Beta-blockers in Pulmonary Arterial Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Beta-blockers in Pulmonary Arterial Hypertension (NCT02507011), a randomized phase 2 study. The primary outcome is Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI.

2. Clinical Question

The trial record identifies the study as randomized, double-blind, placebo-controlled, and crossover. Its stated focus is carvedilol for right ventricular dysfunction in pulmonary arterial hypertension. The primary endpoint is a change in right ventricular ejection fraction, rather than a clinical event or symptom score. This makes the question one of whether the recorded heart-imaging measure changed during treatment periods; the posted summaries alone do not establish how participants’ measurements differed between periods or how treatment sequence was handled.

The planned population in the brief summary is more specific than the small enrollment listed in the registry: it describes pulmonary arterial hypertension, functional class II or III symptoms, and right ventricular ejection fraction below 45%. The record lists 2 participants enrolled. It does not explain the relationship between that enrollment and the planned 26 participants, nor does it describe why the study was terminated.

3. Trial Design

NCT02507011 is listed as a randomized phase 2 study sponsored by the University of Minnesota. The registry identifies double masking and a crossover model, with carvedilol and placebo as the interventions. The sequence descriptions specify carvedilol followed by placebo for one sequence and placebo followed by carvedilol for the other. The record does not report the method used to generate or conceal the random allocation.

The study is marked terminated. Its listed start date is 2016-01-31, and its primary completion date is 2019-07-01. The brief summary describes a planned study of 26 patients treated for 6 months, while the registry enrollment field lists 2. The record does not explain the difference between the planned enrollment and the listed enrollment, or report how many participants completed each treatment period.

A crossover design differs from a parallel-group design because participants can receive both treatments in sequence. In general, comparisons in such a design can make use of measurements from the same participant under each treatment, which may account for stable differences between people. Interpretation depends on how measurements are assigned to periods and sequences and whether the analysis addresses period effects or carryover from an earlier treatment. The registry record does not report those details, a washout procedure, or a crossover-specific analysis.

The primary outcome is a continuous measure: mean change in right ventricular ejection fraction as measured by cardiac MRI, with a 6-month timeframe. The posted arm summaries list 2 participants in each treatment arm. Because this is a crossover study, the arm counts should not be read as proof that there were 4 distinct participants. The registry does not provide participant-level data or a sequence-by-period account that would clarify the overlap.

The record contains no posted analyses and marks the continuous two-arm comparison as missing or not estimable. It does not report a statistical analysis plan, sample-size justification, interim analyses, or details explaining termination. Those omissions limit what can be inferred about the intended analysis and the reasons the trial stopped.

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.

First Intervention

Second Intervention

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 Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI, measured over 6 months.

The primary endpoint is mean change in right ventricular ejection fraction measured by cardiac MRI, with a 6-month timeframe. Ejection fraction is generally understood as the proportion of blood in a ventricle that is ejected with each contraction. A change in this measure describes movement in a cardiac imaging measure over time; it is not itself a direct measure of symptoms, quality of life, or a clinical event.

Cardiac MRI is the measurement method named in the registry. In general, imaging-based measures can give a quantitative description of heart structure or function, allowing researchers to compare measurements taken at different times or under different treatment conditions. The registry does not report the MRI acquisition protocol, how images were read, whether readers were blinded to treatment, or how the change was calculated for each participant.

The posted result describes the endpoint as a mean and gives a standard deviation for each arm. The carvedilol arm has a mean of 10.0 percent and standard deviation of 4.0; the placebo arm has a mean of 2.5 percent and standard deviation of 2.0. These summaries describe the posted arm-level results. They do not provide a treatment-effect estimate with uncertainty, and the registry does not post an analysis comparing the treatments. The endpoint’s clinical interpretation is therefore constrained by the limited summary and the absence of the comparison analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a continuous endpoint is summarized with a measure of location and a measure of spread. Here, the registry reports a mean and standard deviation for each treatment arm. The mean is the average of the observations used for that summary; the standard deviation describes how far observations tend to vary around that average. These quantities are useful descriptions, but they do not by themselves quantify uncertainty about a treatment contrast.

What does a treatment comparison estimate?

In general, a treatment-effect estimate is a defined contrast between outcomes under the intervention and comparator. Depending on the design and analysis, a contrast could be based on group means or on within-participant differences. Its interpretation depends on the endpoint definition, analysis population, treatment assignment, and handling of repeated measurements. The registry provides arm means, but no contrast estimate, confidence interval, or p-value. It also flags the continuous two-arm comparison as missing or not estimable. A treatment comparison should therefore not be reconstructed from the arm summaries as if it were the sponsor’s analysis.

Why does crossover matter?

