Add-on to Micamlo BP Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Add-on to Micamlo BP Trial (NCT01975246), a randomized phase 3 study. The primary outcome is Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period..

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, active-controlled, parallel-group phase 3 trial. It was multi-centre and compared two treatment groups. The trial is marked completed. The registry lists enrollment as 309. That enrollment entry should not be confused with the analysis counts reported for individual outcomes: the primary full analysis set required specified blood pressure measurements, and the posted group counts for that outcome are reported separately.

The study had an open-label run-in lasting 6 weeks, during which participants took telmisartan 80 mg and amlodipine 5 mg. The trial summary says patients were assigned to one of the two groups after this run-in, and the double-blind comparison lasted 8 weeks. In one group, hydrochlorothiazide 12.5 mg was added; in the other, a matching placebo was used with telmisartan and amlodipine. The registry identifies the treatment combinations but does not report further details about how random assignment was generated or concealed.

The registry lists the start as 2013-11 and primary completion as 2014-06. Its primary outcome was change from baseline in mean seated diastolic blood pressure at trough after the double-blind period. Secondary outcomes included change in seated systolic blood pressure and the proportion meeting the stated seated blood pressure thresholds. The trial design makes the primary comparison an assessment of the assigned regimens during the defined double-blind period in patients who had already received the background combination during run-in. The record does not report the original sample-size justification or the detailed statistical analysis plan.

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: This study is randomised, double-blind, active-control, parallel-group comparison

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS): This analysis set was, conforming to the intent-to-treat principle, defined as all patients i) included in the treated set; and ii) taking measurements of seated DBP at reference baseline and at 1 or more time points during the double-blind period.

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.

Population: Treated Set (TS): The treated set consisted of all patients who were randomised to the double-blind period and took at least 1 dose of the randomised treatment.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period., measured over baseline and week 8.

The primary endpoint was change from baseline in mean seated diastolic blood pressure at trough after 8 weeks of the double-blind period, measured in mmHg. Diastolic blood pressure is the lower of the two blood pressure readings. The registry specifies measurements after participants had rested in a seated position for approximately 5 minutes. Blood pressure was measured 3 times at approximately 2-minute intervals, and the mean of those measurements was used as the endpoint.

Change from baseline expresses the follow-up measurement relative to the participant’s baseline value. A more negative group mean represents a greater average reduction from baseline. The endpoint is continuous, so it retains information about the measured amount of change rather than reducing the primary assessment to whether a participant crossed a threshold. The registry identifies the assessment time as baseline and week 8.

The primary analysis population was the full analysis set. The record defines this as patients included in the treated set who had seated diastolic blood pressure measurements at reference baseline and at 1 or more time points during the double-blind period. This definition is intended to follow the intent-to-treat principle while requiring outcome measurements. The precise handling of measurements that were missing, and whether any additional imputation or sensitivity analyses were used, are not reported in the registry record.

7. Results Posted in the Registry

• Telmisartan+Amlodipine: mean -4.50 versus -8.40 on control; difference 3.90 (95% CI 2.51 to 5.29), standardized effect d = 0.63; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period.

• 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:
  • Telmisartan+Amlodipine: mean -6.90 versus -12.30 on control; difference 5.40 (95% CI 3.18 to 7.62), standardized effect d = 0.54; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Telmisartan+Amlodipine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The Proportion of Patients With DBP<90 mmHg and SBP<140 mmHg as Seated Blood Pressure at Trough After 8 Weeks of the Double-blind Period

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Telmisartan+Amlodipine: 36.9% (59/160) versus 51.7% (76/147) on control; risk difference -14.8 percentage points (95% CI -25.8 to -3.8), risk ratio 0.71 (0.55–0.92); unadjusted two-proportion z-test p = 0.009.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Telmisartan+Amlodipine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the secondary outcomes, the overall direction is consistent with the primary result: the group assigned hydrochlorothiazide had a greater average reduction in blood pressure and a larger proportion meeting the posted combined threshold. This pattern offers supporting context across related measurements, but it does not turn secondary outcomes into additional primary endpoints. The primary question remains the comparison of change in mean seated diastolic blood pressure.

