Ranolazine and Pulmonary Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ranolazine and Pulmonary Hypertension (NCT01174173), a na phase 3 study. The primary outcome is Improve Angina Symptoms.

2. Clinical Question

The study asked whether ranolazine treatment was associated with improvement in angina symptoms among patients with pulmonary arterial hypertension and angina attributed to right ventricular ischemia. The registry record describes testing participants’ heart function, exercise capacity, chest pain and quality of life after 3 months of treatment. The primary outcome was average improvement in WHO Functional Class from baseline to 3 months.

This is a question about change during treatment, not a randomized estimate of the difference between ranolazine and another treatment or no treatment. Without a concurrent control group, a change from baseline cannot by itself distinguish a treatment effect from other explanations, such as natural fluctuation or changes over time. The registry record’s description establishes the intended outcome and assessment period, but does not provide the primary outcome estimate or its uncertainty.

3. Trial Design

The registry record identifies this as a completed phase 3 study with a single-group model, no masking and allocation recorded as NA. It lists Northwestern University as the sponsor. The study began in 2010-06, and primary completion was recorded as 2014-01. Enrollment was 11.

Participants received ranolazine, recorded at 1000 mg PO BID. The primary assessment compared WHO Functional Class at baseline with the assessment at 3 months. The primary analysis population is described as participants who completed the study, with average change in WHO Functional Class calculated from baseline to 3 months. The number who completed and were included in that analysis is not reported in the registry record.

The registry record’s study summary describes additional assessments of heart function, exercise capacity, chest pain and quality of life. Listed secondary outcomes are right ventricular perfusion on cardiac MRI, absolute right ventricular longitudinal strain and right ventricular hemodynamics. The record lists 6 outcome measures and 5 analyses. Details of the remaining measures and the relationship between the outcome-measure and analysis counts are not reported in the registry record.

A single-group before-and-after design can describe how measurements changed among the participants assessed. It does not provide a parallel untreated or active-control group for estimating what would have happened over the same period without ranolazine. The absence of masking also means that participants and study personnel were not masked, as recorded in the registry. How this was handled in outcome assessment is not reported in the registry record.

Although the study is classified as phase 3, that label does not change the design features recorded in the registry: one group, no masking and no randomized comparison. The statistical interpretation therefore depends on within-participant change and the completeness and precision of the measurements, rather than on a between-group treatment contrast. A detailed protocol, recruitment flow and reasons for any non-completion are not reported in the registry record.

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: Analysis was performed on all participants who completed as average change in WHO Functional class score from baseline to 3 months (Baseline, 3 months)

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: We prospectively enrolled 11 patients with WHO Group 1 PAH with mean age was 48±13 years and 73% of patients were women. Nearly half of the study participants were non-white.

6. Primary Endpoint

The registry lists the primary outcome as Improve Angina Symptoms, measured over 3 months.

The primary endpoint was average improvement in WHO Functional Class, assessed as change from baseline to 3 months. The scale runs from 1 to 4, and higher scores indicate more impairment. In general, a functional-class measure is intended to represent a patient’s level of functional limitation; tracking it over time can capture a change in reported or assessed status that may not be represented by a laboratory measure alone.

The registry record describes the endpoint as a mean of a continuous measure and gives standard deviation as the dispersion measure. The underlying scale has only four ordered categories, however, so its values are categorical rankings rather than measurements with intrinsically equal intervals. Reporting an average change treats differences between adjacent categories in a way that supports a numerical summary. That can be useful for describing the group’s average direction and magnitude of change, but it does not show whether individual participants changed in the same way. A group mean can also conceal variation in responses.

The outcome description calls the measure “average improvement,” while the scale description says higher scores reflect more impairment. Read together, improvement would correspond to movement toward a less impaired classification, but the registry record does not state the numerical direction convention used for the reported change. The actual mean change, standard deviation, number analyzed and any confidence interval are not reported in the registry record. Thus, the endpoint’s definition is available, but the observed estimate and its precision cannot be evaluated from the registry information stated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is described as a mean change in a continuous measure, with standard deviation used to describe dispersion. In general, a mean summarizes the central value of a set of measurements, while a standard deviation describes how spread out those measurements are around the mean. Neither statistic is reported numerically for this endpoint in the registry record. Their stated roles describe the intended summary, not an available estimate.

What does a change score represent?

In general, a change score is calculated by comparing a participant’s measurement at follow-up with that participant’s baseline measurement. The group mean of those changes describes average movement over the observation period. This approach uses the within-participant pairing of measurements. It does not create a control group: everyone in the recorded study group received ranolazine, so the change cannot be directly contrasted with a simultaneous group receiving another condition.

