Olmesartan/HCTZ 40/12.5 mg Combination Therapy Versus Olmesartan Medoxomil 40 mg Monotherapy in Essential Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Olmesartan/HCTZ 40/12.5 mg Combination Therapy Versus Olmesartan Medoxomil 40 mg Monotherapy in Essential Hypertension (NCT00441350), a randomized phase 3 study. The primary outcome is dBP Change After 8 Weeks Phase A.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase III, randomized, double-masked, parallel-group study of OM/HCTZ 40/12.5 and OM 40 in patients with hypertension. Enrollment is recorded as 1004, and the study status is completed. The recorded start is 2007-07 and primary completion is 2008-05. The sponsor is Menarini Group.

The brief summary describes two sequential phases, each lasting eight weeks. In Phase A, OM 40 was compared with OM/HCTZ 40/12.5 to evaluate the added benefit of the combination in essential moderate to severe hypertension. The primary endpoint is the Phase A change in mean trough sitting dBP from Week 0 to Week 8. The posted Phase A endpoint groups include 282 participants for OM 40 and 556 for OM/HCTZ 40/12.5. The record does not explain why these endpoint counts differ from the overall enrollment figure.

In the planned Phase B, patients with insufficient blood-pressure control on OM 40 were to start OM/HCTZ 40/12.5, while those with insufficient control on OM/HCTZ 40/12.5 were to be up-titrated to OM/HCTZ 40/25. The registry also reports Phase B dBP and systolic blood-pressure (sBP) outcomes by response groups. The relationship between the Phase B outcomes and the planned dose changes is not fully described in the results record; Phase B results for the 40/25 mg combination are not reported in the registry record.

Further details on sequence generation, concealment, adherence, withdrawals, analysis populations, and the original sample-size justification are not reported in the registry record. The description of randomization and masking does not by itself supply those implementation details.

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: Participants who completed the arms OM 40 mg and OM/HCTZ 40/12.5 mg, respectively in Phase A are the same ones who started, depending on being a responder or non-responder in the arms of Phase B continuing with OM 40 mg and OM/HCTZ 40/12.5 mg or uptitration to OM/HCTZ 40/12.5 mg and OM/HCTZ 40/25, respectively of Phase B.

Phase A: Randomization to Week 8

Phase B: Week 8 to Week 16

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 dBP Change After 8 Weeks Phase A, measured over Eight weeks.

The primary endpoint is the reduction in mean trough sitting dBP from baseline, defined as Week 0, to Week 8 of Phase A. It is reported as a mean change in mmHG, with a standard deviation for each group. A negative change indicates that the measured group mean was lower at Week 8 than at baseline. The endpoint therefore summarizes the average change over the treatment period; it does not show how individual participants changed or how many reached a particular blood-pressure target.

General: A continuous endpoint preserves information about the magnitude of change, rather than reducing results to a yes-or-no outcome. Sitting dBP is one component of a blood-pressure measurement, and the registered outcome specifically uses the trough sitting measurement. “Trough” refers to a measurement made at the low point of the dosing interval, but the registry does not give further measurement-timing details.

Blood-pressure change is used in this study to quantify the short-term difference between the randomized treatment groups. The registry defines the endpoint and its eight-week timeframe, but does not report the clinical threshold, if any, that would represent an important difference for patients. Nor does the mean alone establish whether all, most, or only some participants experienced a reduction. The endpoint should therefore be read as a group-level measure of change over the stated period.

7. Results Posted in the Registry

• OM/HCTZ 40/12.5: mean -18.90 versus -15.80 on control; difference -3.10 (95% CI -4.47 to -1.73), 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.

dBP Change After 8 Weeks Phase B

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OM 40 mg Non-responders: mean -9.30 versus -0.50 on control; difference -8.80 (95% CI -10.58 to -7.02), standardized effect d = -1.18; z-test p = <0.001.
  • OM/HCTZ 40/12.5 mg Responders: mean -0.30 versus -0.50 on control; difference 0.20 (95% CI -1.20 to 1.60), standardized effect d = 0.03; z-test p = 0.779.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for OM 40 mg Non-responders than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OM/HCTZ 40/12.5 mg Responders and the control. The interval gives the range of effects that remain compatible with the data.

