A Comparative Study Between Amlodipine 10mg And 5mg With Hypertension For Whom 5mg Is Insufficient: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Comparative Study Between Amlodipine 10mg And 5mg With Hypertension For Whom 5mg Is Insufficient (NCT00415623), a randomized phase 3 study. The primary outcome is Change in Systolic Blood Pressure (SBP) From Baseline to Week 8.

2. Clinical Question

3. Trial Design

The registry describes NCT00415623 as a randomized, double-blind, parallel-group phase 3 study. It compared amlodipine 10 mg with amlodipine 5 mg in patients with essential hypertension for whom 5 mg was insufficiently effective. The treatment period described for the primary assessment was 8 weeks. The registry lists 305 participants as enrolled and records the trial as completed.

The recorded start was 2007-01, and primary completion was 2007-10. The primary analysis used the Full Analysis Set with Last Observation Carried Forward. The arm-level primary results list 151 participants for amlodipine 5 mg and 150 for amlodipine 10 mg. The registry does not explain the relationship between these analysis counts and the enrollment total, and does not report a participant flow account in the registry record for this summary.

Random allocation and double masking are stated, but the method used to generate the allocation sequence, conceal allocation, or implement masking is not reported in the registry record. The trial is described as parallel-group; details about visit schedules beyond the week 6 and week 8 outcomes, treatment adherence, and concomitant care are not reported in the registry record. The arm descriptions contain no additional detail beyond the dose labels. The registry identifies Pfizer's Upjohn as having merged with Mylan to form Viatris Inc.

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: Consent was taken from 414 patients, 356 patients who met the screening criteria received amlodipine 5 mg. After the 8 weeks of screening treatment, patients who met the entry criteria for double-blind period were randomized to either the amlodipine 10 mg group or the amlodipine 5 mg group at a ratio of 1:1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set, Last Observation Carried Forward

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 Systolic Blood Pressure (SBP) From Baseline to Week 8, measured over Baseline to Week 8.

The primary endpoint is the change in trough systolic blood pressure (SBP) from baseline to week 8, expressed as a least-squares mean in mmHg. It measures the average change in the recorded blood-pressure measure over the treatment period, with negative values indicating a decrease from baseline. The word trough identifies the measurement as a trough SBP assessment; the exact timing and measurement procedures are not reported in the registry record.

Change from baseline is useful for describing how an outcome shifts during follow-up while retaining a participant's baseline measurement as the reference. Comparing changes between randomized groups focuses the question on the difference in mean change associated with assignment to the two dose groups, rather than describing either group's endpoint in isolation. General statistical context: a least-squares mean is a model-based estimate of a group mean, and its interpretation depends on the model and covariates used. The registry names ANCOVA for the comparison but does not report the full model specification or covariates.

The primary outcome is listed as the mean change in trough SBP, with a 95% confidence interval for each arm and for the reported between-arm comparison. The registry identifies the primary assessment timeframe as baseline to week 8.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported ANCOVA comparison estimate?

The primary comparison is reported as an analysis of covariance (ANCOVA), with a mean difference in final values. ANCOVA is a regression-based method that can compare group outcomes while accounting for specified covariates. General statistical context: adjusting for baseline outcome values can improve precision when baseline measurements are related to follow-up measurements. However, the registry does not report the covariates, model terms, assumptions, or missing-data handling within the ANCOVA itself. It is therefore safest to interpret the published estimate as the sponsor-reported model-based comparison rather than reconstructing its exact specification.

The arm estimates are least-squares means, which are model-based rather than necessarily simple arithmetic averages. Their confidence intervals describe precision around each estimated mean under the analysis model. The between-group mean difference addresses the comparative question more directly than either arm's change considered alone. The registry reports the comparative estimate as -6.7 mmHg, with a 95% confidence interval from -9.0 to -4.4 mmHg and p < 0.001.

How should confidence intervals and p-values be read?

General explanation: a confidence interval communicates both the estimated direction and the range of values reasonably compatible with the observed data and model. A narrower interval indicates greater precision than a wider interval, all else equal. It is not a range containing a guaranteed proportion of individual participants' responses, and it does not describe individual variation in the same way as a standard deviation.

A p-value evaluates how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Here, the reported p-value is p < 0.001. The comparison's interval and p-value should be read alongside the estimated difference and its units, rather than as stand-alone evidence of importance.

What do the binary secondary comparisons describe?

The registry reports counts for three binary secondary outcomes. The associated analyses include logistic regression results expressed as odds ratios, and the posted recalculations include unadjusted risk differences and p-values. An odds ratio compares the odds of meeting the defined outcome between groups; it is not the same quantity as a risk difference, which compares event proportions. General statistical context: odds ratios can be less intuitive to interpret than absolute differences, especially when an outcome is not rare. The registry's definition of the target blood-pressure reduction value is not reported, which limits interpretation of these attainment outcomes.

