Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension (NCT00437645), a randomized phase 3 study. The primary outcome is Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8.

2. Clinical Question

The study also assessed diastolic blood pressure, systolic response, tolerability and safety, including the proportion of patients developing peripheral edema. The posted primary outcome is a group-level comparison of change, not a report of whether each individual patient reached a particular blood pressure target. The registry gives the primary analysis population as randomized patients with a baseline and at least one post-baseline efficacy assessment. It also states that last observation carried forward was used for patients who discontinued before Week 8. The record does not report the threshold used to define a systolic response or the detailed assessment schedule for every secondary measure.

3. Trial Design

This completed phase 3 study was randomized and multicenter, with a parallel-group model listed in the registry. Enrollment was 1183. The record identifies Novartis Pharmaceuticals as the sponsor and gives a study start of 2007-01 and primary completion of 2007-11. Essential hypertension was the listed condition.

The official title describes a double-blind study, while the registry’s masking classification is quadruple. The record does not explain how these descriptions correspond to the people masked or the procedures used. The study compared valsartan/amlodipine 160/5 mg with amlodipine 10 mg in patients whose hypertension was not adequately controlled with amlodipine 5 mg alone. The registry’s eligibility description defines this as mean sitting systolic blood pressure from 130 to 160 mmHg, inclusive.

The combination arm description specifies 12 weeks of valsartan/amlodipine 160/5 mg. The amlodipine arm description specifies 8 weeks of amlodipine 10 mg, followed by a switch to the combination regimen. Although the registry categorizes the model as parallel, the comparator description therefore includes a treatment change after the primary Week 8 assessment. The record does not provide enough detail to reconcile those descriptions or to characterize every subsequent treatment period.

The primary outcome was change in mean sitting systolic blood pressure from baseline to Week 8. Blood pressure was measured at trough, defined in the record as 24±3 hours after dosing. The record also lists diastolic pressure, additional systolic and diastolic assessments, systolic response, and safety outcomes. The trial’s original sample-size justification, allocation ratio, detailed protocol, and full analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population: All randomized patients who had a baseline and at least one post-baseline efficacy assessment. For patients who discontinued prior to Week 8, the last post-baseline msSBP measurement collected was used for the analysis (last observation carried forward \[LOCF\]).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

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

The primary endpoint is change in mean sitting systolic blood pressure from baseline to Week 8, measured in mmHg. A negative change means that the measured group mean was lower at Week 8 than at baseline. The analysis reports least-squares means, which are model-based group estimates, rather than simply presenting each participant’s raw change. The reported dispersion is a standard error, describing the precision of each estimated mean.

Blood pressure was assessed with the patient seated, with the back supported and feet on the floor after a 5-minute rest. Three systolic and diastolic measurements were taken with an automated monitor and an appropriately sized cuff, and their mean was used. The arm with the highest sitting diastolic pressure at study entry was used for subsequent readings; if the inter-arm difference was less than 0.5 mmHg, the non-dominant arm was used. Measurements were taken at trough, 24±3 hours after dosing.

A change endpoint uses each participant’s starting value as a reference and summarizes the subsequent shift in the group. Systolic pressure is the primary measure in this trial; the registry also describes diastolic pressure, blood pressure response, tolerability, and safety as other interests. The endpoint alone does not describe every patient’s response or establish a target level for an individual.

7. Results Posted in the Registry

• Amlodipine 10 mg: mean -6.30 versus -8.01 on control; difference 1.71 (95% CI 0.04 to 3.38), standardized effect d = 0.12; z-test p = 0.044.

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 Diastolic Blood Pressure (msDBP) From Baseline to 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 10 mg: mean -4.13 versus -4.65 on control; difference 0.52 (95% CI -0.49 to 1.53), standardized effect d = 0.06; z-test p = 0.314.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Amlodipine 10 mg and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes extend the primary systolic assessment to diastolic pressure, other measurement times, and systolic response. The numerical secondary results posted include the Week 8 diastolic change. The overall direction of that reported result is consistent with the primary pattern, but the uncertainty is greater relative to the size of the contrast. It does not add a comparably clear statistical signal to the primary result.

