Aliskiren HCTZ Compared to Amlodipine in Patients With Stage 2 Systolic Hypertension and Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aliskiren HCTZ Compared to Amlodipine in Patients With Stage 2 Systolic Hypertension and Diabetes Mellitus (NCT00787605), a randomized phase 4 study. The primary outcome is Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP).

2. Clinical Question

The clinical question is specifically about short-term blood-pressure change in patients who had both diabetes and stage 2 systolic hypertension. It is not a question about longer-term cardiovascular outcomes, nor does the registry record describe outcomes beyond the stated treatment period. The posted primary endpoint is continuous, measured in mmHg, and concerns the average change in sitting systolic pressure rather than the proportion of participants reaching a target. Secondary outcomes include sitting diastolic blood-pressure change, response and blood-pressure control percentages, biomarker measurements, and safety and tolerability. Their presence broadens the questions being examined, but does not make them equivalent to the primary endpoint: each captures a different aspect of treatment response or safety.

3. Trial Design

The registry record identifies this as a completed Phase 4, randomized, double-masked, parallel-group study sponsored by Novartis. Its title describes a comparison of aliskiren/HCTZ with amlodipine in patients with stage 2 systolic hypertension and diabetes mellitus. The record gives an enrollment of 860 and lists the study start as 2008-11 and primary completion as 2010-01.

The treatment schedules were not identical in dose, but each included an initial period followed by a higher dose: aliskiren/HCTZ 150/12.5 mg for 1 week followed by 300/25 mg for 7 weeks, and amlodipine 5 mg for 1 week followed by 10 mg for 7 weeks. The official title describes an 8-week study. The primary measure was assessed at baseline and Week 8. The record specifies the full analysis set, intent-to-treat, for that endpoint.

The posted primary outcome summaries include 426 participants for aliskiren/HCTZ and 429 for amlodipine. These are the arm-specific analysis counts for the reported endpoint; they should not be treated as a reconciliation of the enrollment figure. The registry record does not report the original sample-size justification, the planned allocation ratio, details of random-sequence generation, or the operational procedures used to maintain masking. A planned analysis method beyond the endpoint’s least-squares mean description is not reported in the registry record.

There are no reported secondary analyses in the record’s analysis listing, although secondary outcome results are posted. That distinction matters: an outcome result can be present without the registry record supplying a full statistical analysis plan or explaining how all planned analyses were conducted. The record also does not describe how treatment adherence, protocol deviations, or missing measurements were handled. These gaps limit how much can be inferred about the trial’s detailed conduct from the posted record alone.

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, intent-to-treat

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 and Week 8.

The primary endpoint is change from baseline in mean sitting systolic blood pressure (msSBP), measured in mmHg at baseline and Week 8. A change score describes how much the measured pressure shifted over the study period; a negative value indicates a decrease from baseline. The registry reports least-squares means for the arms, rather than only raw arithmetic averages. Least-squares means are model-based estimates, but the exact model and covariate adjustments are not reported in the registry record.

Systolic blood pressure is the upper pressure reading. Using change in a continuous measure retains information about the amount of change, rather than reducing the result to whether a participant did or did not cross a threshold. The endpoint is relevant to the study’s stated purpose of evaluating blood-pressure lowering in diabetic patients with stage 2 systolic hypertension. It also gives the comparison a common scale, in mmHg, for describing the arm-level changes and their contrast.

The primary endpoint is not a direct measure of long-term health outcomes, and it does not by itself answer whether participants achieved blood-pressure control. Those are distinct questions. The record separately lists blood-pressure control as a secondary outcome. Its results therefore should be interpreted as short-term changes in mean sitting systolic pressure, not as evidence about outcomes or follow-up that the registry does not report.

7. Results Posted in the Registry

• Amlodipine: mean -26.22 versus -28.82 on control; difference 2.60 (95% CI 0.60 to 4.60), standardized effect d = 0.17; z-test p = 0.011.

