Targeting Right Ventricle in Pulmonary Hypertension Gilead: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeting Right Ventricle in Pulmonary Hypertension Gilead (NCT02829034), a randomized phase 4 study. The primary outcome is Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage).

2. Clinical Question

The trial was designed to assess ranolazine in participants with pulmonary hypertension and right ventricular dysfunction who were receiving stable pulmonary hypertension therapies. Its primary endpoint focuses on change in right ventricular ejection fraction, rather than a clinical event or a measure of symptoms. The registry record also names percent change in 6min-walk-test distance and change in N-terminal Pro B-type Natriuretic Peptide as secondary outcomes.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group, placebo-controlled, multicenter study listed as Phase 4. The registry record identifies the University of Pennsylvania as sponsor and reports enrollment of 22. The study status is completed. The recorded start was 2016-07 and primary completion was 2017-12.

Participants were assigned to ranolazine or placebo. The ranolazine schedule began at 500mg by mouth twice per day and increased after two weeks to 1000mg by mouth twice per day; placebo was taken by mouth twice per day. The record describes participants as having pulmonary hypertension, right ventricular dysfunction with RVEF below 45%, and stable pulmonary hypertension therapies.

Masking is listed as quadruple, but the registry record does not identify which roles were masked or describe how masking was maintained. The allocation method beyond randomization, the randomization sequence, and any allocation-concealment procedures are not reported in the registry record. The record does not report the planned sample-size justification or details of the intended statistical plan.

The primary outcome is described for participants who completed follow-up at 6 months, while its stated timeframe is 26 weeks. The arm-level outcome summaries include 9 participants in the ranolazine group and 6 in the placebo group. The safety summaries use different group counts, as described in the safety reading. Reasons for these differences and details of participant flow 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

Analysis population for the primary outcome, as defined in the registry: participants who completed follow up study at 6 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.

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage), measured over 26 weeks.

The primary endpoint is absolute change from baseline in right ventricular ejection fraction, measured by MRI and expressed as a percentage. Right ventricular ejection fraction describes the proportion of blood in the right ventricle that is ejected with each contraction. In general, it is used as a measure of right ventricular pumping function, which is relevant to a study focused on pulmonary hypertension and right ventricular dysfunction.

The outcome timeframe is 26 weeks. The registry describes the primary outcome population as participants who completed follow-up at 6 months. It reports least-squares mean estimates and standard errors for each treatment group. The ranolazine estimate is 7.56 with a standard error of 1.72; the placebo estimate is -3.99 with a standard error of 2.23. These are separate arm-level summaries, not a reported between-group treatment effect.

In general, a baseline-change endpoint focuses on how a measure shifts over follow-up, while MRI provides an imaging-based assessment of ventricular function. The registry record does not report a confidence interval or an inferential test for the between-group difference. It also does not give details of the MRI reading or analysis procedures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports least-squares means and standard errors for the primary continuous outcome. The summaries are based on change in right ventricular ejection fraction from baseline, measured by MRI, with a stated timeframe of 26 weeks. The outcome is expressed as a percentage. The reported estimates are 7.56 for ranolazine and -3.99 for placebo, with standard errors of 1.72 and 2.23, respectively.

What does a least-squares mean describe?

In general, a least-squares mean is an estimated mean from a statistical model. Depending on the model, it can represent a mean adjusted for variables included in that model. The registry record does not report the model specification, covariates, or other details needed to determine how these estimates were obtained. The label alone does not establish which adjustments were made.

How should the standard errors be read?

In general, a standard error describes the sampling uncertainty of an estimated mean under the analysis assumptions. A smaller standard error indicates a more precise estimate, all else equal. It is not a standard deviation and does not describe the variability among individual participant measurements. The standard errors apply to the separate arm-level estimates. They are not a standard error for the difference between groups.

A confidence interval is a range of values generated by an inferential procedure to communicate uncertainty around an estimate. In general, a confidence interval for the between-group effect would show the range of contrasts reasonably compatible with the data and analysis assumptions. No confidence interval for the treatment-group contrast is reported in the registry record. The record also does not report a p-value or another test result for that comparison.

Why is the between-group estimate important?