The recalculated binary comparisons are unadjusted comparisons from the posted counts. They are descriptive re-analyses, not substitutes for the registry's logistic regression analyses. For the week 8 target outcome, the recalculated unadjusted p-value is 0.005, while the registry reports an odds ratio of 2.33, a 95% confidence interval from 1.36 to 3.99, and p = 0.002. For achievement at both weeks 6 and 8, the recalculated unadjusted p-value is p < 0.001, while the registry reports an odds ratio of 4.46, a 95% confidence interval from 2.28 to 8.74, and p < 0.001. For the combined target and SBP-decrease outcome at week 8, the recalculated unadjusted p-value is 0.001, while the registry reports an odds ratio of 2.55, a 95% confidence interval from 1.50 to 4.36, and p = 0.001.

General explanation: the methods can yield different estimates and p-values because they target different effect measures and may handle covariates differently. The posted recalculations do not reproduce the logistic regression model. As there is no discrepancy flagged for the primary continuous outcome, the direct interpretation of that endpoint rests on the registry's reported ANCOVA analysis.

What can planning illustrations tell readers?

Sample-size planning illustrations use an observed effect as a reference and explore smaller fractions of that effect. They are not observed power and do not show the trial's actual design justification. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is the stated fraction of the observed effect. General statistical context: planning estimates depend on assumptions about the effect size, outcome variability, allocation, and analysis. If a future study is designed around a smaller effect, it generally requires more participants than a plan based on a larger effect, all else equal. The trial's own sample-size justification is not reported in the registry record.

The registry does not report an interim analysis plan, a formal statistical analysis plan, or an adjustment strategy for multiple comparisons. Those omissions matter when interpreting multiple endpoints and p-values: the record does not establish which secondary tests, if any, were intended to be confirmatory.

10. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is an ANCOVA comparison of final values. It gives a mean difference of -6.7 mmHg, a 95% confidence interval from -9.0 to -4.4 mmHg, and p < 0.001. The reported arm estimates are least-squares mean changes from baseline, while the between-group result is reported as a mean difference in final values. These should not be conflated: the first describes change within each group, and the latter is the registry's direct comparison.

For the binary secondary outcomes, the registry reports logistic regression odds ratios. The posted recalculations use the observed counts to produce unadjusted risk differences and p-values. Those are different analyses and effect measures, so they need not match the sponsor's odds ratios or p-values. For example, the sponsor's reported odds ratio and p-value for the week 8 target outcome are 2.33 and 0.002; the unadjusted recalculated p-value is 0.005. For the other two binary outcomes, both sets of p-values are reported as p < 0.001 or 0.001, while the effect estimates remain on different scales.

No discrepancy is flagged for the primary result. The sponsor's own reported model is therefore the relevant estimate for the primary comparison; the simpler recalculations are useful as an independent descriptive check, not as replacements for the reported adjusted analyses. Model details that would permit full replication are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint: change in SBP from baseline to week 8. It also lists secondary outcomes, including continuous blood-pressure changes, target-attainment measures, and trough plasma concentrations. Nine secondary outcomes are posted, but numerical results are available for only some of them. A testing hierarchy, confirmatory designation for secondary endpoints, and adjustment for multiple comparisons are not reported in the registry record.

Multiplicity matters because repeated statistical tests create more opportunities for small p-values to occur by chance. General statistical context: adjustment procedures can control error rates across a defined family of tests, but their suitability depends on which outcomes and comparisons were planned together. Without a reported testing plan, the secondary p-values should be treated as exploratory or supportive rather than as a set of independently confirmatory findings. An interim-analysis plan and any associated control of repeated testing are not reported in the registry record.

The primary analysis population is described as the Full Analysis Set, with Last Observation Carried Forward. The registry does not report how the Full Analysis Set was defined, the number of missing observations, reasons for missingness, or the timing and pattern of missing data. It also does not describe sensitivity analyses for missing outcomes. General statistical context: Last Observation Carried Forward fills a missing later measurement with an earlier observed value. This approach can be problematic when outcomes change over time or when missingness is related to outcome, and its effect depends on the missing-data process. The record does not provide enough information to assess how well that assumption fits this trial.

The registry gives arm counts for the primary outcome, but does not supply a participant flow account or explain any differences between enrollment and analysis counts. Details of the secondary analysis populations and missing-data procedures are not reported in the registry record. These gaps limit assessment of how robust the reported findings are to exclusions, missing data, and the handling of multiple endpoints.

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

The primary result describes a difference between randomized groups in the week 8 blood-pressure outcome. In the registry's ANCOVA analysis, the estimated mean difference in final values is -6.7 mmHg, with a 95% confidence interval from -9.0 to -4.4 mmHg and p < 0.001. This quantifies the estimated group contrast and its statistical precision under the reported analysis.