sBP Change After 8 Weeks Phase B

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OM 40 mg Non-responders: mean -12.40 versus -0.50 on control; difference -11.90 (95% CI -14.18 to -9.62), standardized effect d = -1.23; z-test p = <0.001.
  • OM/HCTZ 40/12.5 mg Responders: mean -0.40 versus -0.50 on control; difference 0.10 (95% CI -1.46 to 1.66), standardized effect d = 0.01; z-test p = 0.900.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for OM 40 mg Non-responders than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OM/HCTZ 40/12.5 mg Responders and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists two Phase B secondary outcomes: change in dBP and change in sBP after eight weeks. Results are organized by responder and non-responder groups for OM 40 and OM/HCTZ 40/12.5. The reported ANCOVA analyses indicate differences across the Phase B groups for both outcomes. The registry also posts recalculated pairwise comparisons, which are unadjusted and should be read as supplementary contrasts rather than replacements for the sponsor’s model.

Across the secondary outcomes, the broad pattern is that the Phase B results distinguish response categories, while the primary result addresses the initial Phase A randomized comparison. These are related in topic because they measure blood-pressure change, but they answer different questions and concern different stages of the study. The Phase B summaries cannot be taken as a direct confirmation of the Phase A effect or as a single randomized comparison of the original groups.

Secondary outcomes carry less inferential weight than the prespecified primary question, particularly when multiple outcomes or comparisons are examined. General: Testing many hypotheses can increase the chance that at least one result appears statistically notable by chance. A multiplicity adjustment or a clear hierarchy of tests can address that concern, but the registry record does not report how multiplicity was handled. The secondary results should therefore be interpreted cautiously, especially where pairwise comparisons are unadjusted.

The registry does not report a complete Phase B analysis plan, adjusted effect estimates, confidence intervals for the sponsor’s ANCOVA analyses, or details sufficient to reconstruct the population comparisons. The results can describe the posted outcomes and reported analyses, but they do not establish the clinical importance of the observed changes or resolve all uncertainties about the later-phase comparisons.

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

• dBP Change After 8 Weeks Phase B
• sBP Change After 8 Weeks Phase B

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measurement, and the reported group summaries are means and standard deviations. Two kinds of evidence are relevant: the descriptive difference calculated from those summaries and the sponsor’s reported ANCOVA analysis. They are related, but they are not interchangeable.

What does the unadjusted mean difference represent?

The recalculated mean difference compares the two posted Phase A group means. Its direction depends on the stated order of subtraction: the combination group’s mean change minus the OM 40 group’s mean change. A negative value means the combination group had a more negative average change. The recalculation uses only group-level means, standard deviations, and participant counts; it does not adjust for baseline values or other covariates.

General: An unadjusted comparison is transparent and easy to relate to the observed group summaries. It can be useful as a descriptive estimate, but it may not match a model-based analysis that accounts for additional variables. The registry does not report the specific covariates used in the sponsor’s ANCOVA, so it is not possible to reconstruct that adjusted analysis from the record.

What does ANCOVA do?

ANCOVA, or analysis of covariance, compares group outcomes while accounting for one or more covariates in a statistical model. General: When a baseline measurement is included as a covariate, ANCOVA can estimate a treatment-group contrast adjusted for baseline differences. That explanation is general; the registry record does not say which covariates were included, whether baseline dBP was included, or how the analysis handled missing data. It reports the method, a superiority analysis, and a p-value, but not an adjusted effect estimate or confidence interval.

A p-value summarizes how compatible the data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The sponsor’s primary ANCOVA p-value is < 0.001. The unadjusted recalculation has p <0.001. Different methods, adjustments, and rounding can produce different p-values; the registry does not provide sufficient model detail to account for their exact relationship.

Why does variation matter?

The standard deviation describes spread among participant measurements around the group mean. In Phase A, the posted standard deviations are 9.71 for OM 40 and 9.32 for OM/HCTZ 40/12.5. General: Greater variability makes a group mean less precise when other features, including sample size, are held constant. The standard deviation is not the same as the standard error, which describes uncertainty in an estimated mean. The recalculation uses group sizes and standard deviations to estimate uncertainty in the difference.

General: Over-dispersion means observed variability is greater than a model expects. It can make model-based standard errors too small if the model does not account for the extra variability. The registry does not report a specific over-dispersion assessment, and the primary continuous outcome does not itself establish that over-dispersion was present. The concept should not be mistaken for a finding from this trial.