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 Diastolic Blood Pressure (msDBP)

• 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 errors.
• Result:
  • Amlodipine: mean -8.97 versus -9.92 on control; difference 0.95 (95% CI -0.19 to 2.09), standardized effect d = 0.11; z-test p = 0.104.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Amlodipine and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Responders

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Amlodipine: 68.5% (294/429) versus 74.2% (316/426) on control; risk difference -5.6 percentage points (95% CI -11.7 to 0.4), risk ratio 0.92 (0.85–1.01); unadjusted two-proportion z-test p = 0.068.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Amlodipine and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Patients Achieving Blood Pressure Control

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Amlodipine: 13.8% (59/429) versus 23.2% (99/426) on control; risk difference -9.5 percentage points (95% CI -14.7 to -4.3), risk ratio 0.59 (0.44–0.79); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Amlodipine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover related dimensions of blood-pressure response. The diastolic-pressure change is a continuous measure, while responder status and blood-pressure control are binary summaries. The posted estimates are directionally consistent in some respects with the primary systolic result, but they do not all have the same degree of precision. Their differing scales and definitions mean that the pattern should be read as complementary evidence, not as several interchangeable versions of the primary endpoint.

The registry also lists biomarker measurements and safety and tolerability among secondary outcomes. Detailed quantitative results for those topics are not reported in the registry record in the outcome results. This limits the extent to which the secondary outcome set can be interpreted as a whole. The record lists 6 outcome measures and 5 secondary outcomes, but that listing does not itself establish that every outcome has a complete numerical result or a reported analysis.

Unadjusted secondary results carry less weight for confirmatory interpretation because examining multiple outcomes creates more opportunities for apparently notable results by chance. The registry record does not report a multiplicity adjustment, a hierarchy of secondary endpoints, or which analyses were intended to support formal claims. The secondary p-values therefore describe individual comparisons without documented control of the broader testing process.

The secondary outcomes can help characterize whether the primary pattern is accompanied by related changes, but they cannot independently establish a broad treatment effect. Their interpretation depends on endpoint definitions, analysis methods, and uncertainty, some of which are not reported. The appropriate reading is descriptive: the results add context to the primary systolic comparison while remaining secondary, unadjusted findings.

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

• Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
• Percentage of Responders
• Percentage of Patients Achieving Blood Pressure Control
• Biomarker Measurements
• Evaluate the Safety and Tolerability

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary estimate represent?

The primary arm results are least-squares mean changes from baseline in mean sitting systolic blood pressure. A least-squares mean is an estimated group mean from a statistical model. It can account for features specified in that model, but the registry record does not report the model formula, covariates, or assumptions. The posted values are therefore best described by the estimator label the record gives, without assuming a particular adjustment strategy.

The comparison is reported as a mean difference for amlodipine relative to aliskiren/HCTZ. Its positive direction is consistent with the arm estimates: the amlodipine change is less negative than the aliskiren/HCTZ change. The comparison is an unadjusted recalculation based on posted summary statistics, not a recovered sponsor model. The registry record does not flag a discrepancy, but the recalculated contrast should still be distinguished from any model-based analysis that may have been used by the sponsor.

How should the standard errors be read?

The spread reported beside each primary least-squares mean is a standard error. A standard error describes the precision of an estimated mean, not the spread of individual participants’ measurements. It tends to be smaller when an estimate is more precise, but it does not describe the range of individual blood-pressure changes. The arm-level standard errors are 0.722 and 0.719. The record does not provide individual participant data or the observed standard deviation of change.

The comparison also includes a pooled standard deviation and a standardized effect estimate. The pooled standard deviation is marked as approximate, and the standardized effect estimate is 0.174. These quantities summarize the contrast on a scale adjusted for variability, but they do not replace the change measured in mmHg. Because the standard deviation is approximate, this standardized summary should be treated as a descriptive aid rather than as an independently verified analysis.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimate. It gives a range of values compatible with the observed data under the method’s assumptions. It is not a range containing every participant’s response, nor is it a probability statement about the true effect after the data have been observed. For the primary contrast, the interval from 0.603 to 4.597 lies above zero. This conveys more information than the point estimate alone: it shows the direction and precision of the contrast as calculated from the posted summaries.

The confidence interval and p-value are related ways of describing uncertainty, but neither captures every limitation of the study. In particular, they do not resolve missing-data concerns, unreported modeling choices, or the limits of applying a short-term study result to other populations or outcomes.

What does the p-value describe?

The unadjusted p-value of 0.011 describes how incompatible the observed contrast is with a null contrast under the assumptions of the test used for that calculation. It is not the probability that the null hypothesis is true, and it is not a measure of clinical importance. The exact test specification is not reported in the registry record. Because the comparison is unadjusted and the record lists multiple outcomes, the p-value should not be read as a family-wise error-controlled result.

