Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension (NCT00413049), a randomized phase 3 study. The primary outcome is Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8).

2. Clinical Question

The clinical question is whether, among adults with mild to moderate essential hypertension that was not adequately controlled with amlodipine 5 mg monotherapy, a daily fixed combination of valsartan/amlodipine 80/5 mg is associated with a different change in mean sitting diastolic blood pressure over the study period than continuing amlodipine 5 mg alone. The primary endpoint is measured from baseline to Week 8. The registry record also posts secondary measures of sitting systolic pressure, diastolic response and control, overall control, and ambulatory blood pressure.

The posted results describe changes in blood pressure and related response or control measures during this trial. They do not establish how the results would apply to people outside the study population, different treatment regimens, or other follow-up periods. The registry record does not report the criteria used to define diastolic response, diastolic control, or overall control, so those threshold definitions cannot be assessed from the record alone.

3. Trial Design

This was a randomized, double-blind, double-dummy, parallel-group, active-controlled phase 3 study. The official title describes a multinational, multicenter study. Randomization assigns participants to treatment groups by chance; a parallel design means each participant remains in an assigned group rather than crossing between the two regimens. Double masking is intended to limit the influence of treatment knowledge on participants and study conduct, while a double-dummy approach can help maintain masking when treatment regimens differ. The registry record does not describe the specific procedures used to implement or assess masking.

The registry lists 698 participants enrolled. The primary efficacy results use 347 participants in the valsartan/amlodipine group and 349 in the amlodipine group. Those outcome counts are not a substitute for a complete participant-flow account; reasons for any differences between enrollment and analysis populations are not reported in the registry record.

The study was listed as completed. Its recorded start was 2007-01, and primary completion was 2007-11. The sponsor was Novartis. The study compared valsartan/amlodipine 80/5 mg with amlodipine 5 mg, both described as once-daily regimens in the official title. The primary endpoint was assessed through Week 8.

The registry record does not report the original sample-size justification, planned allocation ratio, detailed randomization procedures, adherence results, or a full protocol. Nor does it report how many participants completed each visit. These omissions limit assessment of the study's conduct beyond the design features and outcome information explicitly recorded.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Two patients in the valsartan/amlodipine group were excluded from the intent-to-treat population used for the efficacy analyses for having no post-baseline efficacy assessment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

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 in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8), measured over Baseline to end of study (Week 8).

The primary endpoint is change in mean sitting diastolic blood pressure, measured in mmHg, from baseline to the end of the study at Week 8. A negative change score indicates lowered blood pressure. The posted group values are least-squares means, with standard errors as the dispersion measure.

Blood pressure was measured with a calibrated aneroid or mercury sphygmomanometer. The arm with the highest sitting diastolic blood pressure at study entry was used for subsequent readings. At each visit, participants sat for five minutes before systolic and diastolic pressure were measured three times at intervals of 1-2 minutes; the mean of the three measurements was calculated. Repeated readings can reduce the influence of short-term measurement variability compared with relying on a single reading.

Diastolic pressure is the lower of the two blood pressure values, and change from baseline provides a way to describe how a continuous measurement shifted during follow-up. Comparing changes between randomized groups focuses attention on the difference in their observed trajectories, rather than on either group's change alone. The registry record does not state why this endpoint was selected over other blood pressure measures or identify a threshold for a clinically important change. Statistical evidence about a group difference should therefore be distinguished from judgments about clinical importance.