The secondary endpoints address different features of blood pressure. The systolic outcome is another continuous change measure, while the combined threshold outcome reduces measurements to whether both stated cutoffs are met. Continuous outcomes preserve the amount of change; threshold outcomes can be easier to interpret as a proportion but discard differences within each category. Results across these measures can therefore be directionally coherent without being redundant or interchangeable.

The registry reports p-values and model-based estimates for the secondary outcomes, but does not report whether a multiplicity adjustment, gatekeeping procedure, or ordered testing plan was used. When several outcomes are examined, the chance of at least one apparently strong result can increase if each is assessed without adjustment. That is a general concern, not evidence that the trial’s results are false. It means the secondary findings carry less inferential weight when their relationship to a prespecified testing strategy is unknown.

The secondary findings can be read as evidence that the primary pattern is not limited to the diastolic measure alone, while retaining caution about their statistical status. Their strength depends on prespecification, missing-data handling, model details, and multiplicity procedures, which are not reported in the registry record. They also pertain to the same study population and follow-up period, so they do not independently establish consistency across other populations or durations.

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

• Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period.
• The Proportion of Patients With DBP<90 mmHg and SBP<140 mmHg as Seated Blood Pressure at Trough After 8 Weeks of the Double-blind Period

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference represent?

The primary endpoint is continuous, and the posted group summaries are means with standard errors. A mean summarizes the group’s average change from baseline. A standard error describes the estimated precision of that mean, rather than the spread of individual participants’ measurements. The posted standard error is 0.5 mmHg in each group. It should not be read as a standard deviation or as a range containing most individual outcomes.

The simple comparison is an unadjusted difference between the posted group means. Its orientation matters: subtracting one group mean from the other changes the sign, not the underlying comparison. The recalculated estimate is 3.9 mmHg when expressed as the comparator group’s change minus the hydrochlorothiazide group’s change. The reported ANCOVA estimate is -3.9 mmHg, consistent in direction when expressed in the opposite order. The registry reports the sponsor’s method as ANCOVA and its parameter as a mean difference in final values. Details of the ANCOVA covariates and model specification are not reported in the registry record.

What does a confidence interval communicate?

In general, a confidence interval is a range of values generated by a statistical procedure that reflects uncertainty in an estimate. Its width depends on the estimate’s precision and the assumptions of the method. A narrow interval indicates greater precision than a wide interval, all else being equal. A 95% confidence interval is not a statement that there is a 95% probability that a fixed, true effect lies within the particular interval. Rather, the confidence level describes the long-run coverage of the procedure under its assumptions.

For the recalculated primary contrast, the 95% interval is 2.514 to 5.286 mmHg. The sponsor reports a 95% interval from -5.3 to -2.4 for the oppositely ordered ANCOVA contrast. These intervals are not identical estimates from identical analyses: one is a simple recalculation from posted change summaries and the other is the reported ANCOVA analysis of final values. They point in the same direction after accounting for contrast order. The registry record does not provide enough detail to reproduce the sponsor’s model.

How should p-values be read?

In general, a p-value is calculated under a null hypothesis and specified statistical assumptions. It describes how unusual the observed result, or a result more extreme, would be if that null model were correct. A small p-value is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. For the primary outcome, the unadjusted recalculated p-value is <0.001, and the sponsor reports p < 0.001. The distinct values reflect the analyses reported, not a contradiction about the direction of the primary result.

Why can an unadjusted recalculation differ from the sponsor’s analysis?

The recalculation uses posted group-level summaries and estimates a simple unadjusted comparison. A trial’s own analysis may use a model, covariate adjustment, or other specifications. ANCOVA is a regression approach that compares outcomes while accounting for modelled covariates; the exact covariates and implementation are not given in the registry record. The sponsor’s reported analysis therefore remains the trial’s reported analysis, while the recalculation is a transparent comparison based on the summary statistics. In this record the discrepancy flag is false, and the two estimates are consistent in direction after allowing for contrast order.

Why does over-dispersion matter in general?

For binary outcomes, a binomial model assumes a particular relationship between the mean event probability and its variance. Over-dispersion means the observed variability is greater than that model expects. If not accommodated, uncertainty estimates can be too small and tests can appear more precise than warranted. This is a general statistical consideration; the registry record does not report whether over-dispersion was assessed or whether it affected any analysis in this trial. The posted binary secondary result is described as a logistic regression analysis, but the record does not give further model diagnostics.

