonstrates why multiplicity and population definitions matter. Several related blood pressure outcomes were considered, and the record does not report how testing across them was handled. In addition, the number of patients contributing to the primary ambulatory endpoint differs from the enrollment count and from the counts in the sitting systolic summaries. Clear interpretation requires attention to the population attached to each outcome rather than treating every result as though it came from the same participants.

Finally, the planning illustrations show how the size of a target effect affects the number of participants needed under specified assumptions. They are not evidence about the trial’s original design or its observed power. Keeping design calculations, observed summaries, recalculated inference, and registry-reported analyses distinct is essential for a transparent statistical reading.

18. 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 primary endpoint analysis applies to the Full Analysis Set 2 with ambulatory monitoring, defined by randomization in Cohort 2 and valid baseline and post-baseline assessments. The registry record does not report a full participant flow, the reasons for missing assessments, or sensitivity analyses for missing data. The difference between endpoint-specific analysis counts and the enrollment figure therefore cannot be fully explained from the registry record.

The primary comparison and the secondary comparisons described are unadjusted recalculations from summary statistics. The record does not report the sponsor’s model, covariate adjustment, inferential method, or multiplicity strategy. This prevents direct evaluation of how the recalculations compare with the prespecified analysis. The reported secondary outcomes also span multiple related measures, while numerical details are not reported for every listed outcome.

The primary endpoint is measured at week 8. Longer-term blood pressure outcomes are not reported in the registry record. The study population is specifically described as patients with stage 2 systolic hypertension and type 2 diabetes mellitus; the registry results alone do not establish how the findings apply to other populations.

The arm descriptions are incomplete in the registry record. The combination description identifies aliskiren 150 mg and valsartan 160 mg, while the valsartan-alone description is truncated during its dosing and titration details. The record also does not report the original sample-size justification. Safety summaries are counts over the stated at-risk groups, and deaths are not reported; the available event counts do not provide a complete basis for assessing comparative safety.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Aliskiren and Valsartan vs Valsartan Alone in Patients With Stage II Systolic Hypertension and Type II Diabetes Mellitus — NCT00927394.
• Registry record last updated 2012-12-06; status last verified 2012-12.
• Results first posted 2012-10-31.
• 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.

22. Record Summary

The registry record describes a completed phase 4, randomized, double-blind, parallel-group, multicenter, active-controlled study of aliskiren plus valsartan versus valsartan alone in patients with stage 2 systolic hypertension and type 2 diabetes mellitus. Enrollment is listed as 1143. The study began in 2009-05, and primary completion is recorded as 2011-10.

The primary outcome was change from baseline in mean 24-hour ambulatory systolic blood pressure at week 8. The reported group means were -15.3 mmHg for combination therapy and -11.5 mmHg for valsartan alone. An unadjusted recalculation gives a mean difference of 3.8 mmHg, with a 95% confidence interval from 1.567 to 6.033 and p < 0.001. The registry record does not report the sponsor’s inferential analysis for this endpoint.

The result is specific to the defined ambulatory monitoring analysis population and timeframe. The registry record does not report the original sample-size rationale, full missing-data procedures, or multiplicity strategy.