7. Results Posted in the Registry

• Amlodipine 5 mg: mean -7.10 versus -9.70 on control; difference 2.60 (95% CI 1.44 to 3.76), standardized effect d = 0.33; 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 in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (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 errors.
• Result:
  • Amlodipine 5 mg: mean -7.40 versus -11.40 on control; difference 4.00 (95% CI 2.32 to 5.68), standardized effect d = 0.35; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Amlodipine 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Patients Achieving a Diastolic Response at the End of the Study (Week 8)

• 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 5 mg: 66.8% (233/349) versus 79.3% (275/347) on control; risk difference -12.5 percentage points (95% CI -19.0 to -6.0), risk ratio 0.84 (0.77–0.92); 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 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Patients Achieving Diastolic Control at the End of the Study (Week 8)

• 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 5 mg: 64.5% (225/349) versus 75.5% (262/347) on control; risk difference -11.0 percentage points (95% CI -17.8 to -4.3), risk ratio 0.85 (0.77–0.94); 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 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover sitting systolic blood pressure, diastolic response, diastolic control, overall control, and 24-hour mean ambulatory systolic and diastolic blood pressure. Results are posted for the first three of those measures; the overall-control and ambulatory measures are listed as secondary outcomes but do not have posted results in the record. Across the available secondary findings, the direction is broadly consistent with the primary comparison: the combination group has a larger reported reduction in systolic pressure and higher reported proportions for the posted response and control measures.

This alignment can make the primary finding more coherent with related blood pressure measures, but the secondary outcomes do not simply replicate the primary endpoint. Systolic pressure is a different continuous measurement, while response and control recast measurements into categories. Categorization depends on thresholds, and those thresholds are not reported in the registry record. The 24-hour ambulatory measures address another measurement context, but no result is posted for them.

The registry lists no reported analyses for the secondary endpoints. The posted group summaries and comparison results therefore do not come with reported analysis detail equivalent to a full statistical analysis plan. The record also does not state whether secondary testing was adjusted for multiplicity. When multiple outcomes are examined, the chance of at least one apparently unusual result can increase; in general, adjustment or a prespecified hierarchy can help manage that issue. Without information on the planned testing strategy, unadjusted secondary findings carry less evidential weight than the designated primary comparison.

The secondary pattern is best treated as contextual support, not as proof that every related outcome was assessed or that all effects are equally precise. The missing posted results for some listed outcomes and absent definitions of response and control constrain interpretation. These limitations do not erase the available results, but they make the overall secondary evidence less complete than the primary result.

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

• Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8)
• Percentage of Patients Achieving a Diastolic Response at the End of the Study (Week 8)
• Percentage of Patients Achieving Diastolic Control at the End of the Study (Week 8)
• Percentage of Patients Achieving Overall Control at the End of the Study (Week 8)
• Change in 24-hour Mean Ambulatory Diastolic and Systolic BP From Baseline at the End of the Study (Week 8)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports least-squares means for the primary change endpoint and standard errors for dispersion. It also reports an unadjusted mean difference and confidence interval. The record does not provide a full statistical analysis plan, the model specification behind the least-squares means, or details of any covariates included in that model. The distinction matters: a least-squares mean is generally a model-based group estimate, but the precise adjustment and assumptions cannot be reconstructed from the registry record.

What does a change score represent?

In general, a change score is a participant's follow-up measurement relative to baseline; group summaries describe the average change in each group. A negative change indicates a lower follow-up reading than baseline in this trial's stated coding. A between-group contrast compares the group summaries, and its sign depends on the order used to form that contrast. The registry reports the mean difference as 2.6 mmHg; read alongside the group changes, this corresponds to the comparator having a less negative change than the combination group.

For a continuous outcome such as blood pressure, the mean is a measure of central tendency. The standard error describes the precision of an estimated mean, not the variability of individual observations. General statistical reasoning distinguishes the standard deviation, which describes spread among observations, from the standard error, which describes uncertainty in an estimated mean. The registry record gives standard errors for the primary group means, not standard deviations for the observed measurements.

What does the p-value address?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not quantify the size or clinical importance of a difference. The primary p-value is reported as unadjusted and <0.001. The registry does not report the precise test specification or whether the p-value was generated by the same model used for the least-squares means.

Why does the confidence interval matter?

In general, a confidence interval communicates the precision of an estimate and the range of values compatible with the data under the chosen method. A narrower interval indicates greater precision than a wider interval, all else equal. The primary interval is reported as 1.436 to 3.764 mmHg for the stated contrast. The interval does not describe the range of individual participant outcomes and does not remove uncertainty about unreported model choices or missing observations.

