Ranolazine and Microvascular Angina by PET in the Emergency Department: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ranolazine and Microvascular Angina by PET in the Emergency Department (NCT02052011), a randomized phase 4 study. The primary outcome is Coronary Flow Reserve.

2. Clinical Question

3. Trial Design

RAMP-ED is recorded as a Phase 4 randomized, quadruple-masked, parallel-group trial sponsored by Yale University. The registry lists enrollment of 31. Its recorded start is 2014-04, its primary completion is 2015-11, and its status is completed. These details describe the study record, but do not establish how many participants completed treatment or contributed data to the primary analysis.

The two recorded interventions were ranolazine and placebo. Participants assigned to the intervention group were to take extended-release ranolazine over 4 weeks: 500 mg twice daily during the first week, then 1000 mg twice daily for the remaining period. The record says dosing would be adjusted with concomitant use of diltiazem, verapamil, erythromycin, simvastatin or metformin. Participants in the placebo control group were to take a placebo pill twice daily for 4 weeks.

Random allocation and a parallel model indicate that the planned comparison was between groups assigned to separate treatment regimens. “Quadruple” is the registry’s masking designation; the identities of the masked parties and practical details of how masking was maintained are not reported in the registry record. The method used to generate the random sequence, allocation concealment procedures, and any deviations from assigned treatment are also not reported.

The registry identifies microvascular angina as the condition and describes the study as examining chest pain related to disease of the heart’s small vessels. The eligibility criteria, recruitment procedures, baseline participant characteristics and analysis population are not reported in the registry record. Enrollment and completion dates alone do not show whether recruitment, follow-up or analysis followed the original 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.

Overall Study

Reasons for not completing this 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.

6. Primary Endpoint

The registry lists the primary outcome as Coronary Flow Reserve, measured over 4 weeks.

The primary endpoint is coronary flow reserve, a continuous measure reported as a ratio. The registry describes it as the ratio between myocardial blood flow during stress and at rest, measured using cardiac PET. The intended outcome comparison concerns changes in coronary flow reserve among patients receiving ranolazine versus control at 4 weeks.

In general, a stress-to-rest flow ratio provides a way to describe how myocardial blood flow responds to stress relative to resting flow. It is relevant to a study of microvascular angina because the registry frames that condition as disease of the heart’s small vessels. A physiological measure can address a different question from a symptom measure: it characterizes blood-flow response rather than directly quantifying chest pain or day-to-day functioning. The record does not specify a symptom endpoint as the primary outcome.

The endpoint is described as a mean with standard deviation as the dispersion measure. That choice would summarize the group’s average value and the spread of individual values, if the underlying measurements and analysis were reported. The registry record does not report the numerical coronary flow reserve values, changes, group comparison, confidence interval or test result. Therefore, the planned measure and timeframe can be described, but the observed outcome cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous and is described using a mean and standard deviation. In general, a mean gives the arithmetic average of measurements within a group, while a standard deviation describes how spread out those measurements are around the average. These summaries characterize the data but do not, by themselves, show the uncertainty in a treatment comparison. A group comparison requires a defined contrast between the groups, and its uncertainty is commonly described with a confidence interval.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, although precision alone does not establish clinical importance. For this trial, the registry record does not report a primary effect estimate or confidence interval. It is therefore not possible to assess precision for the coronary flow reserve comparison.

Why does the analysis need a clear comparison?

The primary outcome description specifies change in coronary flow reserve for ranolazine versus control at 4 weeks. To interpret that question, the analysis must define how change is calculated, which measurements contribute, and which groups are compared. The outcome-processing note states that the primary outcome has several categories or time points and was not reduced to one comparison. The record does not identify those categories or time points in enough detail to reconstruct a single contrast. It also does not report the statistical model or the handling of repeated measurements, if any.

What can be said about the planning illustration?

The stated planning assumptions describe an illustration based on the observed effect, not the trial’s own design. The assumptions specify a two-sided significance level of 0.05, equal allocation between arms and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated convention is total events; for other calculations, it is participants per arm. These are planning conventions, not evidence about the trial’s observed statistical power. The record does not report a sample-size justification for the original trial, and planning illustrations should not be mistaken for the trial’s design calculation.

