Telmisartan/Amlodipine (80/10) vs. Telmisartan/Amlodipine (40/10) vs. amlodipine10 in Resistant Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Telmisartan/Amlodipine (80/10) vs. Telmisartan/Amlodipine (40/10) vs. amlodipine10 in Resistant Hypertension (NCT00553267), a registered phase 3 study. The primary outcome is Change From Baseline in Trough Seated Diastolic Blood Pressure.

2. Clinical Question

3. Trial Design

The registry describes a phase 3, parallel study with an eight-week treatment comparison. Its official title calls it randomized and double-blind. The listed arms were amlodipine 10mg, telmisartan 40mg with amlodipine 10mg, and telmisartan 80mg with amlodipine 10mg. The brief summary frames the population as patients who fail to respond adequately to six weeks of amlodipine 10mg monotherapy. The record lists hypertension as the condition and 947 as the enrollment.

The stated primary objective was to assess whether either fixed-dose combination was superior to amlodipine 10mg monotherapy in reducing blood pressure at eight weeks. The primary endpoint was change from baseline in trough seated diastolic blood pressure, measured in mmHg. The endpoint timeframe is baseline and end of study, defined as eight weeks or the last value on treatment. The primary analysis population is described as the full analysis set with a baseline trough blood pressure measurement and at least one post-baseline measurement, using last observation carried forward.

The trial is marked completed. Its listed start is 2007-11, and its primary completion is 2008-10. The sponsor is Boehringer Ingelheim. Although the title and summary describe randomization, the record does not state allocation details. It also flags the arms as not a like-for-like control comparison. The detailed basis for that caution is not reported in the registry record, so it cannot be resolved from the registered information alone.

The registry lists ten outcome measures and sixteen analyses. Secondary outcomes include systolic and diastolic blood pressure changes or control measures, response and normality categories, and oedema incidence. The record does not report the planned sample-size justification, a full statistical analysis plan, or detailed information on how participants were assigned to each arm.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using 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 From Baseline in Trough Seated Diastolic Blood Pressure, measured over Baseline and end of study (8 weeks or last value on treatment).

The primary endpoint is change from baseline in trough seated diastolic blood pressure, measured in mmHg. It is a continuous measure: each participant contributes a blood-pressure value, and the analysis describes change between baseline and the end-of-study assessment. “Trough” refers to a measurement taken at the low point of the dosing interval; the registry does not provide further measurement-procedure details. The endpoint timeframe is baseline and the end of study, defined as eight weeks or the last value on treatment.

The registry specifies a least-squares mean as the endpoint parameter and standard error as the dispersion measure. In general, a least-squares mean is a model-based estimate of an average, while a standard error describes the estimate’s statistical precision. The registry record does not report the group estimates or their standard errors, so neither the magnitude of change nor its precision can be assessed from the posted record.

Blood pressure is measured repeatedly in routine clinical assessment, and a continuous change measure retains more information about the size and direction of observed changes than a binary threshold alone. That is a general statistical reason to use a continuous endpoint, not a claim about the choices made in this trial. The registry’s stated objective was to test superiority of each combination against amlodipine 10mg monotherapy. Without posted contrasts or uncertainty estimates, the endpoint definition alone does not establish whether the objective was met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies the primary endpoint as a least-squares mean for a continuous outcome and gives standard error as its dispersion measure. It also describes the population and the use of last observation carried forward. Detailed model specifications, treatment contrasts, test procedures, and decision thresholds for the primary analysis are not reported in the registry record. The following concepts explain how these methods are generally interpreted; they do not fill in unreported trial procedures.

What does a least-squares mean represent?

In general, a least-squares mean is an estimated mean from a statistical model. Unlike a simple arithmetic average, it may account for variables included in that model. The exact interpretation depends on which variables and terms the model contains. Those details are not reported in the registry record, so the extent of any adjustment and the exact estimand cannot be determined. The registry identifies the endpoint parameter but does not provide the resulting least-squares means.

How should standard error be understood?

In general, a standard error describes the sampling uncertainty of an estimate: smaller standard errors indicate greater precision under the assumptions of the analysis. It is not the same as the spread of individual participants’ measurements. A confidence interval combines an estimate with its uncertainty to give a range of values compatible with the data under a stated method. No primary estimates, standard errors, or confidence intervals are reported in the registry record, so the precision of the treatment comparisons cannot be evaluated.

What can a superiority objective establish?

In general, a superiority analysis compares an outcome between groups against a null hypothesis of no difference, using a prespecified method and decision rule. A treatment estimate describes the size and direction of a contrast; a confidence interval describes its uncertainty, and a p-value measures how compatible the data are with a specified null model. These quantities answer related but distinct questions. The registry states a superiority objective but does not report the primary contrasts, p-values, or the detailed testing procedure. The objective is not itself evidence that superiority was demonstrated.