How should Phase B be understood?

Phase B outcomes are presented by response categories for both treatment regimens. The sponsor reports ANCOVA analyses spanning the listed Phase B groups. The dBP analysis reports p < 0.001, while the sBP analysis reports p < 0.001. The registered results do not provide the model’s adjusted estimates or confidence intervals. The recalculated pairwise comparisons are unadjusted and depend on the selected response groups; they should not be assumed to be the sponsor’s ANCOVA contrasts.

General: Analyses defined by a post-baseline response can be harder to interpret causally than the original randomized comparison. Response status is determined after treatment begins and can reflect participant characteristics and treatment response. Unless the analysis plan and model specify how this selection is addressed, comparisons within these categories do not have the same straightforward interpretation as an intention-to-treat comparison of randomized groups. The relevant details are not reported in the registry record.

What is not established by these methods?

The registry does not report the original statistical analysis plan, the original sample-size assumptions, a missing-data method, or the analysis populations. It does not report whether there were interim analyses or how any multiplicity across endpoints and comparisons was handled. These omissions prevent a full audit of model choices and inferential safeguards. General statistical explanations describe how methods commonly work; they do not fill in undocumented trial procedures.

11. Confidence Intervals and Precision

The primary recalculated unadjusted mean difference is -3.1 mmHG, with a 95% confidence interval from -4.473 to -1.727. The interval describes a range of effect values compatible with the observed data under the assumptions of the unadjusted calculation. It does not mean there is a 95% probability that the true effect lies in this particular interval.

Because the interval lies on the negative side of zero, it is consistent with a more negative mean dBP change in the combination group under the stated subtraction order. It conveys both direction and uncertainty, rather than only indicating whether a null value is included. The posted group means are -15.8 and -18.9, and the corresponding group standard deviations are 9.71 and 9.32. Variation among participants means the group averages do not describe every participant’s response.

General: A confidence interval is narrower when an estimate is more precise and wider when the data allow a broader range of plausible effects. Its width depends on factors such as variability, sample size, and the confidence level. The primary endpoint group counts are 282 and 556. The unequal group sizes are relevant context for precision, but the interval itself is the direct summary of uncertainty for the recalculated difference.

The registry reports the sponsor’s ANCOVA p-value but does not report its adjusted estimate or confidence interval. Therefore, the posted adjusted analysis cannot be evaluated for effect-size precision from the registry record. The unadjusted interval should not be relabeled as the ANCOVA interval, and neither interval nor p-value alone establishes clinical importance. The record does not state a threshold for an important difference in dBP.

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 illustrations use the observed effect as a reference and show hypothetical participant requirements under stated assumptions. For these continuous outcomes, the counts are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. These are planning illustrations, not a report of how the original trial was designed.

The 80% power column indicates the number of participants per arm in a hypothetical study that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding hypothetical number for a 90% chance. These are prospective planning quantities, not guarantees that a particular study will reach a result.

Rows for 100%, 75%, and 50% of the observed effect illustrate how required sample size changes when the assumed target effect is smaller than the observed estimate. Smaller effects require more participants to detect with the same power and significance level. For example, the primary comparison’s planning illustration requires 146 participants per arm for 80% power when planning for 100% of the observed effect, and 584 participants per arm when planning for 50% of it. These figures do not establish the trial’s original justification; that justification is not reported in the registry record.

This is not observed power. It is a set of hypothetical planning calculations based on the observed effect and the listed assumptions. The assumptions may differ from the original trial’s design choices, which are not reported in the registry record. Results should therefore be read as sensitivity illustrations about sample size, not as evidence that the completed study was adequately or inadequately powered.

13. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = -3.100; pooled standard deviation σ = 9.453.
2. n = 2 × (1.96 + 0.842)² × 9.453² / -3.100² = 146.0, rounded up to 146 participants per arm for 80% power.

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

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -3.1                      # observed difference in means
sigma <- 9.45288392363327                     # 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(441350)
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 = 146 (80% power), 196 (90% power)
 75% of observed effect: n per arm = 260 (80% power), 348 (90% power)
 50% of observed effect: n per arm = 584 (80% power), 782 (90% power)
power.t.test: 146.9 
Simulated power at n = 146 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 sponsor’s registered primary analysis is an ANCOVA superiority analysis comparing the two Phase A groups, with p < 0.001. The recalculated unadjusted comparison from the posted means and standard deviations gives a mean difference of -3.1 mmHG, a 95% confidence interval from -4.473 to -1.727, and p <0.001. These results point in the same direction regarding evidence of a group difference, but they arise from different analyses.