In general, sample-size planning asks how much information a future study might need to detect a chosen effect under specified assumptions. Such calculations depend on assumptions about variability, allocation, significance level and the target effect. When the target is defined as a fraction of an observed effect, the result is conditional on that observed estimate and may be sensitive to its uncertainty. It is not a measure of the probability that the completed trial found an effect. The registry record does not report the numerical observed effect needed to independently assess that planning basis.

Why can variation matter?

Standard deviation describes variation among individual measurements. In general, unusually large variation relative to a group difference makes an estimate less precise. Some statistical outcomes can also show over-dispersion, where variability exceeds what a model assumes; if that occurs, standard errors and uncertainty estimates may be understated unless the analysis accounts for it. That is a general consideration, not a claim that over-dispersion occurred in this trial. The registry record does not report the underlying outcome distribution or a model with which to assess this issue.

Randomization supports a between-group comparison by assigning participants to treatment groups according to a chance process. It does not remove the need to report how the assignment was generated, how outcomes were analyzed, and which participants were included. The record identifies randomized allocation and a parallel model but does not report the randomization procedure, analysis population, adjustment variables, model specification or missing-data method. Those omissions limit independent assessment of the analysis. No recalculated comparison is available from the registry outcome information, so there is no independent numerical estimate to set alongside a sponsor-reported analysis.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis considers several outcomes, time points, groups or comparisons. In general, conducting multiple tests can increase the chance of finding an apparently notable result by chance unless the analysis plan addresses that issue. The registry lists one primary outcome measure and one analysis, but the outcome-processing note says the primary outcome has several categories or time points and was not reduced to one comparison. The record does not explain how these were handled or whether any adjustment for multiple comparisons was planned or used.

The primary outcome is described at 4 weeks, but the record does not supply a numerical result for that endpoint or clarify how the several categories or time points relate to the stated timeframe. It does not report a prespecified hierarchy, a selected contrast, or an adjustment procedure. These analysis details are not reported in the registry record, so the multiplicity implications cannot be evaluated.

Missing data and analysis populations are also important to interpretation. The registry record does not report the number of participants with an available primary outcome, the reasons for any missing measurements, or the method used to handle missing data. It does not specify whether the primary analysis followed assignment regardless of treatment received, included only participants meeting particular criteria, or used another population definition. Enrollment alone cannot answer these questions. Without those details and the underlying outcome results, the completeness and robustness of the primary comparison cannot be assessed.

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 non-serious adverse event terms

The registry reports serious adverse events separately from other adverse events. For serious adverse events, the ranolazine intervention group has 0 affected participants among 21 at risk, and the placebo control group has 0 affected participants among 10 at risk. These are the recorded counts in the registry, not evidence that every possible safety outcome was assessed or that the treatments have equivalent safety.

For other adverse events, the record lists 3 affected participants among 21 at risk in the intervention group and 0 among 10 at risk in the placebo control group. These counts should be read as event reporting within the groups shown, not as a complete account of event type, timing, severity or relationship to treatment. The record does not provide the terms for these other events in the registry record for interpretation.

Deaths are recorded as null for both groups; that is not the same as a reported count of zero. Death information is therefore not reported in the registry record. The registry also does not report event-level details or follow-up completeness. Small group counts and incomplete event descriptions limit what can be inferred from these figures; they do not establish a comparative safety profile.

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

The record gives a clear outline of the question RAMP-ED was designed to address: a randomized comparison of ranolazine and placebo, with coronary flow reserve measured by cardiac PET and a stated timeframe of 4 weeks. It also records the treatment regimens, masking designation, parallel design and enrollment. These details explain the intended study structure, but they are not a report of the primary outcome findings.

The primary result is not reported in the registry record. As a result, the posted information does not establish whether coronary flow reserve changed in either group, whether the groups differed, how large any difference was, or how precise an estimate might be. It also does not establish whether any observed change would correspond to a meaningful difference in symptoms or other patient outcomes. The endpoint is a physiological measure, not a direct report of chest pain relief.