What does the analysis population mean?

The primary endpoint population is described as the full analysis set of patients who had a baseline trough blood pressure measurement and at least one post-baseline trough blood pressure measurement. This criterion makes clear that an available baseline and follow-up measurement were required for inclusion as described. The registry record does not define the full analysis set further, state whether participants were analyzed according to assigned group, or give the number included in each arm. The enrollment of 947 is a trial-level figure and does not supply those analysis counts.

What is last observation carried forward?

Last observation carried forward, or LOCF, uses a participant’s last recorded outcome value as a substitute for a later missing value. In general, this creates a complete value for an analysis point but relies on an assumption that the last observed value is an acceptable stand-in for the unobserved value. If participants’ outcomes would have changed after their last measurement, LOCF can misrepresent that change. The method does not remove uncertainty caused by missing data. The registry identifies LOCF for the primary endpoint but does not report its rationale, the number of values carried forward, or sensitivity analyses using alternative missing-data methods.

Why do allocation details matter?

In general, random allocation can help balance measured and unmeasured characteristics between groups, while concealment and implementation details affect how reliably that protection is achieved. Blinding can reduce some differences in care or assessment, depending on who is blinded and how the study is conducted. The registry title describes the study as randomized and double-blind, but allocation details and the people blinded are not reported in the registry record. The record also flags the arms as not a like-for-like control comparison. That warning should be retained rather than assuming that the comparisons were fully comparable based only on the title.

How should planning illustrations be read?

In general, a sample-size calculation estimates how many participants may be needed under stated assumptions; it does not report how many participants were actually analyzed. The planning illustration described for this trial uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers detecting a stated fraction of the observed effect. Such quantities are planning illustrations, not observed power, and do not establish what the original trial designers intended. The registry does not report its own sample-size justification. Any calculation based on an observed effect is also conditional on the estimate used as its input and should not be mistaken for an independent result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Amlodipine 10mg", "Telmisartan 40mg and Amlodipine 10mg", "Telmisartan 80mg and Amlodipine 10mg")
n   <- c(305, 306, 310)
m   <- c(-6.48, -9.24, -9.33)
sp  <- c(0.45, 0.45, 0.45)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Amlodipine 10mg  305  -6.480  7.859  -7.366  -5.594
CARM  Telmisartan 40mg and Amlodipine 10mg  306  -9.240  7.872  -10.125  -8.355
CARM  Telmisartan 80mg and Amlodipine 10mg  310  -9.330  7.923  -10.215  -8.445

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ten outcome measures and sixteen analyses. The primary endpoint is identified as change from baseline in trough seated diastolic blood pressure; the secondary outcomes include additional systolic and diastolic blood pressure measures, response and control categories, normality classes, and oedema incidence. Listing multiple outcomes and analyses raises a general statistical issue: when many hypotheses are tested, the chance of at least one apparently positive result can increase unless the analysis plan accounts for multiplicity. The registry record does not report whether an adjustment was used, which outcomes were included in any adjustment, or how the analyses were ordered or prioritized.

The record identifies the primary analysis population as participants with a baseline trough blood pressure measurement and at least one post-baseline measurement, using last observation carried forward. It does not report the number of participants excluded from that population, the amount or pattern of missing data, the numbers analyzed by group, or reasons for missing measurements. It also does not report whether analyses using other assumptions about missing values were conducted. Consequently, the possible influence of missingness and LOCF on the primary estimate cannot be quantified.

The protocol’s statistical analysis plan, interim-analysis procedures, and sample-size justification are not reported in the registry record. Enrollment is listed as 947, but the allocation of that enrollment across groups and the resulting endpoint analysis counts are not stated. The planning assumptions described for sample-size illustrations do not substitute for the trial’s own design justification or analysis plan.

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

The registry record describes a study intended to compare two telmisartan/amlodipine combinations with amlodipine 10mg monotherapy in patients whose response to that monotherapy was inadequate. It identifies a clinically interpretable continuous primary endpoint: change from baseline in trough seated diastolic blood pressure at the end of the eight-week study or the last value on treatment. These design details establish what the trial set out to assess, not what the comparison found.

The primary treatment-group results are not reported in the registry record. There are no posted group estimates, between-group differences, confidence intervals, or p-values for the primary endpoint in the registry entries. It is therefore not possible to describe the size, direction, or statistical precision of the primary comparison, or to state whether the superiority objective was met. The same caution applies to secondary outcomes: their names are listed, but their results are not reported.