The recalculation is a simple unadjusted comparison of group summaries. ANCOVA is a model-based analysis that can account for covariates, but the registry does not identify which covariates were used or report the adjusted contrast and its confidence interval. The sponsor’s p-value consequently cannot be used to recover the adjusted effect magnitude or its precision.

The discrepancy indicator for this outcome is false, so the record does not flag a discrepancy between the recalculation and the sponsor’s result. That does not make the analyses identical. The sponsor’s reported analysis is the registered trial analysis; the recalculation is supplementary context based on summary statistics. Differences in statistical method and information available for adjustment should remain explicit when interpreting them.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes, with multiple comparisons among the Phase B response groups. The sponsor reports superiority analyses using ANCOVA for the primary and secondary outcomes. The record does not report a multiplicity strategy, such as an adjustment across outcomes or a sequence specifying which tests were confirmatory. It is therefore unclear whether the reported p-values were intended to control the overall chance of a false-positive finding across all analyses.

General: When several hypotheses are tested, the probability of at least one small p-value by chance can rise. This is why the number and ordering of planned tests matter. The existence of more than one endpoint does not automatically invalidate results, but the inferential meaning of individual p-values depends on the analysis plan and any multiplicity control. Neither is fully described in the registry record.

Missing-data handling is also not reported. The primary endpoint group counts are 282 and 556, whereas the registry’s overall enrollment is 1004. The Phase A safety groups have denominators of 285 and 561. These figures alone do not identify how many participants lacked endpoint measurements, why counts differ, or which analysis population was used. Participant flow, withdrawal reasons, imputation methods, and sensitivity analyses are not reported in the registry record.

The record identifies randomized allocation and reports ANCOVA, but does not state whether the analysis followed an intention-to-treat principle, used a per-protocol population, or applied another population definition. It also does not report the covariates, model diagnostics, or procedures for handling protocol deviations. These omissions limit independent assessment of the robustness of the sponsor’s model-based results. They are not evidence that any specific procedure was or was not performed; the details are simply not reported in the registry record.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteoarthritis (0.8%), erysipeloid (0.8%), anal fissure (0.5%), atrial flutter (0.4%), duodenal ulcer (0.4%).

The registry lists serious adverse event counts and at-risk denominators for several Phase A and Phase B groups. In Phase A, serious adverse events are reported for 4 of 561 in the OM/HCTZ 40/12.5 group and 5 of 285 in the OM 40 group. The listed Phase A deaths are 0 in both groups. Phase B counts are reported separately by response status, so they should not be combined with Phase A counts as though they came from the same comparison period.

The registry lists serious-event terms including Osteoarthritis and Erysipeloid at 0.8%, Anal fissure at 0.5%, and Atrial flutter, Duodenal ulcer, and Syncope at 0.4%. The record does not establish that these terms are specific to one randomized group in the summary of terms. They should not be treated as comparative rates between the original arms.

These figures are descriptive counts, not a complete assessment of safety. The registry does not report a detailed account of event timing, severity beyond the serious-event classification, causal assessment, or a statistical comparison of safety outcomes. Zero deaths in the listed groups does not establish the absence of other risks. Differences in group denominators and the separate Phase B populations also matter when interpreting the counts.

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

The primary result describes an eight-week difference in average sitting dBP change during Phase A. The combination group’s mean change was more negative than the OM 40 group’s mean change, and the unadjusted confidence interval and p-value indicate evidence of a difference under that calculation. The sponsor’s ANCOVA analysis also reports a superiority result. These findings concern the registered blood-pressure endpoint and timeframe only.

The result does not establish how much an individual participant’s dBP would change, what proportion of participants would reach a target, or whether the measured difference is clinically important. The registry gives no threshold for an important change. A group mean can conceal variation in individual responses, and the standard deviations indicate that observations varied around those means.

The findings also do not establish effects on cardiovascular events, mortality, quality of life, long-term blood-pressure control, or outcomes beyond the registry’s stated measures. The trial description includes Phase B treatment changes for insufficiently controlled blood pressure, but the record does not provide a complete account of all planned Phase B treatment results. The registered evidence should not be extended to unreported outcomes or durations.