How should the binary outcomes be understood?

The secondary response and control outcomes are posted as percentages, with counts also present in the registry data. A risk difference compares the proportion meeting an outcome between groups. For such an estimate, the denominator and definition of the event matter. The record does not include the response or control thresholds, so readers cannot evaluate the clinical meaning of those classifications from the registry entry alone. General statistical interpretation also distinguishes an absolute difference in proportions from a relative measure such as a risk ratio; they answer different questions and should not be conflated.

Why can over-dispersion matter?

In general, over-dispersion occurs when the observed variation is greater than a model assumes. If a model understates variability, standard errors may be too small and intervals too narrow; if it overstates variability, estimates may be less precise than necessary. This concept is relevant to choosing and checking models, but the registry record does not report a dispersion assessment or enough model detail to determine whether over-dispersion was relevant to these analyses.

The primary population is identified as the intent-to-treat population, defined in the record as all randomized participants with a baseline and at least one post-baseline efficacy measurement. The registry also states that participants who did not complete the Week 8 assessment were handled using last observation carried forward. In general, this method substitutes a participant's last available observation for a later missing measurement. It relies on assumptions about what the unobserved follow-up value would have been; the record does not report sensitivity analyses or a justification for this approach.

Although the study is described as randomized and double-blind, the registry entry does not report the allocation sequence method, concealment procedures, model diagnostics, covariate adjustment, or a detailed prespecified analysis plan. These details are important for independently assessing how estimates were obtained and whether the analysis matched the intended design. Their absence does not change the values posted, but it limits the depth of statistical evaluation possible from the registry record.

11. Confidence Intervals and Precision

The primary reported contrast is 2.6 mmHg, with a 95% confidence interval from 1.436 to 3.764. This interval conveys uncertainty about the estimated group difference: it is compatible with a range of positive values under the calculation used. It is not a prediction interval for individual participants and does not indicate that individual changes are tightly clustered around the group means.

The group estimates are reported as least-squares means with standard errors of 0.42 mmHg in each arm. Standard errors are measures of precision for the estimated means; they are not standard deviations and do not summarize how much participants' measurements varied. The registry does not post confidence intervals for the arm-specific least-squares means.

Confidence intervals are useful because they pair an estimate with its uncertainty, rather than asking readers to rely only on a thresholded p-value. In general, an interval's width reflects both the amount of information and the assumptions of the method. The observed precision should be interpreted with the analysis population and the reported last-observation-carried-forward approach in mind. The amount of missing Week 8 data and the impact of alternative missing-data assumptions are not reported in the registry record.

The interval does not resolve whether the difference is clinically important. The registry record does not state a threshold for a meaningful between-group difference, so clinical importance cannot be determined from statistical precision alone. It also does not report the model specification behind the least-squares estimates, which limits independent assessment of how model assumptions contribute to the interval.

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 for 80% power and participants per arm for 90% power. These are design illustrations based on the observed effect, not a report of the original trial's enrollment calculation. The posted sample-size assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column indicates the illustrative number of participants per arm that would give an 80% chance of detecting the chosen effect under the stated assumptions, if that effect were the true one. The 90% power column represents a higher chance of detecting that effect under the same assumptions and therefore generally requires more participants per arm. These are planning calculations, not observed power.

Rows planning for 100%, 75%, and 50% of the observed effect consider progressively smaller target effects. A smaller effect is harder to distinguish from random variation, so the planning calculation requires more participants per arm to maintain the same target power. This is a general feature of study planning, not evidence that any particular future study will observe the effect used in the illustration.

The stated method says time-to-event calculations would use total events, while other outcomes use participants per arm. The outcomes in this trial are continuous or binary rather than time-to-event outcomes, so the relevant figures are participants per arm. The numbers should be read as hypothetical planning requirements under the stated assumptions, not as a recalculation of the trial's observed results or a substitute for the unreported original design rationale.