What do the outcome summaries leave unknown?

Summary statistics do not show the full participant-level distribution, the pattern of missing measurements, or how individual outcomes varied over time. The primary full analysis set definition specifies which participants could enter that analysis, but the registry record does not report detailed missing-data methods. It also does not report whether there were interim analyses, how the primary analysis was prespecified, or how multiplicity across outcomes was handled. Those omissions limit independent assessment of all analysis choices and the strength of claims based on secondary outcomes.

11. Confidence Intervals and Precision

The primary group means have standard errors of 0.5 mmHg in both groups. These standard errors concern the precision of each reported mean; they do not describe the spread of individual blood pressure changes. The recalculated difference between groups is 3.9 mmHg, with a 95% confidence interval from 2.514 to 5.286 mmHg. This interval expresses uncertainty around the simple, unadjusted contrast calculated from the posted summaries.

The sponsor’s ANCOVA estimate is -3.9 mmHg, with a 95% confidence interval from -5.3 to -2.4. It uses the reverse contrast orientation and a different analysis form, so the sign and endpoints should be read in that context. Both reported intervals lie in the direction of a larger reduction for the group assigned hydrochlorothiazide. Their widths indicate that the estimate is not a single exact value; a range of differences is compatible with the analyses under their respective assumptions.

In general, confidence intervals provide more information about precision than a p-value alone because they give an estimated range of effect sizes. They do not account automatically for every concern, such as outcome missingness, selection effects, or uncertainty in the analysis plan. The registry record does not report the sponsor’s full model specification, which limits assessment of how its interval was constructed. Nor does the record report sensitivity analyses that would show how robust the estimate is to alternative missing-data assumptions or model choices.

The secondary continuous endpoint also has a reported interval for its recalculated contrast, and the binary endpoint has intervals for its arm proportions and reported comparison measures. These secondary intervals should be interpreted with attention to the methods and multiplicity issue: precision for one endpoint does not establish that it was the only inferential comparison considered. The posted record does not state whether confidence intervals for the outcome set were adjusted for multiple testing.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants and not total events. The table uses the observed effect as a reference and illustrates planning for 100%, 75%, or 50% of that effect. For example, the primary-outcome row for planning for 75% of the observed effect gives 71 participants per arm for 80% power and 95 participants per arm for 90% power. These are planning illustrations, not the trial’s reported enrollment or outcome-analysis counts.

The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the stated fraction of the observed effect as the effect to detect. The 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the specified effect under those assumptions if the effect exists. The 90% power column makes the corresponding planning calculation for a 90% chance. Higher target power generally requires a larger planned sample under otherwise similar assumptions.

Smaller target effects require more participants because a smaller group difference is harder to distinguish from random variation. For the primary endpoint, planning for 50% of the observed effect gives 159 participants per arm for 80% power and 213 participants per arm for 90% power, compared with smaller figures when planning for the full observed effect. The figures vary by endpoint because the observed effect and outcome variability differ.

This is not observed power. It is a planning illustration based on the observed effect, not a reconstruction of the trial’s original design calculation. The original sample-size assumptions and justification are not reported in the registry record. The sample-size figures therefore should not be used to infer that the trial was prospectively designed around the observed result.

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 = 3.900; pooled standard deviation σ = 6.200.
2. n = 2 × (1.96 + 0.842)² × 6.200² / 3.900² = 39.7, rounded up to 40 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 <- 3.9                      # observed difference in means
sigma <- 6.20034372394644                     # 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(1975246)
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 = 40 (80% power), 54 (90% power)
 75% of observed effect: n per arm = 71 (80% power), 95 (90% power)
 50% of observed effect: n per arm = 159 (80% power), 213 (90% power)
power.t.test: 40.7 
Simulated power at n = 40 per arm: 0.791 (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 reports an ANCOVA comparison for the primary outcome: a mean difference in final values of -3.9 mmHg, with a 95% confidence interval from -5.3 to -2.4 and p < 0.001. The recalculation from posted change summaries gives a difference of 3.9 mmHg, with a 95% confidence interval from 2.514 to 5.286 and an unadjusted p-value of <0.001. The sign changes because the two estimates express the group contrast in opposite orders. When the group order is aligned, both indicate a larger reduction in the group assigned hydrochlorothiazide.