The registry record says the primary analysis used participants who completed the study and describes the outcome as average change from baseline to 3 months. It does not state the exact calculation convention for change, such as which measurement was subtracted from which. The scale’s higher values indicate more impairment, so the sign convention matters when reading a numerical change. That convention and the numerical result are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval expresses a range of values compatible with the data and a specified statistical procedure. A narrower interval indicates greater precision than a wider interval, while an interval that spans values representing different interpretations may leave the direction or practical importance uncertain. A p-value addresses compatibility with a specified null hypothesis under assumptions; it is not a measure of effect size or clinical importance. The registry record does not report a confidence interval or p-value for the primary outcome, so neither precision nor statistical evidence against a null hypothesis can be assessed.

With a small enrollment, estimates can be particularly sensitive to the observations included, although the primary analysis count is not reported. The enrollment figure does not establish how many participants had complete outcome data. Without the estimate, dispersion and analysis count, no numerical assessment of uncertainty is possible. It would be inappropriate to infer precision from the study’s phase or completion status.

What does the scale imply for analysis?

In general, a scale with ordered categories has a rank structure: one category indicates more impairment than another, but equal spacing between categories is not guaranteed by the labels alone. Summarizing changes with a mean can be convenient and can describe average movement, but interpretation depends on treating the category steps as sufficiently comparable for that purpose. The record specifies a mean and standard deviation, but does not report additional analyses of the category distribution, individual transitions, or alternative models. Whether such analyses were conducted is not reported in the registry record.

Variation between participants matters as well as the mean. Some participants could improve, some remain unchanged and others worsen, while the average captures only a single summary of those patterns. A standard deviation can describe spread in the change scores, but it does not reveal the full distribution or the number of participants in each pattern. Those details are not reported in the registry record.

Why does the design affect statistical interpretation?

In general, a randomized concurrent comparison can help distinguish treatment-related differences from changes that would occur over time regardless of treatment, because the groups are compared under the same study period. This study is recorded as single-group, with allocation NA and no masking. Thus, its primary contrast is baseline versus follow-up within the treated group, not ranolazine versus a control. Statistical significance in a within-group change, if reported, would not by itself resolve the lack of a control comparison or establish the cause of the change.

The registry record includes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are assumptions for a planning illustration, not evidence that the trial used a two-arm design. The actual study is recorded as single-group. The numerical planning results and the observed effect are not reported in the registry record, and such planning figures are not observed power.

The protocol’s statistical analysis plan, assumptions for the primary analysis, handling of deviations from assumptions and any interim analyses are not reported in the registry record. These omissions limit assessment of whether the analysis followed a prespecified plan. The endpoint definition and broad summary approach are recorded, but the details needed to reproduce or fully evaluate the analysis are not available.

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("Ranolazine")
n   <- c(8)
m   <- c(1.75)
sp  <- c(0.46)
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  Ranolazine  8  1.750  0.460  1.365  2.135

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 5 analyses. It identifies WHO Functional Class change as the primary outcome and lists secondary outcomes involving right ventricular perfusion on cardiac MRI, absolute right ventricular longitudinal strain and right ventricular hemodynamics. The record does not explain the mapping between the outcome-measure count and analysis count, nor does it report results for the secondary outcomes.

When several outcomes or analyses are examined, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can address that issue by adjusting interpretation or testing thresholds, or by specifying a hierarchy of outcomes in advance. Whether any such approach was planned or used is not reported in the registry record. The number of analyses alone does not establish that a particular adjustment was required or performed.

The primary analysis population is described as all participants who completed, with change assessed from baseline to 3 months. The enrollment is recorded as 11, but the number of completers and the number with primary outcome data are not reported in the registry record. The record does not describe missing-data reasons, imputation, sensitivity analyses, or how incomplete follow-up measurements were handled. It is therefore not possible to assess whether missingness could have affected the estimate or whether the complete-case analysis represents all enrolled participants.

Protocol details on analysis populations, prespecification and missing-data methods are not reported in the registry record. These are material uncertainties when interpreting any outcome estimate, particularly in a single-group study whose primary analysis is restricted to completers.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: inpatient hospitalization (9.1%).

The registry record lists one participant affected by a serious adverse event among 11 participants at risk. It lists 6 participants affected by other adverse events among 11 at risk. Inpatient hospitalization is the top serious adverse-event term, recorded as 9.1%. The record does not provide further event-level descriptions or explain whether the listed term represents all serious events or a particular event category.

These figures describe reports within the ranolazine group. With no control group, they do not estimate how event frequency compares with another treatment or with no treatment. The counts also do not establish that ranolazine caused an event. The registry record does not report the definition or observation window used for these adverse-event summaries, nor does it report deaths; deaths are not reported in the registry record.

Participant counts and event counts are not necessarily interchangeable: one participant may experience more than one event. The record labels participants affected, but does not provide enough detail to reconstruct event totals or timing. The serious and other adverse-event summaries should therefore be read as descriptive safety reporting for this study group, not as a comparative estimate of risk.

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

The registry record establishes that a completed single-group study assessed ranolazine in patients described as having angina due to right ventricular ischemia in pulmonary arterial hypertension. It specifies a primary endpoint: average improvement in WHO Functional Class from baseline to 3 months among participants who completed the study. The scale runs from 1 to 4, with higher scores indicating more impairment.