In general, crossover trials expose participants to treatments in sequence, so observations may be related within the same participant. A paired analysis can account for stable participant characteristics shared across periods. It also needs to consider whether outcomes differ by period, whether treatment order matters, and whether the effect of an earlier treatment persists into a later period. Those are general design and analysis considerations, not reported findings about this trial. The registry lists the treatment sequences but does not report period-level data, paired results, a washout procedure, or an analysis addressing these issues.

The arm summaries list 2 participants for carvedilol and 2 for placebo. In a crossover study, the same participants may contribute observations under both treatments, so those arm counts should not automatically be added to infer the number of distinct participants. The registry separately lists enrollment of 2, but does not provide participant-level information to connect the enrollment field to the outcome summaries or describe completion by sequence.

How should uncertainty be assessed?

A confidence interval is, in general, a range of values compatible with the data under a specified statistical model and procedure. It communicates the uncertainty around an estimate; it does not guarantee that the true value lies in the interval. The registry does not report a confidence interval for the treatment comparison. A p-value, when reported, describes how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the analysis assumptions. It is not a measure of the size or clinical importance of an effect. No p-value is reported for this comparison.

The posted standard deviations are not substitutes for these inferential quantities. They describe variability among observations within each arm, while a confidence interval for a treatment contrast would also depend on the analysis structure and available data. In a crossover trial, the association between the two measurements from each participant can be relevant to the uncertainty of a paired contrast. That association is not reported, so the precision of a paired comparison cannot be recovered from the arm summaries.

What can sample-size illustrations tell readers?

In general, a sample-size calculation depends on assumptions about the effect to detect, variability, allocation, significance level, and desired power. A planning illustration based on an observed effect is not observed power: it describes a hypothetical design under specified assumptions, not the probability that the completed trial has established a result. The registry gives planning assumptions involving a two-sided significance level of 0.05, equal allocation, a normal approximation, and a target effect expressed as a fraction of the observed effect. It does not give calculated participant-per-arm values in the record summarized for this trial. The record also does not report the trial’s own sample-size justification.

The planned enrollment of 26 in the brief summary and listed enrollment of 2 are distinct pieces of registry information. The record does not explain the difference, and neither figure supplies a basis for an unreported power calculation. With no posted comparison analysis, no confidence interval, and very limited arm-level summaries, statistical precision cannot be established from the outcome means and standard deviations alone.

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("Carvedilol", "Placebo")
n   <- c(2, 2)
m   <- c(10, 2.5)
sp  <- c(4, 2)
sd  <- sp      # posted standard deviations
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  Carvedilol  2  10.000  4.000  -25.939  45.939
CARM  Placebo  2  2.500  2.000  -15.469  20.469

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted secondary outcomes. It reports no analyses. This leaves no multiplicity procedure or hierarchy of hypotheses to evaluate. In general, multiplicity arises when several outcomes, timepoints, treatment contrasts, or subgroup analyses are tested; the chance of at least one false-positive result can increase when many tests are considered. A prespecified strategy may address this, but the registry does not report a statistical analysis plan or any multiplicity adjustment.

Missing-data handling is also not reported in the registry record. It does not state how missing MRI measurements, incomplete treatment periods, or withdrawals were handled, nor does it identify an analysis population such as all randomized participants or participants with complete data. The record does not report the number of participants with endpoint measurements at each period or explain whether the posted summaries include everyone enrolled.

These omissions matter especially in a crossover design, where missing measurements in either treatment period can affect a participant’s contribution to a paired comparison. In general, complete-case analyses and methods that use available observations rely on different assumptions about why values are missing. Without the participant flow, missingness details, and analysis methods, readers cannot assess those assumptions or determine whether the posted summaries represent all randomized participants.

The registry marks the study terminated and lists enrollment of 2, while the brief summary describes planned enrollment of 26. The record does not report why recruitment stopped or whether termination affected missingness, outcome availability, or the analysis population. No explanation should be inferred from the status alone.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hf exaceberation/electrolyte imbalance (50.0%).

The serious adverse event summaries list 2 participants at risk in each arm and 1 participant with a serious adverse event in each arm. The registry lists no deaths in either arm. These are counts from a very small set of participants; they should be read as descriptive observations, not as precise estimates of comparative safety.

The record also lists other adverse events for 1 participant in the carvedilol arm and 2 participants in the placebo arm, with 2 participants at risk in each arm. Those entries are separate from the serious adverse event counts. The registry identifies “HF Exaceberation/Electrolyte Imbalance” as a top serious term and gives 50.0%. It does not provide enough detail in the posted summary to determine the event-level accounting behind that term or its relationship to the participant counts.

In general, adverse-event counts do not establish that a treatment caused an event. Causal interpretation depends on clinical review, timing, definitions, exposure, and the comparison design. The registry record does not report the detailed event narratives or timing needed for such an assessment. With the small numbers listed, these summaries are not a stable basis for comparing risks between treatments.