General interpretation of a continuous outcome distinguishes the estimated average change from uncertainty around that estimate. A narrow confidence interval can indicate greater precision than a wide one, but neither the interval nor the estimate is available for this endpoint. A statistical test, if reported, would also need interpretation alongside the effect estimate and uncertainty; a test result alone would not describe the magnitude of the observed change.

The adverse-event record gives affected-participant counts but does not report the numbers at risk for those counts. Consequently, event rates and comparative rates cannot be calculated from the posted entries. The recorded serious-event terms and percentages should be read as registry entries, not as proof of a treatment-related cause or a between-group safety difference.

More broadly, the record’s description of randomization and blinding is accompanied by a warning that the arms are not a like-for-like control comparison, while allocation details are not stated. That limitation, the missing outcome estimates, and incomplete information on missingness and multiplicity restrict what can be concluded from the registry record. The design question can be described; the numerical treatment effect cannot.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly stated endpoint and a reported treatment estimate are both needed for statistical interpretation. The registry identifies a continuous primary outcome, change from baseline in trough seated diastolic blood pressure, and names the comparison of interest: each telmisartan/amlodipine combination against amlodipine 10mg monotherapy. Yet without group estimates and uncertainty measures, the central statistical result cannot be evaluated. A detailed endpoint definition cannot take the place of the result itself.

The record also distinguishes several layers that are often conflated. Enrollment of 947 is not the same as the number in the primary analysis. The primary population requires a baseline and at least one post-baseline measurement, and the endpoint description specifies LOCF. Without analysis counts or missing-data summaries, readers cannot assess how the analyzed population relates to enrollment or how much imputation was used.

Multiplicity is another important issue because the record lists ten outcome measures and sixteen analyses. Those counts alone do not establish that multiplicity was or was not handled; the analysis strategy is not reported in the registry record. Likewise, a sample-size illustration based on an observed effect is not a substitute for a documented prospective sample-size justification and is not observed power.

Finally, the registry calls the study randomized and double-blind but does not state allocation details, and it flags the arms as not a like-for-like control comparison. This makes transparent reporting of design and comparative estimates especially important. The record is useful for understanding the planned question and endpoint, while also showing the limits of interpreting a study when its principal results and key analysis details are not reported.

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 most consequential limitation for interpreting this trial from the registry record is that the primary endpoint results are not reported. No group-level least-squares means, standard errors, treatment contrasts, confidence intervals, or p-values are available. Without those values, there is no basis for describing the observed treatment effect or its precision. Secondary outcome results are also not reported in the registry record.

Several design and analysis details are missing. Although the study is described as randomized and double-blind, allocation procedures and the identities of those blinded are not stated. The registry explicitly flags the arms as not a like-for-like control comparison, but does not explain the basis for that warning. The full statistical model, covariates, contrast definitions, testing hierarchy, and multiplicity approach are not reported. The trial’s sample-size justification and any interim analyses are not reported in the registry record.

The endpoint population is defined by the availability of baseline and at least one post-baseline measurement, with LOCF used, but group-specific analysis counts and missing-data quantities are not given. The record does not report the extent of LOCF use, reasons for missingness, or sensitivity analyses. Enrollment of 947 therefore does not establish how many participants contributed to the primary analysis.

For adverse events, the listed affected-participant counts lack corresponding numbers at risk. Rates and comparative risk estimates cannot be inferred from counts alone. The record’s adverse-event entries also do not establish causality. These limitations concern what can be interpreted from the registry record; they do not establish that the unreported analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Telmisartan/Amlodipine (80/10) vs. Telmisartan/Amlodipine (40/10) vs. amlodipine10 in Resistant Hypertension — NCT00553267.
• Registry record last updated 2014-02-13; status last verified 2013-12.
• Results first posted 2009-12-22.
• 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

NCT00553267 is a completed phase 3, parallel study sponsored by Boehringer Ingelheim. The registry describes an eight-week randomized, double-blind comparison in hypertension, with enrollment of 947. The listed groups received amlodipine 10mg, telmisartan 40mg plus amlodipine 10mg, or telmisartan 80mg plus amlodipine 10mg. The record lists a start of 2007-11 and primary completion of 2008-10.

The primary endpoint was change from baseline in trough seated diastolic blood pressure, measured in mmHg, using a least-squares mean and standard error. The described primary population required baseline and at least one post-baseline trough blood pressure measurement, with last observation carried forward. The registry does not report primary outcome estimates or their uncertainty. It lists ten outcome measures and sixteen analyses, but the multiplicity approach and detailed statistical plan are not reported. Allocation details are not stated, and the record flags the groups as not a like-for-like control comparison.