REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension (NCT02310672), a na phase 4 study. The primary outcome is Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26.

2. Clinical Question

3. Trial Design

The registry record describes REPAIR as a prospective, multicenter, single-arm, open-label, Phase 4 study. Enrollment was 89, and the study status is completed. The recorded start date is 2015-06-01, and the primary completion date is 2019-09-10. All participants were assigned to the same open-label macitentan regimen, 10mg o.d.; there was no randomized allocation or masking. The registry record therefore describes a treatment cohort rather than a controlled comparison.

The study evaluated right ventricular and hemodynamic properties in people with symptomatic pulmonary arterial hypertension. Right heart catheterization was scheduled at baseline and Week 26. Cardiac magnetic resonance imaging was scheduled at baseline, Week 26 and Week 52. The primary outcome focuses on the baseline-to-Week 26 change in right ventricular stroke volume. Other listed outcomes include right ventricular end diastolic volume, right ventricular end systolic volume, right ventricular ejection fraction, right ventricular mass, six-minute walk distance and World Health Organization functional class, each with a Week 26 change outcome.

The brief summary describes treatment for 1 year and safety monitoring throughout the study. It also describes three optional sub-studies: metabolism with PET-MR scans, biopsy during right heart catheterization, and echocardiography. Each patient could participate in no sub-study or in one sub-study. The number participating in each sub-study is not reported in the registry record.

The primary outcome description says the primary analysis was based on interim results as pre-planned and that the primary outcome data table was finalized as is. Details of the interim analysis, including its timing and statistical procedures, are not reported in the registry record. A detailed statistical analysis plan, including any covariate adjustment or missing-data procedures, is also not reported.

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: Total 112 participants were screened out of them 89 participants were enrolled in the study and of which 87 participants received study medication. Two participants who did not receive study treatment were wrongly classified as enrolled by the sites.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Modified full analysis set (mFAS) included of all screened participants who received at least one dose of study drug and who had a baseline as well as a post-baseline measurement taken between 16 weeks and 30 weeks of treatment.

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: Safety Set included all screened participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26, measured over Baseline and Week 26.

The primary endpoint is change from baseline in right ventricular stroke volume at Week 26, measured in milliliters by cardiac magnetic resonance imaging using pulmonary artery flow. Stroke volume represents the volume of blood ejected by the ventricle with each heartbeat. In general, it is one measure of ventricular pumping and can be considered alongside other measures of right ventricular size and function.

A change endpoint compares a participant’s post-baseline measurement with that participant’s baseline measurement. This can describe how the measured quantity changed over the study interval. The registry record identifies the reported statistic as a least-squares mean and its dispersion as a standard error. A least-squares mean is generally a model-based mean; however, the model details and any adjustment variables are not reported in the registry record. The standard error describes the precision of an estimated mean, rather than the spread of individual participant measurements.

The primary endpoint is useful for describing a measured aspect of right ventricular function over time. It is not, on its own, a direct comparison against an untreated or alternative-treatment group. The registry record’s endpoint description does not include the numerical mean change, its standard error, a confidence interval or a p-value. Those quantities are not reported in the registry record, so the size and precision of the observed primary outcome cannot be characterized from the available outcome details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record labels the primary outcome statistic a least-squares mean and its dispersion a standard error. These terms describe different features of an estimate. A mean summarizes the central value of a continuous outcome. A least-squares mean is generally a mean estimated from a statistical model, potentially conditional on model terms. The record does not describe the model, its covariates or the assumptions used to obtain the estimate, so further claims about adjustment cannot be made.

What does a standard error describe?

In general, a standard error quantifies the uncertainty in an estimated statistic due to sampling variation under a statistical model. It is not the same as the standard deviation of individual measurements: the standard deviation describes variation among observations, while a standard error describes uncertainty in an estimate. A smaller standard error generally indicates a more precise estimate under the model, but interpretation also depends on the model and the data used. The registry record identifies standard error as the reported dispersion for the primary outcome but does not give its value.

A confidence interval is a range constructed by a statistical procedure to express uncertainty around an estimate. In general, the interval’s width depends on the estimate’s uncertainty and the procedure used to calculate it. A narrow interval indicates greater precision than a wide interval under the same approach. Because neither an interval nor the numerical standard error is reported in the registry record, the precision of the primary mean change cannot be assessed. A p-value, if reported, would address compatibility of the data with a specified null hypothesis under stated assumptions; it would not quantify the size or clinical importance of an effect. No primary p-value is reported in the registry record.

Why does the single-group design matter?

