The Effect of Spironolactone on Blood Pressure in Type-2 Diabetics With Resistant Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Spironolactone on Blood Pressure in Type-2 Diabetics With Resistant Hypertension (NCT01062763), a randomized phase 3 study. The primary outcome is Change of of Systolic Blood Pressure.

2. Clinical Question

3. Trial Design

The South Danish Hypertension and Diabetes Study, registered as NCT01062763, was a phase 3 randomized parallel-group study. Its status is completed. The registry lists a study start of 2010-03 and a primary completion of 2012-03. The sponsor is Ib Abildgaard Jacobsen. Overall enrollment was 119.

The two intervention groups were addition of spironolactone and addition of placebo. The arm descriptions indicate that spironolactone was added to previous antihypertensive treatment, while placebo was added in the comparator arm. The record identifies the conditions as arterial hypertension, hypertension resistant to conventional therapy, and diabetes mellitus. The study was aimed at people with type-2 diabetes and resistant hypertension.

Allocation is recorded as randomized, masking as quadruple, and the model as parallel. These terms describe broad design features: participants were assigned to concurrent groups, and masking was intended across four roles or parties. The registry record does not identify which specific roles were masked, describe the randomization sequence, or give details about allocation concealment. Further information about treatment dose, duration, adherence, and background antihypertensive regimens is not reported in the registry record.

The primary outcome was a continuous measure: change in systolic blood pressure from baseline to the study end at four months. The registry specifies analysis by intention to treat using last observation carried forward. The endpoint summaries list 57 participants for addition of spironolactone and 55 for placebo. The record does not explain why these endpoint counts do not match overall enrollment. No formal two-arm analysis is posted for this continuous outcome, and the registry record does not report the trial’s sample-size justification or a 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: 163 patints screened. 44 screenfailures due to exclusion criteria as indicated. 119 randomized

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis by intention to treat using LOCF

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Change of of Systolic Blood Pressure, measured over 4 months.

The primary endpoint measures change in systolic blood pressure from the start of the study to the four-month study end. Systolic pressure is the upper value in a blood-pressure measurement; expressing its change in mm Hg allows the outcome to retain the scale of the original measurement. A negative change indicates a decrease from baseline, while a positive change indicates an increase.

Change from baseline is used to describe how the measured outcome differs over the study period. Reporting the mean gives a group-level summary, while a confidence interval communicates uncertainty around that summary. The registry gives a mean change and a 95% confidence interval separately for each arm. These arm-specific intervals concern the mean change within each group; they are not a confidence interval for the difference between randomized groups.

The stated endpoint timeframe is four months, and the outcome population is described as intention to treat using last observation carried forward. This analysis approach is relevant because some participants may not have a measurement at the scheduled endpoint; the registry record does not report how many measurements were missing or how they arose. A between-group contrast is the quantity needed to describe the comparative effect of assignment, but the registry does not report an estimable contrast for this continuous endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous because systolic blood pressure is recorded on a numerical scale. The registry summarizes the outcome using a mean change and a 95% confidence interval for each arm. In general, a mean is a measure of the central location of a group’s observations. A confidence interval describes uncertainty in an estimated quantity under the assumptions of the analysis. It is not a range containing a fixed proportion of individual participants’ measurements, nor does an arm-specific interval directly answer a between-group question.

What does a randomized comparison estimate?

In general, a randomized two-arm analysis compares outcomes according to assigned group. For a change endpoint, the target contrast is the difference between the groups’ mean changes, interpreted with an uncertainty interval and, where planned, a test statistic or p-value. Randomization supports a fair comparison in expectation, but the analysis still needs to estimate the contrast and its uncertainty. The registry record does not report an estimable contrast for this continuous endpoint. The separate arm means and intervals cannot replace that missing comparative result.

The reported arm summaries are -9.6 mm Hg for addition of spironolactone, with a 95% confidence interval from -12.8 to -6.3, and -0.7 mm Hg for placebo, with a 95% confidence interval from -3.3 to 2.0. These values are quoted as posted. No new contrast has been calculated from them. Since there is no reported between-group confidence interval or test, the precision of the comparative effect cannot be assessed from the registry results.

How should the confidence intervals be read?

In general, a confidence interval expresses the sampling uncertainty around an estimate under the method used to construct it. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. The interpretation depends on the estimand: an interval around a group mean change concerns that group’s mean, whereas an interval around a treatment contrast concerns the comparative effect. Here, only the former is posted. The registry does not describe the interval construction method beyond identifying the dispersion as a 95% confidence interval.

In general, a confidence interval that includes zero for a change estimate is compatible with no average change as well as changes in either direction, under the assumptions behind the interval. A confidence interval that excludes zero for an arm’s change concerns that arm’s within-group estimate. Neither fact by itself establishes whether the randomized groups differ. The comparison must be estimated directly; separate intervals should not be treated as a substitute for it.

What does intention to treat using LOCF mean?