The central limitation for interpreting the result is that the numerical primary outcome is not reported in the registry record. There is no mean change, standard deviation, confidence interval or p-value stated. The record therefore does not allow readers to determine whether the average score moved toward less impairment, how large any change was, or how precisely it was estimated. The study’s completed status does not fill this gap.

Even if a before-and-after estimate were available, this design would describe change over time in one treated group. Without a concurrent control group, it would not isolate the effect of ranolazine from natural fluctuation, time trends, other care or measurement influences. Because the study was unmasked, expectations or assessment practices are also potential considerations; the registry does not report enough detail to evaluate them.

The same caution applies to the safety summaries. The listed counts describe adverse events reported among participants in the ranolazine group, not a comparison of risks. They cannot by themselves establish causality or show how the event frequency differs from another treatment condition.

Accordingly, the registry information supports a description of the clinical question, design, endpoint and some adverse-event counts. It does not support a conclusion that ranolazine did or did not improve symptoms, nor a comparative claim about efficacy or safety. The endpoint results, their uncertainty, detailed missing-data handling and comparative evidence are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it pairs a clinically oriented before-and-after question with a design that has no concurrent comparator. Repeated measurement can describe how an outcome changes within participants, but a change over time is not equivalent to a treatment contrast. That distinction is essential when readers interpret any single-group clinical study.

The primary measure also raises a useful issue about summaries. WHO Functional Class is described as a scale from 1 to 4, with higher scores indicating more impairment, while the analysis is described as a mean change with standard deviation. Such a summary can be compact and interpretable as average movement, but it does not display the pattern of individual category changes. A mean alone cannot show whether the group’s average reflects broadly similar shifts or a mixture of different experiences.

Transparency about precision is equally important. The registry record defines the endpoint and analysis population in broad terms, but does not report the estimate, variability, confidence interval or p-value. Without those statistics, a reader cannot evaluate the size or precision of the measured change. Reporting that a study is complete is not a substitute for reporting its results.

The record also illustrates why outcome and missing-data plans matter. It lists multiple outcome measures and analyses, while multiplicity procedures and the handling of incomplete measurements are not reported. Those details help readers understand how results were selected and how well an analysis may represent participants who enrolled.

These points apply broadly to clinical research: design, outcome definition, analysis population, uncertainty and reporting completeness all shape what a result can support. In this record, the design and endpoint are described, but the primary numerical result and several analysis details are not reported. That limits statistical interpretation independently of the study’s phase or completion status.

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.

The most direct limitation is the absence of the primary outcome values in the registry record. The mean change, standard deviation, confidence interval and p-value are not reported, so the direction, magnitude and precision of the endpoint cannot be assessed. The number of participants included in the primary analysis is also not reported; the record describes analysis among completers but does not state how many completed.

The single-group design has no concurrent control condition, and allocation is recorded as NA. It can describe baseline-to-follow-up change in the treated group, but it cannot separate treatment effects from other influences over time. The study is also recorded as unmasked. Whether outcome assessors were independent or whether assessment procedures reduced bias is not reported in the registry record.

The primary outcome is a mean change on a four-category scale. The scale is ordered and higher categories indicate more impairment, but equal spacing between categories is not established by the description. The record does not provide the distribution of individual category changes, the exact sign convention for change or alternative analyses.

Further limitations include absent details on the protocol, eligibility criteria, missing-data handling, multiplicity procedures, analysis assumptions and interim analyses. Secondary outcome results are not reported in the registry record. The safety record gives summary counts and a serious-event term, but does not state the observation window, event-level detail or comparative data. Together, these gaps constrain both quantitative interpretation and assessment of how robust the findings would be to alternative analytic choices.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ranolazine and Pulmonary Hypertension — NCT01174173.
• Registry record last updated 2018-05-11; status last verified 2018-04.
• Results first posted 2015-04-23.
• 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

The registry record identifies NCT01174173, “Ranolazine and Pulmonary Hypertension,” as a completed phase 3, single-group study sponsored by Northwestern University. It records no masking, allocation as NA and enrollment of 11. The study began in 2010-06, with primary completion in 2014-01.

The intervention was ranolazine at 1000 mg PO BID. The primary endpoint was average improvement in WHO Functional Class from baseline to 3 months among participants who completed the study. The scale ranges from 1 to 4, with higher scores indicating more impairment. Secondary outcomes included right ventricular perfusion on cardiac MRI, absolute right ventricular longitudinal strain and right ventricular hemodynamics.

The registry record does not report the numerical primary outcome result, its uncertainty, the number included in the completed-participant analysis, or detailed missing-data and multiplicity methods. It lists one participant affected by a serious adverse event and 6 affected by other adverse events, with inpatient hospitalization recorded as the top serious term at 9.1%. These safety figures are descriptive and have no control-group comparison.