For a continuous endpoint measured at baseline and follow-up, the study can summarize within-participant change and then estimate a group mean change. The registry record identifies the target comparison as baseline to Week 26. With only one treatment group, the mean change does not estimate a randomized difference between macitentan and a control condition. General influences over time and measurement variability remain possible explanations for observed change. Open-label conduct also means that participants and study personnel were not masked, although the primary endpoint is based on imaging. The record does not describe whether image readers were masked or how image measurements were standardized.

The primary endpoint is a continuous measurement in milliliters. General methods for continuous outcomes can estimate average change, but distributional assumptions, outliers and missing follow-up measurements can affect results. The registry record does not report diagnostic checks, transformations, robust methods or other model details. It is therefore not possible to determine which assumptions were assessed or how departures from them were handled. General statistical explanations do not establish which specific procedure the investigators used.

What do the analysis population and timing specify?

The modified full analysis set is defined as screened participants who received at least one dose and had a baseline plus a post-baseline measurement taken between 16 weeks and 30 weeks of treatment. This definition makes treatment exposure and measurement availability relevant to inclusion in the primary analysis. The size of this population and the number excluded under each part of the definition are not reported in the registry record. The outcome timeframe is Baseline and Week 26, while the eligibility window for a post-baseline measurement spans 16 weeks to 30 weeks of treatment. The record does not give further detail about handling measurements taken at different times within that window.

The primary outcome description states that the primary analysis was based on interim results as pre-planned and that the primary outcome data table was finalized as is. In general, an interim analysis is an analysis conducted before all planned follow-up is complete. Its existence can matter for interpretation if repeated examination of accumulating data affects statistical procedures. The registry record does not describe the interim timing, decision rules, any adjustment to statistical thresholds, or whether those procedures affected the final inference. Those details cannot be inferred from the statement that interim results were pre-planned.

How should planning illustrations be read?

General sample-size planning asks how many participants would be needed for a specified power to detect an assumed effect under stated statistical conditions. Such planning depends on assumptions about the effect, variability, significance level, allocation and analysis method. Planning illustrations are not observed results and do not indicate the power actually achieved by a completed study. The planning description associated with this study specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set to a stated fraction of the observed effect. For time-to-event outcomes, it describes total events; for other outcomes, it describes participants per arm. These assumptions do not convert this single-group study into a two-arm trial, and the illustration is not the study’s own design justification. The trial’s sample-size justification is not reported in the registry record.

Because the numerical primary estimate and its uncertainty are not reported in the registry record, no recalculated unadjusted estimate or independent comparison can be described. In general, recalculations from summary statistics can be useful as checks, but they are not substitutes for a prespecified sponsor analysis or a full analysis of participant-level data. No recalculated result is reported for this outcome.

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("Macitanten 10 mg")
n   <- c(42)
m   <- c(15.17)
sp  <- c(2.75)
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  Macitanten 10 mg  42  15.170  17.822  9.616  20.724

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists eight outcome measures, including the primary outcome and secondary measures of right ventricular volumes, ejection fraction and mass, six-minute walk distance and World Health Organization functional class. When several outcomes are examined, the chance of at least one apparently unusual result can increase if each is tested separately without an appropriate strategy. In general, multiplicity procedures can control error rates or distinguish confirmatory outcomes from exploratory ones. The record does not report a multiplicity adjustment, testing hierarchy or other plan for interpreting several outcomes together. It is therefore not possible to determine how the family of outcomes was handled statistically.

The registry record’s analysis summary reports zero analyses. This does not supply outcome-level estimates, confidence intervals or p-values. The primary outcome description says the analysis used interim results as pre-planned and that the primary outcome data table was finalized as is, but details of interim monitoring and any adjustments are not reported. The statistical plan and the reason for the reported analysis summary are not described in the registry record.

The primary analysis population is the modified full analysis set. It includes screened participants who received at least one dose and had both baseline and a post-baseline measurement between 16 weeks and 30 weeks of treatment. The record does not state the size of that set, how many participants lacked measurements, why any measurements were missing, or how missing values were handled. Methods such as complete-case analysis, imputation or likelihood-based approaches have different assumptions; none should be attributed to this study without documentation. The number enrolled is not a substitute for the number analyzed, and the registry record does not provide enough detail to assess the impact of missing primary outcome data.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (3.4%), acute myocardial infarction (2.3%), sepsis (2.3%), pulmonary arterial hypertension (2.3%), pulmonary embolism (2.3%).

The registry record lists 87 participants at risk for serious adverse events and 15 affected in that category. It also lists 87 at risk for other adverse events and 57 affected in that category. One death is recorded. These are descriptive safety counts for the macitentan 10 mg group; the record does not provide a control group for comparison. A count does not by itself establish whether an event was caused by study treatment, and the registry entries do not attribute individual events to treatment.