The approaches are related but not interchangeable. The recalculation is a simple unadjusted comparison of posted group-level changes. The sponsor’s reported result uses ANCOVA and is labelled as a comparison of final values. The registry record does not identify the covariates or give enough detail to reproduce that model. The sponsor analysis is the trial’s own reported analysis; the recalculation is an additional descriptive check based on the posted summaries. The discrepancy flag is false, so there is no flagged conflict requiring a precedence judgment between results.

The sponsor also reports ANCOVA for the secondary continuous outcome and logistic regression for the binary outcome. These model-based results should be distinguished from simple recalculations. In particular, a model estimate may use assumptions or adjustments that cannot be recovered from marginal summary statistics alone. The registry record does not provide a complete analysis plan or full model specifications, so interpretation should remain tied to the methods and results actually reported.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes. It reports analyses for these measures, but does not report whether the outcomes were arranged in a hierarchy, whether testing proceeded in a prespecified order, or whether p-values and confidence intervals were adjusted for multiple comparisons. The multiplicity procedure, if any, is not reported in the registry record. Consequently, the primary result has a clearer designated role than the secondary findings, which should be interpreted as supportive rather than as independent confirmatory claims unless additional analysis-plan information is available.

The registry defines the primary full analysis set as participants included in the treated set who had seated diastolic blood pressure measurements at reference baseline and at 1 or more time points during the double-blind period. This definition gives useful information about who could contribute to the endpoint analysis, but it does not fully describe the disposition of participants or the availability of measurements at each assessment. The record does not report detailed reasons for missing data, the amount of missingness by group, or whether imputation was used.

Methods for handling missing outcomes can affect estimates, particularly if missingness differs between groups or relates to participants’ outcomes. In general, sensitivity analyses can help assess how conclusions vary under different assumptions. Whether such analyses were conducted is not reported in the registry record. The record also does not report the analysis population used for every secondary endpoint in the same detail as it reports the primary population.

The sponsor identifies ANCOVA for continuous outcomes and logistic regression for the binary outcome. Further details such as model covariates, assumptions, diagnostics, and the statistical analysis plan are not reported in the registry record. Interim analyses and any related statistical procedures are also not reported. These gaps do not negate the posted results, but they limit independent evaluation of prespecification, multiplicity control, missing-data assumptions, and the precise construction of model-based estimates.

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 non-serious adverse event terms

For serious adverse events, the registry reports 0 affected among 149 at risk in the group assigned telmisartan, amlodipine, and hydrochlorothiazide, and 0 affected among 160 at risk in the telmisartan-and-amlodipine group. These are the posted counts during the recorded safety assessment; they should be read as counts within the stated at-risk groups, not as proof that serious adverse events cannot occur.

The registry provides no serious adverse event terms because the listed counts are zero. Death counts are recorded as null for both groups, so deaths are not reported in the registry record. A null entry should not be interpreted as a confirmed zero. The record also lists other adverse events, but those are not serious adverse event counts and should not be conflated with them.

Safety counts are descriptive. They do not, by themselves, establish comparative safety or exclude uncommon harms, especially over a limited study period. The trial’s double-blind period lasted 8 weeks, and the registry record does not provide further detail about longer-term safety follow-up or how adverse events were collected and classified.

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

The posted results show that, during the 8-week double-blind period, the group assigned hydrochlorothiazide with telmisartan and amlodipine had a larger average reduction from baseline in seated diastolic blood pressure than the group assigned telmisartan and amlodipine with matching placebo. The sponsor’s reported ANCOVA result and the simple recalculation from posted summaries agree in direction when their contrast order is taken into account. The secondary outcomes show an overall pattern in the same direction.

That description is limited to the outcomes, population, treatment assignments, and follow-up recorded for this trial. Participants had hypertension and had not responded adequately to the background combination, with the trial summary describing a run-in on that combination before assignment. The results therefore do not automatically generalize to people with different treatment histories, other patient groups, or other durations. The registry record does not provide evidence about outcomes beyond the stated trial period.