Numerical results for the other listed secondary assessments, including the additional timepoints and systolic response, are not reported in the registry record. Thus, the available secondary information cannot establish whether the primary pattern persisted across visits or across the response measure. A list of planned or registered outcomes is not itself evidence of a result.

Secondary analyses generally carry less weight than a prespecified primary comparison because there may be multiple opportunities to find an apparently notable result. Unless the analysis plan controls the overall error rate or establishes a hierarchy for testing, each unadjusted p-value can overstate the strength of evidence when considered as part of a wider set of tests. The registry record does not report a multiplicity strategy or a sponsor p-value for the secondary result.

Secondary endpoints can help assess whether the primary finding has coherence across related measures, but they should be interpreted with the amount of posted information and uncertainty in mind. Here, the limited numerical reporting and missing multiplicity details mean that the secondary outcomes provide context rather than an independent confirmation of the primary comparison.

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

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
• Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
• Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a measured quantity, summarized as a mean change in mmHg. The registry reports a least-squares mean for each group and a standard error. A least-squares mean is a model-based estimate of a group mean; its exact interpretation depends on the model and any covariates or other terms included. Those model details, beyond the named ANCOVA analysis, are not reported in the registry record.

What does ANCOVA do?

Analysis of covariance, or ANCOVA, compares groups while incorporating one or more additional variables in a statistical model. In a baseline-to-follow-up trial outcome, a model can account for baseline measurements and other prespecified terms, if they are included. This may produce an adjusted group contrast that differs from a direct subtraction of the two posted group means. The registry names ANCOVA for the reported primary analysis but does not list its covariates, assumptions, or full specification.

The sponsor’s reported analysis gives a mean difference of -1.72, with a 95% confidence interval from -3.00 to -0.44. The group order in the analysis is valsartan/amlodipine followed by amlodipine, so the negative sign describes the contrast in that order. The registry labels the analysis non-inferiority or equivalence. A non-inferiority or equivalence interpretation depends on a prespecified margin and a defined hypothesis; that margin and the corresponding decision rule are not reported in the registry record. The reported classification alone is not enough to reconstruct that decision.

What is the unadjusted recalculation?

The simple recalculation contrasts the posted group mean changes without adjustment for model covariates. It uses the difference in the two group estimates and an approximate standard deviation derived from the posted standard errors and sample sizes. That approximation is useful for a basic comparison but is not a substitute for the sponsor’s ANCOVA. The recalculated contrast is 1.71 when written as amlodipine minus valsartan/amlodipine, with an unadjusted p-value of 0.044. The recalculation’s confidence interval does not include zero. Its exact bounds are not repeated in the narrative because the posted recalculated bounds have more than three decimal places.

A standard error describes the sampling precision of an estimated mean: smaller standard errors generally indicate more precise estimates, all else equal. It is not the standard deviation of individual patient measurements. The sponsor’s confidence interval and the recalculated interval address uncertainty about a group contrast, while the group-level standard errors address uncertainty about each estimated mean. These quantities should not be interchanged.

Why can the recalculation and ANCOVA differ?

A raw or unadjusted contrast uses the posted group summaries alone. ANCOVA can use baseline values and other modeled information, so it may yield a different estimate and uncertainty. The reported values are close, but even close estimates do not make the methods interchangeable. The registry record does not describe the covariates or missing-data handling used in the ANCOVA, other than its separate statement that the primary efficacy analysis used last observation carried forward for patients who discontinued before Week 8.

The p-value of 0.044 belongs to the unadjusted recalculation, not to the sponsor’s ANCOVA, for which no p-value is posted. A p-value assesses how compatible the data are with a specified null hypothesis under the calculation’s assumptions. It does not describe the size or clinical importance of an effect, and it is not the probability that the null hypothesis is true. Its unadjusted status also means it should not be treated as controlling the chance of a false positive across all outcomes.

What does over-dispersion mean in general?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. It is especially relevant to count or binary outcomes, where a simple model may underestimate uncertainty if outcomes are more variable than expected. The primary endpoint is continuous, and the registry does not report an over-dispersion assessment. The concept should not be taken as a finding about this trial.