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 = 7.835.
2. n = 2 × (1.96 + 0.842)² × 7.835² / 2.600² = 142.6, rounded up to 143 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 <- 7.83503084597302                     # 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(413049)
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 = 143 (80% power), 191 (90% power)
 75% of observed effect: n per arm = 254 (80% power), 340 (90% power)
 50% of observed effect: n per arm = 571 (80% power), 764 (90% power)
power.t.test: 143.5 
Simulated power at n = 143 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 identifies one primary endpoint and lists five secondary outcomes. It does not report a multiplicity adjustment, a testing hierarchy, or a protocol-level plan specifying which secondary hypotheses were confirmatory. Since testing several outcomes can raise the chance of false-positive findings across the set, an unadjusted p-value for a secondary endpoint should not be interpreted as though it were the sole planned test. The registry's unadjusted secondary comparisons therefore have a more exploratory role unless additional prespecified analysis information is available.

Missing-data handling is partly described. The primary population is defined as randomized participants with a baseline and at least one post-baseline efficacy measurement. For participants who did not complete the Week 8 assessment, the record states that a last observation carried forward approach was used. This means the analysis does not simply use only observed Week 8 values for every participant; it carries an earlier measurement forward for some incomplete assessments.

In general, carrying the last observation forward assumes that the carried value is a reasonable stand-in for the missing later measurement. That assumption may not reflect the actual course of an outcome, and its plausibility depends on why observations are missing and how outcomes change over time. The registry record does not report the number of participants with missing Week 8 data, reasons for missingness, patterns by treatment group, or sensitivity analyses using alternative assumptions. It also does not report a complete participant-flow account.

The posted registry record lists no reported analyses for the secondary outcomes. Details of the primary model, missing-data sensitivity work, and analysis-plan deviations are not reported in the registry record. Thus the posted estimates can be described, but their robustness to alternative analysis choices cannot be fully assessed from the registry entry.

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

Serious events with the highest arm-level rate: gastric ulcer (0.3%), humerus fracture (0.3%), jaw cyst (0.3%), parathyroid tumour benign (0.3%), post herpetic neuralgia (0.3%).

The serious adverse event figures report 4 participants affected in the valsartan/amlodipine group and 2 in the amlodipine group, with 349 participants at risk in each group. The registry lists no participants affected by other adverse events in either group. These counts describe what the record reports; they do not by themselves establish a comparative safety conclusion. The registry record does not provide further detail about the definition or ascertainment period for these event categories.

The listed serious adverse event terms include gastric ulcer, humerus fracture, jaw cyst, parathyroid tumour benign, and post herpetic neuralgia, each reported as 0.3%. The record does not show how these terms were distributed between groups in the summary listing. Death counts are not reported in the registry record.

Rare-event counts can be imprecise, especially when few events are recorded. In general, a comparison of safety profiles requires attention to event definitions, follow-up duration, exposure, severity, and whether events were judged related to treatment. Those details are not reported sufficiently to draw a broad safety conclusion from these figures alone. The counts should be read as registry-reported serious events, not as a complete account of every possible adverse effect.

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

The posted primary result describes a greater average reduction in mean sitting diastolic blood pressure in the valsartan/amlodipine group than in the amlodipine group during the period ending at Week 8. The estimated between-group contrast is accompanied by a confidence interval and an unadjusted p-value, allowing readers to consider both the estimated size and its statistical precision. It is a comparison of group averages, not a statement that every participant experienced a reduction or that individual responses were uniform.

Because participants were randomized and the study was double-blind, the design includes features intended to support a fair treatment comparison and reduce bias. However, the registry entry does not provide all details needed to evaluate randomization implementation, masking success, adherence, missing data, or the statistical model. The available registry findings therefore support description of the posted comparison, while leaving uncertainties about conduct and analytic robustness.

The result does not establish clinical importance, because the registry record does not state a threshold for a meaningful change. Nor does a statistically significant result prove that the same contrast would occur in other populations, with other regimens, or over longer follow-up. The trial concerns adults with mild to moderate essential hypertension not adequately controlled with amlodipine 5 mg monotherapy, and its primary endpoint ends at Week 8.