In a randomized trial, the central comparative question concerns the outcome under assignment to one group versus the other. Separate arm-level estimates can describe each group, but they do not directly report the estimated contrast or its uncertainty. The registry record indicates that values were missing or not estimable for a two-arm comparison of the continuous endpoint. As a result, the posted arm summaries should not be converted into a claimed treatment effect or a significance conclusion.

In general, comparison methods for continuous outcomes may account for baseline measurements, follow-up values, or other prespecified factors. The appropriate method depends on the trial’s analysis plan and data structure. The statistical model, estimand, and handling of repeated measurements are not reported in the registry record. It is therefore not possible to assess whether the displayed arm summaries reflect a prespecified adjusted analysis or another approach.

What do the planning assumptions mean?

The record describes sample-size calculations as planning illustrations computed from the observed effect, not as the trial’s original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations concern hypothetical future planning under assumptions. They are not observed power and do not establish the probability that this completed trial detected an effect. The registry record does not report the trial’s own sample-size justification.

In general, planning calculations based on an observed effect are sensitive to uncertainty in that estimate. If the observed effect is imprecise, calculations built from it may also be unstable. The planning assumptions do not replace a reported comparative estimate and confidence interval from the trial. The registry record does not report further details about the calculation method or an original target enrollment rationale.

What remains unclear about the analysis?

The registry record does not report the analysis population definition beyond the description of participants who completed follow-up at 6 months. It does not report whether analysis followed randomized assignment, how missing outcome data were handled, whether baseline adjustment was used, or what assumptions were applied to the statistical model. It also does not report an analysis of the named secondary outcomes. These omissions limit assessment of the analysis’s reproducibility and of the uncertainty around the comparative effect.

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", "Placebo")
n   <- c(9, 6)
m   <- c(7.56, -3.99)
sp  <- c(1.72, 2.23)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  9  7.560  5.160  3.594  11.526
CARM  Placebo  6  -3.990  5.462  -9.722  1.742

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary outcome and two secondary outcomes. It does not report whether the analysis plan adjusted for testing multiple outcomes, defined a testing hierarchy, or specified how results would be interpreted across these measures. The registry record does not report analyses for the secondary outcomes. Without those details, the role of multiplicity in interpreting the outcome set cannot be assessed.

The primary endpoint population is described as participants who completed follow-up at 6 months. The primary outcome summaries include 9 participants in the ranolazine group and 6 in the placebo group, while enrollment is reported as 22. The record does not explain the differences in these counts, identify reasons for missing follow-up, or describe whether the analysis used all randomized participants or only those with observed endpoint data.

In general, missing outcome data can affect both precision and the validity of a comparison, particularly if missingness is related to outcomes or differs between groups. Statistical methods can make assumptions about missing data, but those assumptions and any imputation or sensitivity analyses are not reported in the registry record. The record also does not report a detailed participant-flow account or define the analysis population beyond the completion description. These gaps prevent a full appraisal of how incomplete outcome information may have influenced the estimates.

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: heart failure (25.0%).

The registry reports serious adverse event summaries for the ranolazine and placebo groups. The ranolazine group lists 14 participants at risk and 3 affected; the placebo group lists 8 at risk and 2 affected. Deaths are listed as 0 for ranolazine and 1 for placebo. These are safety counts and should not be confused with the smaller group counts reported for the primary outcome.

The record identifies heart failure as a top serious adverse event term, with 25.0% reported. It does not state in this summary how that percentage was calculated or provide further detail about the event cases. The registry also reports other adverse events affecting 11 participants in the ranolazine group and 4 in the placebo group, using group counts at risk of 14 and 8, respectively.

In general, adverse-event counts describe events recorded during a study and do not, on their own, establish that a treatment caused an event. Interpretation depends on event definitions, timing, severity, exposure, and how events were collected. Those details are not fully reported in the registry record. The differences in group counts and the small numbers also warrant caution; the summaries do not provide a precise estimate of comparative safety.

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

The primary outcome summaries show a positive estimated change in right ventricular ejection fraction in the ranolazine group and a negative estimated change in the placebo group. The estimates are 7.56 and -3.99, with standard errors of 1.72 and 2.23. They provide a description of the recorded arm-level outcomes among the primary analysis participants.

They do not provide a reported between-group estimate, confidence interval, or p-value. Without a comparative estimate and its uncertainty, these summaries do not establish the size or precision of a treatment effect. The registry record says values were missing or not estimable for a two-arm comparison of the continuous endpoint. The arm summaries should therefore not be treated as a statistically tested result or as proof of a difference between assigned groups.