A statistically distinct group comparison is not the same as a guarantee of an individual response. Group averages do not describe what happened to every participant, and a confidence interval does not eliminate uncertainty. The findings also do not establish the balance of benefits and harms for an individual or replace clinical judgment. The posted serious adverse event counts are limited observations over the recorded period; they cannot rule out events that were not observed or reported.

The registry record does not report all details needed to evaluate the analysis independently, including the full statistical analysis plan, multiplicity handling, and detailed missing-data methods. The findings should therefore be read as the trial’s reported evidence for its defined comparison, with the primary outcome carrying the clearest inferential role and secondary results interpreted more cautiously.

18. Why This Trial Matters Statistically

This trial illustrates how a clinical comparison can be framed around a continuous outcome and a defined treatment contrast. The primary endpoint uses repeated seated blood pressure measurements and takes their mean, rather than relying on a single reading. Averaging repeated measurements can reduce the influence of moment-to-moment measurement variation; this is a general statistical rationale, while the measurement procedure itself is specified in the registry record.

The distinction between a group’s change and the difference between groups is important. Both primary group means are reductions from baseline, but the comparative question concerns how far those average changes differ. Contrast order determines the sign of a reported difference, as illustrated by the opposite signs of the sponsor’s estimate and the simple recalculation. Reading the group labels and method alongside the sign prevents a directional misinterpretation.

The record also illustrates why effect estimates and uncertainty intervals are more informative than a p-value alone. The estimate describes the scale and direction of the contrast, while its interval conveys precision under the analysis assumptions. A model-based sponsor result and a simple unadjusted calculation can be compared as complementary descriptions, provided their methods and contrast orientations are made explicit.

Finally, secondary outcomes and sample-size planning require context. Related endpoint patterns may support a coherent interpretation, but unreported multiplicity procedures affect how strongly secondary p-values can be treated as confirmatory. Planning illustrations based on the observed effect are not a substitute for the original design justification and are not observed power. These distinctions help separate what the registry reports 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 analysis population is defined by treatment status and availability of baseline and follow-up measurements, but the registry record does not provide detailed missing-data counts, reasons for missingness, or the methods used to address missing measurements. It is therefore not possible to assess from this record alone whether the analyzed participants differed from those without qualifying measurements or how alternative missing-data assumptions might affect the estimate.

The sponsor reports ANCOVA for the primary outcome, but the record does not specify the model covariates or provide enough detail for independent reproduction. The recalculation uses aggregate summaries and is not a substitute for participant-level analysis. The registry also does not report the statistical analysis plan, any interim analyses, or the multiplicity procedure, leaving uncertainty about prespecification and the inferential status of secondary results.

The primary endpoint is measured at the end of an 8-week double-blind period after an open-label run-in on the background combination. The record does not establish how the results would apply beyond that population and timeframe. It also does not report longer-term outcome results. The registry’s serious adverse event entries show no affected participants in the listed at-risk groups, but death entries are null and thus are not reported as counts. These entries do not provide a complete assessment of all possible safety outcomes.

The registry lists enrollment as 309, while endpoint analysis counts are presented for the individual groups and outcomes. The record does not provide enough information in the registry record to reconcile enrollment with every analysis population. The original sample-size justification is also not reported; planning illustrations based on the observed effect cannot fill that gap.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Add-on to Micamlo BP Trial — NCT01975246.
• Registry record last updated 2016-11-29; status last verified 2016-10.
• Results first posted 2016-11-29.
• 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

The registry record describes a completed, randomized, double-blind, parallel-group phase 3 trial in patients with hypertension who did not respond adequately to telmisartan and amlodipine. Following a 6-week open-label run-in, the study compared adding hydrochlorothiazide 12.5 mg with continuing the background combination alongside matching placebo during an 8-week double-blind period.

The primary outcome was change from baseline in mean seated diastolic blood pressure at trough. The posted group means were -8.4 mmHg and -4.5 mmHg, with a recalculated difference of 3.9 mmHg in the comparator-minus-hydrochlorothiazide orientation. The sponsor’s ANCOVA result expresses the contrast in the opposite direction and supports the same directional interpretation. Secondary outcomes show a broadly consistent pattern, subject to uncertainty about multiplicity and analysis details.

The record does not report the original sample-size justification, detailed missing-data methods, or complete model specifications. Those limits matter when interpreting precision and the secondary findings.