It does not establish the size of benefit that an individual participant would experience. The arm-level estimates are group means, and individual responses may differ. Nor does a small p-value establish that the observed contrast is clinically important. The registry does not give a threshold for clinical importance, and this statistical summary does not assess outcomes beyond those recorded in the trial.

The result pertains to patients described as having essential hypertension for whom amlodipine 5 mg was insufficiently effective, and to the 8-week treatment period. It does not establish what happens with longer follow-up, in other populations, or with other treatment regimens. The record identifies randomization and double masking, but does not report enough detail to independently assess the implementation of those procedures.

The primary analysis used Last Observation Carried Forward. Since the amount and pattern of missing data and sensitivity analyses are not reported, the potential effect of missing outcome data cannot be fully evaluated. The posted secondary outcomes show a broadly similar direction for the reported binary comparisons, but the definitions and multiple-testing procedures are incomplete. They should not be interpreted as definitive independent confirmations of the primary result.

General statistical context: a trial result is most informative when considered together with the endpoint definition, analysis population, follow-up duration, precision, missing-data handling, and clinical context. The registry supplies an estimated group comparison and uncertainty interval, but does not report all details needed to assess every assumption or translate the finding into a broader clinical conclusion. No treatment recommendation follows from these statistics alone.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between within-group change and a between-group comparison. Both groups have reported changes from baseline, but the comparative question is answered by the ANCOVA estimate, not by comparing the two arm estimates informally. The reported mean difference, confidence interval, and p-value put the size and precision of that contrast on a common scale.

It also illustrates how outcome scale affects interpretation. The primary endpoint is continuous and expressed in mmHg, while the secondary target-attainment outcomes are binary and are reported as odds ratios by the registry. The recalculations express binary contrasts as unadjusted risk differences. These measures describe different aspects of the data and are not interchangeable, even when they point in the same general direction.

The record further shows why the analysis population and missing-data method matter. The primary result uses the Full Analysis Set and Last Observation Carried Forward, yet the underlying missingness information and sensitivity analyses are not reported. That makes it harder to understand the robustness of the estimate. Similarly, the absence of a multiplicity plan limits how strongly multiple secondary p-values can be interpreted.

Finally, the posted sample-size illustrations should be understood as planning exercises based on observed effects and stated assumptions, not as evidence of the trial's original design rationale or observed power. Separating planning assumptions, sponsor-reported model results, and unadjusted recalculations helps keep each statistic tied to the question it actually answers.

14. 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 registry record leaves important design and analysis details unspecified. It does not report the randomization sequence method, allocation concealment, detailed masking procedures, or full eligibility criteria. It names ANCOVA for the primary comparison but does not identify the model covariates or provide a full analysis plan. As a result, the reported estimate can be interpreted, but its complete analytic specification cannot be independently reconstructed.

The primary follow-up described is 8 weeks. The registry does not provide longer-term outcome data, and the registry entries available for this summary do not report the exact blood-pressure measurement procedures or timing represented by trough. The target blood-pressure reduction value for secondary endpoints is also not defined. Numerical results for several listed secondary outcomes, including some continuous measures and plasma concentrations, are not reported in the registry record.

Missing-data limitations are particularly relevant because the primary analysis used Last Observation Carried Forward. The amount, reasons, and pattern of missing data, as well as sensitivity analyses, are not reported. The relationship between the enrollment count and the arm-level analysis counts is not explained in a participant flow account. These omissions prevent a detailed evaluation of exclusions and missingness.

The registry does not report a multiplicity strategy, interim analyses, or the trial's sample-size justification. Planning illustrations based on observed effects cannot fill those gaps. Finally, although the trial is recorded as randomized and double-blind, the record does not provide procedural details to evaluate how those protections were implemented. These limitations do not negate the posted estimates, but they narrow the conclusions that can be drawn from the registry information alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Comparative Study Between Amlodipine 10mg And 5mg With Hypertension For Whom 5mg Is Insufficient — NCT00415623.
• Registry record last updated 2021-02-11; status last verified 2021-01.
• Results first posted 2008-12-09.
• 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.

18. Record Summary

NCT00415623 is recorded as a completed, randomized, double-blind, parallel-group phase 3 study comparing amlodipine 5 mg with 10 mg in patients with essential hypertension for whom 5 mg was insufficiently effective. The registry lists 305 enrolled participants and an 8-week treatment period for the primary assessment.

The primary endpoint was change in trough SBP from baseline to week 8 in the Full Analysis Set using Last Observation Carried Forward. The registry reports an ANCOVA mean difference in final values of -6.7 mmHg, with a 95% confidence interval from -9.0 to -4.4 mmHg and p < 0.001. Interpretation is limited by missing detail on model specification, missing data, secondary-outcome multiplicity, and participant flow.