For continuous outcomes, model assumptions about the distribution of errors, the relation between baseline and follow-up, and the handling of unusual values can affect estimated uncertainty. The registry record does not provide diagnostics for these assumptions. The three repeated blood-pressure measurements at a visit were averaged as described, but that procedure does not by itself establish that all model assumptions were met.

Finally, interpretation requires distinguishing the analysis population from the total enrollment. The primary analysis population is defined as randomized patients with a baseline measurement and at least one post-baseline efficacy assessment. Patients who discontinued before Week 8 had their last post-baseline systolic measurement carried forward. The number of patients included in that analysis and the number whose values were carried forward are not reported in the registry record.

11. Confidence Intervals and Precision

A confidence interval gives a range of values compatible with the data and the model at a stated confidence level. It communicates uncertainty in an estimated contrast; it is not a range containing a specified proportion of individual patient outcomes. The sponsor’s ANCOVA estimate is -1.72 mmHg, with a 95% confidence interval from -3.00 to -0.44 mmHg. Because the interval is for the adjusted contrast and uses the group ordering stated in that analysis, its sign should be interpreted in that direction.

The interval is on one side of zero, but it also spans a range of possible differences rather than identifying one exact value. Its width reflects sampling uncertainty together with the model and analysis choices. The registry does not give the sponsor’s ANCOVA p-value, its detailed model specification, or a confidence interval for the individual group means. The recalculated unadjusted analysis also has an interval, but its posted bounds contain more than three decimal places and are not reproduced.

Precision is different from importance. A narrow interval would indicate a more precise estimate under the analysis assumptions, while a broad interval would leave more uncertainty about the magnitude. Neither feature alone determines whether a difference is meaningful in practice. The record does not report a threshold for a meaningful systolic difference, so the clinical importance of the estimated contrast cannot be determined from these statistics alone.

Confidence intervals also do not account automatically for all design and reporting uncertainties. The primary population and LOCF approach are described, but the number of missing measurements, the covariates in ANCOVA, and any multiplicity adjustment are not reported in the registry record. Those omissions limit how fully the precision estimates can be assessed.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculation. For continuous outcomes, the listed values are participants per arm, not total participants. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider detecting the stated fraction of the observed effect. The trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the approximate number of participants per arm that would be needed, under those assumptions, for an 80% chance of detecting the selected effect if that effect were the true one. The 90% power column uses a higher chance of detection and therefore requires more participants per arm. These are design calculations for hypothetical studies, not a measure of what happened in this trial.

For the primary outcome, planning for 100% of the observed effect gives 1,047 participants per arm for 80% power and 1,402 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,861 per arm for 80% power and 2,492 per arm for 90% power. Planning for 50% of the observed effect gives 4,187 per arm for 80% power and 5,605 per arm for 90% power. The pattern illustrates that smaller target effects require more participants to detect under the stated assumptions.

For the reported secondary diastolic outcome, the corresponding figures are 4,175 and 5,590 per arm for 100% of the observed effect; 7,423 and 9,937 per arm for 75%; and 16,700 and 22,357 per arm for 50%, for 80% and 90% power respectively. These figures are illustrations based on that outcome’s observed contrast, not a recommendation for a future study. This is not observed power: it does not describe the probability that the completed trial’s result is true or that its observed estimate would recur.

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 = 1.710; pooled standard deviation σ = 13.963.
2. n = 2 × (1.96 + 0.842)² × 13.963² / 1.710² = 1,046.7, rounded up to 1,047 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 <- 1.71                      # observed difference in means
sigma <- 13.9633793911746                     # 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(437645)
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 = 1,047 (80% power), 1,402 (90% power)
 75% of observed effect: n per arm = 1,861 (80% power), 2,492 (90% power)
 50% of observed effect: n per arm = 4,187 (80% power), 5,605 (90% power)
power.t.test: 1047.7 
Simulated power at n = 1,047 per arm: 0.795 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as an ANCOVA mean difference of -1.72 mmHg, with a 95% confidence interval from -3.00 to -0.44. The contrast is listed with valsartan/amlodipine first and amlodipine second. The unadjusted recalculation uses the posted group changes and expresses the contrast in the reverse order, amlodipine minus valsartan/amlodipine, giving 1.71 mmHg and an unadjusted p-value of 0.044. The signs differ because the group order differs; the estimates describe similar direction and magnitude.