General: Statistical evidence of a difference and clinical importance are separate questions. The p-value concerns compatibility with a null hypothesis under an analysis, while the effect estimate describes the magnitude and direction of a contrast. Clinical interpretation also depends on context, measurement quality, harms, and the importance of the difference to patients. The registry does not contain all information needed to resolve those broader questions.

The registry identifies randomization and double masking, which are relevant design features for limiting bias, but it does not report enough detail to assess every aspect of trial conduct or analysis. The difference between overall enrollment and endpoint counts is unexplained, and missing-data methods and analysis populations are not reported. Those gaps limit conclusions about completeness and robustness.

18. Why This Trial Matters Statistically

This trial illustrates why an effect estimate, its uncertainty, and the analysis method should be considered together. The primary group means describe the observed average changes, the recalculated mean difference expresses their contrast, and the confidence interval conveys uncertainty around that contrast. The sponsor’s ANCOVA result adds a model-based analysis, but the registry does not report its adjusted estimate or covariates. A p-value alone cannot replace the magnitude and precision information.

It also demonstrates the interpretive distinction between an initial randomized comparison and later analyses grouped by response. Phase A directly addresses the registered primary comparison between randomized treatments. Phase B outcomes are organized by responder status and concern later treatment experience, so their interpretation depends on how those groups were formed and analyzed. The record does not fully describe those details.

Planning illustrations can help show how sample-size requirements depend on the effect chosen for detection. They are not evidence about the original design or the probability that the completed study found a result. The original sample-size assumptions are not reported, while the posted planning calculations use their own stated assumptions.

Finally, the registry contains useful design, outcome, analysis, and safety summaries, but important audit details are absent. The missing analysis populations, model specifications, multiplicity approach, and missing-data procedures limit the extent to which the registered results can be independently reconstructed. Distinguishing what the results show from what the record leaves undocumented is central to sound statistical interpretation.

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.

Several limitations are specific to the available registry record. Although enrollment is recorded as 1004, the primary endpoint groups contain 282 and 556 participants, and the Phase A safety denominators are 285 and 561. The record does not explain these differences or provide a participant-flow account. It is therefore not possible to determine from the registry why endpoint and safety counts differ or how missing observations were handled.

The sponsor’s ANCOVA analyses are reported with p-values but without adjusted effect estimates, confidence intervals, covariate lists, or model diagnostics. The recalculated estimates use posted summary statistics and are unadjusted; they cannot supply the omitted model details. The registry does not report the original analysis plan, the trial’s own sample-size justification, interim analyses, or multiplicity procedures.

The primary endpoint concerns mean dBP change over eight weeks. The record does not report a threshold for clinical importance or the distribution of individual changes. The Phase B results are organized into response groups, but the registry does not fully describe how those groups relate to assignment and treatment changes, nor does it report the planned 40/25 mg results. These limitations constrain interpretation of the later-phase findings.

The safety summary provides serious adverse event counts, denominators, and a list of serious-event terms, but not a full safety analysis or comparative assessment. The registry record does not report enough detail on event timing, attribution, or the statistical approach to safety outcomes. These are limitations of the available record and do not establish that the trial itself lacked such procedures or data.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Olmesartan/HCTZ 40/12.5 mg Combination Therapy Versus Olmesartan Medoxomil 40 mg Monotherapy in Essential Hypertension — NCT00441350.
• Registry record last updated 2021-07-28; status last verified 2009-06.
• Results first posted 2021-07-28.
• 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

NCT00441350 is a completed Phase III randomized, double-masked, parallel-group study sponsored by Menarini Group. It compares OM/HCTZ 40/12.5 with OM 40 in patients with hypertension and describes two sequential phases of eight weeks each.

The primary Phase A outcome is mean trough sitting dBP change from Week 0 to Week 8. The posted group means are -15.8 mmHG for OM 40 and -18.9 mmHG for OM/HCTZ 40/12.5. The recalculated unadjusted mean difference is -3.1 mmHG, with a 95% confidence interval from -4.473 to -1.727. The sponsor reports an ANCOVA superiority analysis with p < 0.001.

The registry also reports Phase B dBP and sBP outcomes and serious adverse event summaries. Important analysis details, including missing-data methods, analysis populations, multiplicity handling, and the original sample-size justification, are not reported in the registry record.