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

The posted results establish that the registry contains arm-level summaries for the primary continuous outcome and adverse events. For right ventricular ejection fraction change measured by cardiac MRI, the carvedilol arm mean is 10.0 percent with standard deviation 4.0, and the placebo arm mean is 2.5 percent with standard deviation 2.0. The record lists 2 participants in each arm. It also lists 1 participant with a serious adverse event in each arm and no deaths.

Those observations do not establish the size or precision of a treatment effect. There is no reported contrast estimate, confidence interval, or p-value, and the registry marks the continuous comparison as missing or not estimable. Because the design is crossover, arm-level means do not show the paired participant-level changes or account for treatment sequence and period. The posted summaries therefore cannot answer whether the treatments differed under an appropriate crossover analysis.

The results also do not establish how representative the participants were of the population described in the brief summary. That summary describes planned enrollment of 26 patients with specified symptoms and an ejection fraction threshold, while the enrollment field lists 2. The registry does not explain the discrepancy or report the characteristics of the enrolled participants in detail.

In general, statistical evidence and clinical meaning are related but distinct. A measured change in an imaging endpoint is not automatically evidence of a change in symptoms or other outcomes. The registry does not report secondary outcomes, detailed clinical events, or a complete analysis that would support broader conclusions. The findings should be read as limited descriptive results from a terminated trial, not as a definitive estimate of comparative efficacy or safety.

14. Why This Trial Matters Statistically

This record is statistically informative in part because it makes the gap between a planned trial and the posted results visible. The brief summary describes a randomized crossover study intended to enroll 26 patients, while the enrollment field lists 2. The registry marks the study terminated and posts outcome summaries for 2 participants in each treatment arm. It does not explain the difference between the planned and listed enrollment or why the trial ended.

The record also illustrates why design details matter when interpreting summary statistics. In a crossover study, participants can receive both treatments, and the within-participant comparison may be central to the analysis. Arm-level means and standard deviations do not reveal that paired comparison. Without period-specific or participant-level results, the posted summaries cannot show how sequence and period were handled.

A further statistical point is the distinction between descriptive results and inferential results. The registry reports means and standard deviations, but no treatment-comparison analysis, confidence interval, or p-value. Readers can describe what the arm summaries say, but cannot assess the estimated contrast’s precision or statistical compatibility with different possible effects from the registry record.

Finally, the case emphasizes that sample-size planning and observed results answer different questions. A planning illustration based on an observed effect is hypothetical and does not measure achieved power. The record does not report the trial’s own sample-size justification or calculated planning values. The combination of a terminated status, very small listed enrollment, and absent analysis highlights the importance of transparent reporting of participant flow, missing data, and design-specific analyses.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information reported for this trial. The registry lists enrollment of 2, whereas the brief summary describes a planned enrollment of 26. It does not explain why these figures differ. The study is marked terminated, but the reason for termination is not reported in the registry record. It is also unclear from the record whether all planned treatment periods and endpoint assessments were completed.

The primary endpoint summaries are arm-level only. Although the study is described as a crossover, the record does not provide sequence-specific or period-specific values, paired participant-level data, or a treatment-comparison estimate. It does not report how a crossover analysis would account for period effects, treatment order, or carryover. A washout procedure is not reported.

The record does not identify the analysis population, the number of participants contributing endpoint data by period, or how missing measurements were handled. It does not report baseline characteristics that would help readers understand the enrolled participants or assess how closely they matched the population described in the brief summary. The MRI measurement and reading procedures are not detailed.

The registry posts no analyses and marks the continuous two-arm comparison as missing or not estimable. No confidence interval, p-value, statistical analysis plan, interim analysis information, or trial-specific sample-size justification is reported. Adverse event summaries are sparse and do not include detailed timing or event narratives. These limitations mean that the posted data support only a narrow descriptive account; they do not allow a well-characterized estimate of comparative treatment effects or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Beta-blockers in Pulmonary Arterial Hypertension — NCT02507011.
• Registry record last updated 2020-06-16; status last verified 2020-05.
• Results first posted 2020-06-16.
• 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.

19. Record Summary

NCT02507011 is a randomized, double-blind, phase 2, placebo-controlled crossover study sponsored by the University of Minnesota and marked terminated. The registry lists a start date of 2016-01-31, primary completion date of 2019-07-01, and enrollment of 2. The brief summary describes planned enrollment of 26 patients with pulmonary arterial hypertension, functional class II or III symptoms, and right ventricular ejection fraction below 45%.

The primary outcome is mean change in right ventricular ejection fraction by cardiac MRI at 6 months. Posted arm summaries list 2 participants per arm, with mean change of 10.0 percent and standard deviation 4.0 for carvedilol, and mean change of 2.5 percent and standard deviation 2.0 for placebo. No treatment-comparison analysis is posted; the record marks that comparison missing or not estimable. The registry does not report why the study was terminated, how missing data were handled, or the analysis plan.