How are secondary outcomes analyzed?

The diastolic-pressure endpoint is continuous, and its arm results are also least-squares mean changes with standard errors. The responder and blood-pressure-control endpoints are percentages. Their comparisons are expressed as risk differences, with additional relative measures listed in the posted results. A risk difference describes the absolute contrast in event proportions using the comparison’s stated arm ordering. The registry’s displayed estimates use the order of amlodipine relative to aliskiren/HCTZ; the signs should be interpreted with that ordering in mind.

Binary outcomes describe whether a defined event or status occurred, rather than the amount of change in a continuous measure. The exact operational definitions of responder and blood-pressure control are not reported in the registry record. The confidence intervals and unadjusted p-values for these endpoints communicate uncertainty in the posted comparisons, but they do not show that the outcomes were adjusted for the number of endpoints examined.

Why can over-dispersion matter?

For a binary outcome, a simple model may assume that observed variation is adequately described by the chosen probability model. Over-dispersion means that actual variation is greater than that model expects. If present and unaccounted for, standard errors may be too small and uncertainty intervals too narrow. This is a general statistical consideration; the registry record does not report an over-dispersion assessment or say whether a model requiring that assessment was used.

For continuous outcomes, the precision of a mean comparison also depends on the variability of individual measurements and on model assumptions. The posted record supplies standard errors for the arm-level estimates and an approximate pooled standard deviation for the primary contrast, but does not supply enough detail to assess all assumptions directly. The methods should therefore be understood at the level reported in the registry, rather than inferred from the labels alone.

Finally, statistical significance and effect size answer different questions. A p-value relates the observed data to a null model; the estimate and interval describe the magnitude and uncertainty of the contrast in the reported units. Interpretation should consider both, alongside study design, endpoint relevance, and limitations in the analysis details available in the registry record.

11. Confidence Intervals and Precision

The primary contrast is estimated as 2.6 mmHg for amlodipine relative to aliskiren/HCTZ, with a 95% confidence interval from 0.603 to 4.597. The interval does not include zero, so the unadjusted comparison is consistent with a positive contrast under the stated direction. In the context of the arm changes, this corresponds to a larger estimated reduction in the aliskiren/HCTZ group. The interval’s endpoints are not a guarantee that the true contrast lies within them; they describe uncertainty under the statistical method’s assumptions.

Precision is different from clinical importance. The interval indicates how precisely the contrast is estimated from the posted summaries, but the registry record does not specify a threshold for a clinically important difference. It also does not provide the full sponsor model or a model-based confidence interval that could be compared with the recalculated interval. The primary result should therefore be interpreted as a reasonably bounded estimate from the posted values, not as a complete account of all analytic uncertainty.

For secondary outcomes, interval width and location vary. The diastolic-pressure interval extends from -0.195 to 2.095, and the responder risk-difference interval extends from -0.117 to 0.004. Each includes zero. The blood-pressure-control risk-difference interval extends from -0.146 to -0.043 and is below zero. These intervals help show how much uncertainty remains around each estimate. They should not be treated as interchangeable with one another because they concern different outcome scales and definitions.

Confidence intervals do not account for all sources of uncertainty. They do not correct for examining multiple outcomes unless a multiplicity procedure is applied, and no such procedure is reported in the registry record. They also do not incorporate uncertainty caused by unreported analysis choices or missing-data handling.

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 expressed as participants per arm, not total participants or total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes a planning target: under the listed assumptions and if the specified effect were the true effect, the design would have an 80% chance of producing a statistically significant result using the stated test framework. The 90% power column represents a higher chance under those same assumptions and generally calls for more participants per arm. These are planning illustrations, not observed power.

Rows that use 100% of the observed effect use the full estimated contrast as the planning target. Rows using 75% or 50% of the observed effect plan for a smaller contrast. Smaller effects are harder to distinguish from random variation, so they require more participants per arm to reach the same power target. The figures are consequently sensitive to the effect assumed for planning, and they should not be read as evidence that the original trial used those exact assumptions.