The result also does not establish a complete benefit-harm balance. The safety summary contains limited counts, and the record does not report deaths, fuller event descriptions, or a broad set of safety analyses. Related secondary outcomes have incomplete posted results and no reported multiplicity strategy. Accordingly, the most defensible reading is a statistically distinguishable short-term group difference in the posted primary measurement, subject to the registry record's limits in clinical context, missing-data detail, and broader applicability.

17. Why This Trial Matters Statistically

This trial illustrates several statistical ideas that matter in clinical research. First, the endpoint is a continuous change score, and the registry reports both group-level estimates and a between-group contrast. Reading the contrast alongside each group's direction of change prevents confusion about which arm had the larger reduction. The confidence interval adds information about precision that a p-value alone does not convey.

Second, the distinction between standard errors and participant-level variability is important. Standard errors describe precision of the estimated means, not the range of responses among participants. The registry's reporting of standard errors, without standard deviations or a full model specification, means the group summaries can be interpreted but not fully reconstructed from the entry alone.

Third, the record makes clear that missing-data choices affect interpretation. Last observation carried forward is stated for incomplete Week 8 assessments, but the amount of missingness and sensitivity to other assumptions are not reported. A method name alone cannot show how much the primary estimate depends on that choice.

Finally, the trial has several secondary outcomes, but no reported analyses for them and no stated multiplicity strategy. This shows why results across multiple measures need a planned hierarchy or appropriate caution. The posted secondary pattern can provide context, while the primary endpoint remains the clearest focal comparison in the registry. The original sample-size rationale is also absent; illustrative calculations based on the observed effect should not be mistaken for the study's prospective design assumptions.

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 specific to this trial affect interpretation of the registry findings. The primary endpoint is assessed through Week 8, so the entry does not establish whether the reported group difference persisted beyond the recorded follow-up. The population is restricted to adults with mild to moderate essential hypertension not adequately controlled with amlodipine 5 mg monotherapy; the registry result should not be generalized automatically to other patient groups or treatment regimens.

The primary analysis population excludes randomized participants who did not have both baseline and at least one post-baseline efficacy measurement, according to the record's definition. The extent of any such exclusions is not reported. The record states that last observation carried forward was used for participants missing the Week 8 assessment, but does not report the amount of missingness, reasons for it, or sensitivity analyses. These omissions make it difficult to judge how missing outcomes may affect the estimate.

The registry does not report detailed model specifications, covariates, diagnostic checks, or a full analysis plan. It also does not report a multiplicity strategy for the secondary outcomes. Some listed secondary outcomes have no posted results, and the thresholds defining response and control are not reported. Consequently, the secondary findings cannot be assessed as a complete prespecified family of tests.

The safety summary is brief: death counts are not reported, and the registry does not give enough detail to assess event attribution, follow-up, or comparative risk with precision. The original sample-size justification and trial-specific design assumptions are also not reported. These limitations concern what can be evaluated from the registry record and do not, on their own, determine the direction or validity of the posted estimates.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension — NCT00413049.
• Registry record last updated 2011-04-29; status last verified 2011-04.
• Results first posted 2011-02-08.
• 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

NCT00413049 is a completed phase 3 randomized, double-blind, double-dummy, parallel-group study sponsored by Novartis. It enrolled 698 participants and compared once-daily valsartan/amlodipine 80/5 mg with amlodipine 5 mg in adults with mild to moderate essential hypertension not adequately controlled with amlodipine monotherapy.

The primary outcome was change in mean sitting diastolic blood pressure from baseline to Week 8. The posted primary comparison reports a mean difference of 2.6 mmHg, with a 95% confidence interval from 1.436 to 3.764 and an unadjusted p-value <0.001. The record also lists secondary blood pressure outcomes, although not all have posted results. It describes last observation carried forward for incomplete Week 8 assessments. Important details, including the original sample-size justification, full analysis plan, multiplicity handling, and extent of missing data, are not reported in the registry record.