The registry describes the primary outcome population as intention to treat using LOCF, or last observation carried forward. In general, intention-to-treat analysis aims to retain participants in the groups to which they were assigned, rather than reclassifying them according to treatment received. LOCF is a method for handling a missing endpoint measurement by carrying a participant’s last recorded measurement forward as the endpoint value. It creates an analyzable value but does not recover an unobserved measurement. Its validity depends on assumptions about how the missing outcome relates to prior measurements and subsequent change.

LOCF can distort estimates when a participant’s outcome would have changed after the last available measurement, or when missingness is related to the outcome. Modern missing-data assessment therefore considers why measurements are absent and whether conclusions change under alternative assumptions. The number and timing of missing observations, reasons for missingness, and sensitivity analyses are not reported in the registry record. The consequences of LOCF for these results therefore cannot be evaluated from the posted information.

What can be said about planning assumptions?

The registry record does not report the trial’s own sample-size justification. A planning illustration based on the observed effect is not the same as a trial design calculation based on a prespecified target effect, and it is not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Such calculations are conditional on those assumptions and should not be read as evidence about the probability that the completed study detected an effect.

In general, power is a property of a design under assumed effects, variability, and analysis conditions. Calculating power after results are known from the observed effect does not provide a useful measure of how persuasive or conclusive the findings are. The registry does not post the illustration values in the record summarized for this analysis, so no participant requirements or power values are stated. The assumptions also do not establish what the investigators used when planning the study.

Why does over-dispersion matter?

For continuous outcomes, an analysis must represent variability in the measurements as well as their average. In general, over-dispersion refers to variability greater than a model assumes. If a model understates variability, standard errors may be too small and confidence intervals too narrow; if variability is modeled appropriately, uncertainty is better calibrated. The registry provides confidence intervals but does not report a separate dispersion estimate or the model used to construct them. It is not possible to determine from the record whether over-dispersion was relevant or how variability was handled.

The registry lists 0 analyses for the posted outcomes, despite giving arm-level summary results for the primary endpoint. The continuous two-arm comparison is specifically identified as not estimable. Thus, the record offers descriptive endpoint summaries but not a formal comparative analysis. It does not report covariate adjustment, a model specification, test statistics, or a prespecified plan for handling multiple outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 1 secondary outcome, Adverse Effects. The primary outcome is change in systolic blood pressure at four months. The record does not provide a hierarchy for interpreting multiple outcomes, a multiplicity adjustment, or a statistical plan for controlling the chance of false-positive findings across analyses. No conclusion about whether such procedures were used outside the posted record can be drawn.

The endpoint population is described as intention to treat using last observation carried forward. In general, this approach carries a participant’s last recorded value forward when the scheduled endpoint measurement is missing. It can keep assigned groups intact, but it relies on assumptions about the unobserved outcome. The registry does not report how many participants lacked endpoint measurements, when measurements were last observed, why data were missing, or whether the missingness differed between arms.

The record also does not describe sensitivity analyses that might show how results change under other missing-data assumptions. The primary endpoint counts are 57 in the spironolactone group and 55 in the placebo group, while total enrollment is 119; reasons for the counts are not reported in the registry record. The registry posts arm-level means and intervals but no estimable two-arm analysis for the continuous endpoint. It does not report a formal test, a comparative interval, or an analysis population beyond the stated intention-to-treat approach using LOCF.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: serious hyperkalemia (1.6%).

The adverse-effect record lists 61 participants at risk for serious adverse events in the addition-of-spironolactone group and 58 in the placebo group. One serious adverse event was reported in the spironolactone group and none in the placebo group. The listed serious event term is Serious hyperkalemia, reported as 1.6%. The registry reports no other adverse events in either group. Death counts are not reported in the registry record.

These counts describe events recorded in the study; they do not establish whether an event was caused by the assigned intervention. The listed denominators are the numbers at risk for adverse-event reporting, not the endpoint-analysis counts. The record does not explain why those denominators differ from the counts reported for the primary outcome. It also does not provide additional detail about event definitions, timing, severity grading beyond the serious classification, or methods for attributing events.

With one serious event in one group and none in the other, the record contains little information for estimating comparative safety precisely. A zero count does not demonstrate that an event cannot occur, and these figures alone do not establish a difference between groups. The registry does not report a formal safety comparison or uncertainty interval for adverse events.

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

The registry reports a mean four-month systolic blood pressure change of -9.6 mm Hg in the addition-of-spironolactone group and -0.7 mm Hg in the placebo group. It reports a 95% confidence interval of -12.8 to -6.3 for the first group and -3.3 to 2.0 for the second. These summaries show the arm-level estimates and their reported uncertainty, but they do not directly estimate the difference between randomized groups.