The displays can be read as a relationship between the assumed effect size and the planned arm size: as the assumed effect gets smaller, the required sample grows. They do not forecast what a future study will observe, and they do not change the uncertainty in the current trial’s estimates. Sample-size planning and precision of a completed study are related, but they are not the same question.

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 = 2.600; pooled standard deviation σ = 14.897.
2. n = 2 × (1.96 + 0.842)² × 14.897² / 2.600² = 515.3, rounded up to 516 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 <- 2.6                      # observed difference in means
sigma <- 14.897016992601                     # 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(787605)
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 = 516 (80% power), 690 (90% power)
 75% of observed effect: n per arm = 917 (80% power), 1,227 (90% power)
 50% of observed effect: n per arm = 2,062 (80% power), 2,760 (90% power)
power.t.test: 516.3 
Simulated power at n = 516 per arm: 0.796 (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 lists several outcome measures, including a primary systolic-pressure endpoint and secondary outcomes spanning diastolic pressure, responder status, blood-pressure control, biomarkers, and safety. When several outcomes are examined, the chance of at least one apparently unusual result can increase. Statistical procedures can address that issue, for example by adjusting the threshold for interpreting results or by specifying a testing order in advance. The registry record does not report whether such a procedure was planned or used, so the posted secondary p-values should be treated as unadjusted.

The record identifies the primary population as the full analysis set, intent-to-treat. That label indicates the stated analysis population, but does not explain how participants with missing Week 8 measurements were treated. The handling of missing data, withdrawals, protocol deviations, and any imputation method is not reported in the registry record. Nor does the record report how many observations contributed to each endpoint beyond the arm-specific counts included with the results.

The detailed statistical plan is also not reported. The record does not specify the model behind the least-squares means, the covariates used, the method for deriving the reported confidence intervals, or whether any prespecified sensitivity analyses were conducted. It reports no secondary analyses in its analysis listing. Consequently, the posted outcome summaries support descriptive comparisons, but they do not reveal the complete analytic pathway from protocol to final result.

These omissions do not establish that a particular method was or was not used; they mean that the method is not reported in the registry record. Interpretation should distinguish what is posted—the arm estimates, contrasts, intervals, and unadjusted p-values—from the unreported details that would be needed to evaluate multiplicity control and robustness fully.

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: non-cardiac chest pain (0.5%), angina unstable (0.2%), rectal haemorrhage (0.2%), cholecystitis (0.2%), angina pectoris (0.2%).

The serious adverse-event figures are counts of affected participants alongside the number at risk in each arm. The record reports 3 serious adverse events among 428 at risk for aliskiren/HCTZ and 4 among 431 at risk for amlodipine. For other adverse events, it reports 28 among 428 at risk for aliskiren/HCTZ and 86 among 431 at risk for amlodipine. These are the posted counts and denominators; they should not be converted into a causal conclusion about comparative safety from the registry record alone.

The record lists serious-event terms with percentages, including Non-cardiac chest pain at 0.5%, and Angina unstable, Rectal haemorrhage, Cholecystitis, Angina pectoris, and Coronary artery disease each at 0.2%. The registry record does not make the group attribution for these listed terms clear in the information. Deaths are not reported in the registry record.

Adverse-event counts depend on the observation period, event definitions, reporting practices, and exposure. The registry record does not supply enough detail to assess those factors fully, nor does the count comparison establish the cause of any event.

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

The primary result describes a short-term difference in average sitting systolic blood-pressure change between the assigned groups. The estimated change was -28.82 mmHg with aliskiren/HCTZ and -26.22 mmHg with amlodipine, and the reported contrast was 2.6 mmHg for amlodipine relative to aliskiren/HCTZ. Both arm estimates indicate decreases from baseline; the contrast indicates a larger estimated decrease for aliskiren/HCTZ. The confidence interval gives information about uncertainty around that contrast, while the unadjusted p-value addresses compatibility with a null comparison under the test assumptions.

This result does not mean every participant had the average change, or that an individual response can be predicted from the group estimate. It does not establish the effect of either regimen beyond the measured study period. The registry record does not report longer-term follow-up or clinical outcomes such as events beyond the blood-pressure endpoints. Nor does it report a threshold for deciding whether the observed difference is clinically important.