The two analyses are not identical. The sponsor’s ANCOVA is model-adjusted, while the recalculation is a simple unadjusted comparison of posted summaries. ANCOVA’s adjustment can affect both the estimate and its uncertainty. The registry does not provide enough detail to reproduce the sponsor’s model, and its ANCOVA p-value is not reported. The recalculated p-value should therefore not be substituted for a sponsor-reported test.

The record labels the sponsor analysis non-inferiority or equivalence, but does not report the margin or the decision rule. The estimate and interval can be described, but the specific non-inferiority or equivalence conclusion cannot be independently assessed without those details. There is no discrepancy flag in the registry record, so the sponsor result and recalculation are not identified as conflicting.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, timepoints, groups, or analyses are tested. Even when each test uses the same nominal threshold, a larger collection of tests creates more opportunities for a result to appear notable by chance. Statistical plans may address this through a prespecified hierarchy, adjusted thresholds, or other procedures. The registry lists several secondary outcomes and timepoints, but a multiplicity adjustment or testing hierarchy is not reported in the registry record. The unadjusted recalculated p-value should therefore be regarded as nominal.

The primary analysis population is described as the intent-to-treat population consisting of all randomized patients with a baseline and at least one post-baseline efficacy assessment. For participants who discontinued before Week 8, the last post-baseline systolic measurement was carried forward. This last-observation-carried-forward approach assigns an earlier observed value to the later endpoint when a Week 8 value is unavailable. It makes an assumption about the unobserved outcome and may not represent the actual Week 8 value.

The registry does not report how many participants discontinued before Week 8, how many had missing measurements, or how many values were carried forward. It also does not describe sensitivity analyses for missing data or alternative analysis populations. The overall enrollment does not establish the number analyzed for the primary endpoint.

The record names ANCOVA but does not report its complete specification, including covariates and model diagnostics. It does not report the original sample-size justification, interim analyses, detailed statistical plan, or a p-value for the sponsor’s ANCOVA. These details are needed to assess prespecification, the treatment of missingness, and the extent to which multiple testing was controlled. Their absence does not establish that a procedure was or was not used; it means that it is not reported in the registry record.

16. 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: cholecystitis (0.3%), gastrointestinal haemorrhage (0.2%), gastrointestinal necrosis (0.2%), inguinal hernia (0.2%), humerus fracture (0.2%).

The registry lists 11 patients in the valsartan/amlodipine group and 8 in the amlodipine group as affected by serious adverse events, among 592 and 591 patients at risk, respectively. For other adverse events, it lists 61 affected patients among 592 at risk in the combination group and 201 among 591 at risk in the amlodipine group. These are counts as posted and should be read with their stated group denominators.

The record lists serious-event terms including cholecystitis at 0.3%, gastrointestinal haemorrhage at 0.2%, gastrointestinal necrosis at 0.2%, inguinal hernia at 0.2%, humerus fracture at 0.2%, and muscular weakness at 0.2%. The listed percentages are event-term entries, not a complete account of each patient’s overall safety experience. The record does not provide enough detail to determine timing, duration, severity beyond the serious-event classification, or whether events were judged related to treatment.

Deaths are not reported in the registry record. Adverse-event counts alone do not establish comparative risk, particularly without definitions, exposure details, and information about the handling of the treatment switch described for the amlodipine arm. These figures describe the posted safety record and should not be treated as individualized guidance.

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

The primary outcome shows a greater average reduction in mean sitting systolic blood pressure in the valsartan/amlodipine group than in the amlodipine group at Week 8. The posted group estimates are changes from baseline, and the reported ANCOVA contrast is accompanied by a confidence interval. These statistics describe group averages and their uncertainty; they do not imply that every participant experienced the same change.

The result does not by itself establish the clinical importance of the difference. The registry does not report a threshold for a meaningful change in systolic pressure, and the primary endpoint is a blood-pressure measurement rather than a broader clinical outcome. It also does not establish the long-term persistence of the measured change, since the primary comparison is at Week 8.