The primary scientific question is comparative: how did assignment to spironolactone added to existing treatment compare with assignment to placebo added to existing treatment? The registry does not provide an estimable two-arm analysis for this continuous endpoint, nor a comparative effect estimate, confidence interval, or p-value. Consequently, the posted arm-level values do not establish the magnitude or precision of the between-group effect. The separate confidence intervals should not be interpreted as though they were a test of the randomized comparison.

The record describes a randomized, quadruple-masked, parallel phase 3 study, but design labels alone cannot fill in an absent endpoint comparison. Important details about the randomization procedure and masking roles are not reported in the registry record. The endpoint analysis is described as intention to treat using LOCF, but missingness details and sensitivity analyses are not posted. This leaves uncertainty about how missing measurements may have influenced the reported arm summaries.

The adverse-effect information is also limited. One serious adverse event was listed in the spironolactone group and none in the placebo group; the serious term listed was Serious hyperkalemia at 1.6%. These counts do not establish causation or a comparative safety difference, and death counts are not reported in the registry record.

Overall, the registry record documents a clinical question and provides descriptive results for a primary endpoint, but it does not include the formal comparative result needed to answer that question statistically. The findings should be read as posted group summaries, not as proof for or against a treatment effect. Additional protocol, analysis, and follow-up information is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why the distinction between within-group change and a randomized between-group comparison matters. The primary outcome is reported as a mean change in each arm, with a confidence interval for each mean. Those summaries describe the groups separately. The central comparative question, however, concerns the difference in change between assigned groups, and that estimate is not reported as an estimable result in the registry.

It also demonstrates that reporting a confidence interval does not automatically answer every statistical question. The intervals quantify uncertainty around the arm-specific mean changes, not uncertainty around a contrast. Treating them as a substitute for a direct comparison would confuse two distinct estimands. This distinction is important when interpreting clinical trial results, especially when the registry provides descriptive summaries but no formal test or comparative interval.

The record also makes the analysis approach visible: the primary outcome is described as intention to treat using last observation carried forward. That wording indicates how missing endpoint measurements were handled, but it is not enough to assess the consequences. The amount and pattern of missing data, reasons for missingness, and sensitivity analyses are not reported in the registry record. An explicit method label should therefore not be mistaken for a complete account of missing-data uncertainty.

Finally, the study’s planning assumptions and its observed results serve different purposes. A sample-size illustration based on the observed effect is a planning exercise under stated assumptions, not evidence of observed power and not the trial’s own design justification. The trial’s sample-size justification is not reported in the registry record. Keeping those distinctions clear helps prevent descriptive findings, planning calculations, and formal comparative inference from being treated as interchangeable.

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 main limitation for interpreting the primary endpoint is the absence of an estimable two-arm comparison in the registry record. Arm-level means and 95% confidence intervals are posted, but the comparative estimate, its uncertainty, and a formal test are not. This prevents direct assessment of the randomized contrast from the posted results.

The registry does not report the rationale for the endpoint analysis counts of 57 and 55 in relation to total enrollment of 119. It also does not give the number of missing four-month measurements, reasons for missingness, or sensitivity analyses. Because the stated analysis used last observation carried forward, those missing-data details would be important for assessing the robustness of the summaries.

Further statistical details are not reported in the registry record, including the trial’s sample-size justification, a detailed analysis plan, the method used to construct the confidence intervals, any covariate adjustment, and any multiplicity procedure. The record lists 3 outcome measures and 1 secondary outcome, but it does not describe how multiple outcomes were prioritized or interpreted. The randomization procedure and the specific roles covered by quadruple masking are also not described.

Information about the intervention and comparator is limited to adding spironolactone or placebo to previous treatment. Dose, adherence, treatment adjustments, and background regimens are not reported. Safety reporting includes one serious adverse event in the spironolactone group and none in the placebo group, but further event details, a formal comparison, and death counts are not available in the registry record. These gaps limit interpretation of both the comparative efficacy result and the safety profile.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of Spironolactone on Blood Pressure in Type-2 Diabetics With Resistant Hypertension — NCT01062763.
• Registry record last updated 2014-05-08; status last verified 2014-04.
• Results first posted 2014-05-08.
• 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

NCT01062763 is the completed phase 3 South Danish Hypertension and Diabetes Study, sponsored by Ib Abildgaard Jacobsen. The record describes a randomized, quadruple-masked, parallel study with overall enrollment of 119. It compares spironolactone added to previous antihypertensive treatment with placebo added to previous treatment in people with type-2 diabetes and resistant hypertension. The recorded study start is 2010-03, and primary completion is 2012-03.

The primary endpoint is mean change in systolic blood pressure from baseline to four months, analyzed by intention to treat using last observation carried forward. The posted arm-specific means are -9.6 mm Hg for spironolactone and -0.7 mm Hg for placebo, with respective 95% confidence intervals of -12.8 to -6.3 and -3.3 to 2.0. The registry does not report an estimable two-arm comparison for this continuous endpoint. Safety information lists one serious adverse event in the spironolactone group and none in the placebo group; death counts are not reported in the registry record.