The primary outcome is an MRI measure of right ventricular function. It is not itself a direct measure of symptoms, daily activity, hospitalization, or survival. Although the registry names the 6min-walk-test and NT-proBNP as secondary outcomes, it does not report analyses for them. The posted primary summaries therefore do not answer what the trial found for those outcomes.

The participant counts also constrain interpretation. The primary summaries include 9 participants in the ranolazine group and 6 in the placebo group, and the registry does not explain participant flow or missing measurements. The safety summaries use different counts. The record does not report enough information to determine how these features affect the reliability or generalizability of the outcome estimates.

In general, a randomized design helps structure a comparison, but interpretation still depends on the analyzed population, outcome completeness, statistical method, and uncertainty around the contrast. Those details are not fully reported in the registry record. The findings should be understood as posted summaries from this completed study, not as a standalone basis for clinical decisions.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between reporting outcomes by group and reporting the effect of a randomized comparison. The registry gives least-squares mean changes and standard errors for each arm, but it does not report a comparative estimate or inferential test for the primary continuous endpoint. The arm-level direction of change is visible in the reported values, but a treatment contrast and its precision are not available from the registry record.

The difference between the primary-outcome counts and the enrollment count is also important for appraisal. The primary analysis is described as involving participants who completed follow-up at 6 months, and the record does not explain participant flow or missing-data handling. This makes it difficult to assess how fully the outcome summaries represent the randomized groups.

The record illustrates why a stated sample-size calculation should be distinguished from a trial’s original design and from observed power. The calculations are characterized as planning illustrations using the observed effect and specified assumptions. The registry record does not report the original sample-size justification. Planning assumptions cannot substitute for the comparative effect estimate and uncertainty needed to interpret a completed trial.

Finally, the named secondary outcomes are not accompanied by reported analyses, and the safety summaries use different group counts from the primary outcome. Together, these features show why statistical interpretation depends not only on the direction of the posted estimates but also on analysis populations, uncertainty, missingness, and the completeness of the reported results.

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 registry record does not provide a comparative estimate or inferential test for the primary endpoint, stating that values were missing or not estimable for a two-arm comparison. It reports arm-level least-squares means and standard errors, but not the model specification, covariate adjustments, or confidence intervals. This prevents assessment of the magnitude and precision of the randomized contrast from the posted primary results.

The primary outcome population is described as participants who completed follow-up at 6 months. The record does not explain why the primary outcome summaries include 9 participants in the ranolazine group and 6 in the placebo group when enrollment is reported as 22. Missing-data methods, reasons for non-completion, and the analysis population definition beyond completion are not reported.

The registry lists two secondary outcomes but does not report their analyses. It also does not report whether multiplicity was addressed. For safety, the numbers at risk differ from the primary outcome counts, and the record does not explain the difference. The serious-event descriptions do not provide detailed timing, collection procedures, or event-level context.

Further trial details—including the randomization procedure, masking roles, and statistical analysis plan—are not reported in the registry record. The record also does not report the rationale for the sample size or details needed to reproduce the planning calculations. These gaps limit independent evaluation of the trial’s conduct and analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Targeting Right Ventricle in Pulmonary Hypertension Gilead — NCT02829034.
• Registry record last updated 2019-02-26; status last verified 2019-02.
• Results first posted 2019-02-26.
• 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

NCT02829034 is a completed, randomized, quadruple-masked, parallel-group, multicenter Phase 4 study sponsored by the University of Pennsylvania. It enrolled 22 participants with pulmonary hypertension and right ventricular dysfunction, comparing ranolazine with placebo.

The primary outcome was absolute change from baseline in MRI-assessed right ventricular ejection fraction at 26 weeks. The registry reports arm-level least-squares mean changes of 7.56 for ranolazine and -3.99 for placebo, with standard errors of 1.72 and 2.23. It does not report a two-arm comparison estimate or inferential test. Two secondary outcomes are named, but their analyses are not reported.

The record describes a primary outcome population of participants who completed follow-up at 6 months and does not explain participant flow or missing-data handling. Safety summaries report serious adverse events, other adverse events, and deaths, but do not provide a comparative safety analysis. Statistical and design details needed for a fuller appraisal are not reported in the registry record.