The analysis is limited by details not reported in the registry record, including the ANCOVA specification, the trial’s original sample-size assumptions, the multiplicity procedure, and the amount of missing data. The defined analysis population and LOCF method are useful information, but they do not reveal how many participants’ results were affected or how sensitive the findings are to other missing-data assumptions.

The record classifies the sponsor analysis as non-inferiority or equivalence but does not give the relevant margin. That prevents a reader from independently evaluating the specific criterion behind that classification. The numerical estimate and interval remain interpretable as reported statistical quantities, but they should not be converted into an unstated formal conclusion.

Safety counts are also descriptive in the absence of additional detail about exposure and event attribution. Overall, the posted data characterize an average Week 8 blood-pressure comparison and selected safety counts. They do not answer questions about unreported outcomes, longer-term effects, individual treatment choices, or whether the observed contrast meets a clinical threshold.

18. Why This Trial Matters Statistically

This trial illustrates why the direction and definition of a contrast matter. The group changes are both negative, indicating reductions from baseline, while the calculated difference changes sign depending on whether it is written as amlodipine minus combination or combination minus amlodipine. Reading the group order alongside the estimate avoids interpreting a sign without its reference.

It also demonstrates the distinction between an adjusted sponsor analysis and an unadjusted calculation from group summaries. The two estimates are close, yet they use different statistical approaches and have different reported precision. A simple recalculation can provide an accessible check on posted results, but it cannot recreate an ANCOVA whose model details are not reported.

The record’s use of a continuous change endpoint makes the estimated group difference and its confidence interval central to interpretation. A p-value alone would not communicate the size or precision of that difference. Likewise, the sponsor’s non-inferiority or equivalence classification cannot be fully assessed without the relevant margin and decision rule.

The study also raises common reporting questions: whether the registered secondary outcomes have numerical results, how multiple testing was handled, and how missing measurements affected the analysis. Naming the primary population and LOCF method helps, but missingness counts and sensitivity analyses are not reported. These distinctions help readers separate what the statistical result supports from what remains uncertain.

19. 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 is available as a group-level change at Week 8, but the registry does not report individual-level distributions or the proportion of participants meeting a defined systolic response threshold. Numerical results for several listed secondary timepoints and the systolic response outcome are not reported in the registry record. This restricts assessment of consistency over time and across related measures.

The study descriptions require care: the official title calls the study double-blind, while the registry masking classification is quadruple. The registry identifies a parallel-group model, yet the amlodipine arm description says participants switched to the combination after Week 8. The record does not explain these descriptions in detail. This limits interpretation of later treatment periods and safety counts.

The primary analysis is described as ANCOVA, but the model terms, diagnostics, and sponsor p-value are not posted. The non-inferiority or equivalence label is not accompanied by a margin or decision rule. Multiplicity handling and the original sample-size justification are also not reported. For missing data, the record describes LOCF for early discontinuations but does not report how many participants were affected or whether sensitivity analyses were performed.

Finally, the posted safety information does not include deaths, event timing, treatment attribution, or detailed exposure information. The reported counts therefore describe recorded affected participants but cannot by themselves establish comparative safety. These limitations concern the detail available in the registry record and do not indicate that unreported procedures or analyses were necessarily absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension — NCT00437645.
• Registry record last updated 2014-11-11; status last verified 2014-11.
• Results first posted 2011-02-14.
• 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.

23. Record Summary

NCT00437645 is a completed phase 3 randomized study of valsartan/amlodipine 160/5 mg versus amlodipine 10 mg in patients with essential hypertension not adequately controlled on amlodipine 5 mg alone. Enrollment was 1183. The primary endpoint was change in mean sitting systolic blood pressure from baseline to Week 8.

The posted group estimates show reductions in both arms, with a greater average reduction in the combination group. The sponsor’s ANCOVA reports a mean difference of -1.72 mmHg and a 95% confidence interval from -3.00 to -0.44. The registry classifies the analysis as non-inferiority or equivalence but does not report the margin needed to assess that classification independently.

Interpretation is constrained by unreported analysis-plan and multiplicity details, incomplete numerical reporting for listed secondary outcomes, and limited information on missing data and safety-event attribution. The registry describes the primary analysis population and LOCF approach but not the number of participants affected by missing measurements.