The trial’s population was limited to patients described as having diabetes mellitus and stage 2 systolic hypertension, with the eligibility range specified in the registry summary. Generalizing the estimate to people with different conditions, blood-pressure levels, treatment histories, or follow-up circumstances requires evidence not reported in this record. The record also does not provide the detailed analysis plan, missing-data methods, or original sample-size assumptions, all of which affect how completely the estimate can be evaluated.

Secondary outcomes provide additional short-term information, but they do not turn the primary result into a comprehensive assessment of benefit and risk. Some secondary intervals include zero, and the results are unadjusted. The safety counts are also descriptive and cannot establish causation or comparative safety. The most defensible interpretation is limited to the posted outcomes, their reported precision, and the population and timeframe studied.

17. Why This Trial Matters Statistically

This trial is statistically instructive because it distinguishes an estimated group difference from the changes observed within each group. Both groups had negative mean changes, yet the primary contrast addresses how those changes differ between groups. Reading the contrast alongside its direction avoids confusing improvement within each arm with the between-arm comparison that answers the randomized question.

The result also illustrates why estimates, confidence intervals, and p-values serve different roles. The estimate gives the contrast in mmHg, the interval conveys uncertainty around it, and the unadjusted p-value describes compatibility with a null comparison under a test’s assumptions. None of these alone establishes clinical importance, and the record does not state a threshold for that judgment.

Another important distinction is between the primary endpoint and secondary outcomes. Related measures can show a mixed pattern, and multiple unadjusted comparisons should not be treated as independent confirmations. The record’s lack of a reported multiplicity plan and detailed statistical analysis makes this distinction especially relevant.

Finally, the trial demonstrates how registry reporting bounds statistical interpretation. The randomized, double-masked, parallel design and stated intent-to-treat population provide useful context, while unreported model specifications, missing-data handling, and design assumptions limit a full reconstruction of the analysis. A careful reading can describe the posted findings precisely without claiming more than the registry record supports.

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.

Several limitations are specific to the information reported for this trial. The primary outcome is measured at Week 8, so the posted result concerns short-term change only. The registry record does not report longer-term follow-up or outcomes beyond the listed blood-pressure and safety measures. The patient group is narrowly described as having diabetes mellitus and stage 2 systolic hypertension, which limits how readily the result can be extended to other populations.

The primary arm estimates are least-squares means, but the model, covariates, and estimation details are not reported in the registry record. The comparison is a simple unadjusted recalculation from posted summary statistics, and the pooled standard deviation is marked approximate. This makes the comparison useful for interpreting the posted summaries, but not a replacement for a fully specified sponsor analysis.

Missing-data procedures, withdrawals, adherence, and protocol deviations are not described. The record states the primary population as full analysis set, intent-to-treat, but does not explain how missing measurements were handled or provide sensitivity analyses. The original sample-size justification and the trial’s own planning assumptions are also not reported.

Multiple outcomes are listed, but no multiplicity strategy or testing hierarchy is reported. Secondary comparisons therefore remain unadjusted and should be interpreted cautiously. The safety information is limited to event counts, risk denominators, and selected serious-event terms; deaths are not reported, and detailed event context is unavailable. These limitations concern what can be concluded from the registry record and do not establish that unreported procedures were absent from the trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Aliskiren HCTZ Compared to Amlodipine in Patients With Stage 2 Systolic Hypertension and Diabetes Mellitus — NCT00787605.
• Registry record last updated 2016-10-27; status last verified 2011-05.
• Results first posted 2011-05-23.
• 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

NCT00787605 is a completed Phase 4 randomized, double-masked, parallel-group study sponsored by Novartis. It compared aliskiren/HCTZ with amlodipine in patients with stage 2 systolic hypertension and diabetes mellitus over an 8-week treatment period. The primary endpoint was change from baseline in mean sitting systolic blood pressure at Week 8 in the full analysis set, intent-to-treat.

The posted least-squares mean changes were -28.82 mmHg for aliskiren/HCTZ and -26.22 mmHg for amlodipine. The unadjusted mean difference was 2.6 mmHg for amlodipine relative to aliskiren/HCTZ, with a 95% confidence interval from 0.603 to 4.597 and an unadjusted p-value of 0.011. The record also posts secondary blood-pressure outcomes and adverse-event counts.

The registry record does not report the detailed statistical plan, missing-data handling, multiplicity procedures, or original sample-size justification. Findings should be interpreted in light of the short follow-up and the limits of the reported analysis details.