Missing numerical results should not be interpreted as a finding of no effect, nor as evidence that the intervention was beneficial. The registry’s completed status indicates the recorded study status, not the direction or quality of its results. Likewise, the adverse-event counts are descriptive registry entries and cannot, on their own, establish that one regimen is safer than the other.

The registry outcome note further says that the primary endpoint has several categories or time points and was not reduced to one comparison. This leaves the exact primary contrast unclear in the posted information. Without a defined contrast, analyzed population, result estimate and uncertainty measure, readers cannot judge the strength of evidence for the stated primary question. The appropriate interpretation is limited to what the record documents about design and planned measurement; the treatment effect remains unreported.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it places a physiological measure at the center of a randomized, placebo-controlled question about microvascular angina. Coronary flow reserve is defined in the record as a stress-to-rest myocardial blood-flow ratio measured by cardiac PET. That makes the analysis question distinct from one based directly on reported chest pain, even though the trial’s brief summary frames the condition around chest pain from disease of the heart’s small vessels.

The design also illustrates why the presence of randomization and masking does not, by itself, make a result interpretable. A reader still needs a clearly defined outcome contrast, the numerical estimate, uncertainty around that estimate, and information about the participants included in the analysis. Here, the record describes random allocation, quadruple masking and a parallel model, but does not report the primary outcome result or the details needed to assess its analysis.

The outcome-processing note is especially relevant: it indicates several categories or time points without reducing them to one comparison. That issue matters because the question a reader evaluates should match the comparison that was planned and analyzed. If the endpoint can be represented in multiple ways, the selected measure and the handling of multiplicity affect interpretation.

Finally, the safety entries show why counts need context. The serious-event counts are zero in both recorded groups, while other adverse-event counts differ; deaths are not reported as numerical counts. Those entries are informative as registry records but do not replace detailed event descriptions or the primary efficacy result. Together, these features make RAMP-ED a useful example of separating trial design information from the evidence needed to judge a treatment comparison.

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 trial-specific limitation in the registry record is the absence of a numerical result for the primary endpoint. The record identifies coronary flow reserve, its measurement by cardiac PET and the 4-week timeframe, but does not report group values, changes, an effect estimate, a confidence interval or a test result. The primary comparison therefore cannot be evaluated for direction, magnitude or precision.

The outcome-processing note says that several categories or time points were not reduced to one comparison. The record does not explain what those categories or time points are, how the primary contrast was selected, or how they relate to the stated endpoint timeframe. This limits clarity about what the primary analysis represents and how multiple potential comparisons were handled.

Important design and analysis details are also absent. Eligibility criteria, participant characteristics, the randomization procedure, the identity of masked parties, protocol deviations, outcome completeness, analysis population and missing-data approach are not reported in the registry record. These details would help readers assess comparability, potential bias and the applicability of the analysis.

The safety information is limited to counts for serious and other adverse events, with no event descriptions in the record. Deaths are null rather than reported as a numerical count. Finally, the record does not report the original sample-size justification. The planning assumptions describe an illustration based on an observed effect, but without a reported primary effect estimate its basis cannot be evaluated from the registry outcome information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ranolazine and Microvascular Angina by PET in the Emergency Department — NCT02052011.
• Registry record last updated 2017-05-16; status last verified 2017-02.
• Results first posted 2017-05-16.
• 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.

18. Record Summary

NCT02052011, titled “Ranolazine and Microvascular Angina by PET in the Emergency Department,” is recorded as a completed Phase 4 randomized, quadruple-masked, parallel-group study sponsored by Yale University. Enrollment is listed as 31. The recorded start is 2014-04 and primary completion is 2015-11.

The trial compared extended-release ranolazine with placebo over 4 weeks. Its primary outcome was coronary flow reserve measured by cardiac PET, described as a mean with standard deviation and assessed at 4 weeks. The registry record does not report the numerical primary outcome comparison, and notes that several categories or time points were not reduced to one comparison.

Serious adverse-event counts are recorded as 0 in each group; other adverse-event counts are 3 in the intervention group and 0 in the placebo group. Deaths are not reported as numerical counts. These entries do not substitute for the unreported primary result or detailed event information.