The most frequently listed serious adverse event terms are pneumonia at 3.4%, acute myocardial infarction at 2.3%, sepsis at 2.3%, pulmonary arterial hypertension at 2.3%, pulmonary embolism at 2.3% and anaemia at 1.1%. These percentages are reproduced as listed in the registry record. They should be read as event-term summaries, not as evidence that the listed events were caused by macitentan. The record does not provide additional details about event timing, duration, severity beyond the serious-event classification, or individual clinical circumstances. Safety findings from a single treatment group describe events recorded during the study but cannot establish comparative risk against an untreated or alternative-treatment group.

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

The study’s statistical question is clear: it aimed to describe the change in right ventricular stroke volume from baseline to Week 26 among participants receiving open-label macitentan. The registry record specifies cardiac magnetic resonance imaging using pulmonary artery flow as the measurement approach and identifies a least-squares mean with standard error as the intended summary. It also gives a definition for the modified full analysis set. Those details explain the outcome and the intended analysis population, but they do not provide the numerical result.

The primary mean change, standard error, confidence interval and p-value are not reported in the registry record. Accordingly, the result’s direction, magnitude and precision cannot be evaluated from the available record. It is not possible to say whether the mean change was positive or negative, how variable the estimate was, or whether a statistical test crossed any specified threshold. A missing numerical result must not be interpreted as no change, as a null finding or as evidence of benefit or harm.

Even if a numerical before-and-after change were available, the single-arm design would limit causal interpretation. A change observed during treatment is not the same as a treatment effect estimated by comparison with a concurrent control group. Without such a comparison, changes over time could reflect treatment, the course of the condition, other factors or measurement variability. The open-label design adds further context: masking was absent, and the record does not describe masking of image assessors.

The listed secondary outcomes and safety counts provide context for what the study monitored, but their presence does not resolve the missing primary estimate or create a controlled comparison. The registry reports enrollment of 89, while the number in the defined primary analysis population is not reported. The record also does not report missing-data procedures or detailed multiplicity methods. These gaps limit assessment of precision, selection into analysis and the interpretation of multiple outcomes.

The appropriate statistical reading is therefore bounded: the record documents a completed Phase 4 single-group study and its primary measurement strategy, but it does not report the primary numerical result needed to characterize observed change. It does not establish a comparison with another treatment or control condition.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a well-defined measurement question and a reported statistical result. The registry record identifies a continuous primary endpoint, its time point, measurement method, summary statistic and dispersion measure. Those elements help readers understand what was intended to be estimated. Yet without the mean change and its uncertainty, readers cannot assess either the observed direction or precision. Clear endpoint definitions do not replace reporting the estimate.

It also illustrates why design is central to interpretation. A prospective, multicenter study can collect measurements on a planned schedule, but a single-arm design remains a within-group observation rather than a controlled treatment comparison. Baseline measurements can provide a reference for describing change; they do not provide the counterfactual outcome that a comparison group could help estimate. Statistical summaries cannot remove that design limitation.

The study’s primary analysis population definition is another important statistical detail. Requiring treatment exposure and measurements in a follow-up window determines who can contribute to the primary outcome analysis. Enrollment alone does not indicate how many participants contributed, and the registry record does not report the analysis-set size. Reporting participant flow, missingness and the handling of unavailable measurements would help readers judge how representative the analyzed data are.

Finally, the record lists multiple outcomes and states that the primary analysis used interim results as pre-planned, but does not describe the relevant statistical procedures. Multiplicity and interim analysis can affect how uncertainty and evidence are interpreted. This makes transparent reporting of the analysis plan, outcome estimates and uncertainty especially important. The available record allows a precise description of the design and intended endpoint, while leaving the key numerical primary finding and several analytic details unreported.

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 principal limitation for statistical interpretation is that the registry record does not report the numerical primary outcome estimate or its uncertainty. The primary outcome is identified as a least-squares mean change with standard error, but neither statistic is given, and no confidence interval or p-value is reported. The primary result therefore cannot be described in terms of direction, size or precision.

The single-arm, open-label design has no concurrent control group. Any baseline-to-Week 26 change would describe the observed study cohort and would not, by itself, distinguish treatment-associated change from other influences over time. The record does not report masking, if any, of those reading or processing the cardiac magnetic resonance imaging measurements.

Although enrollment is reported as 89, the number included in the modified full analysis set is not reported. The set requires receipt of at least one dose and measurements at baseline and between 16 weeks and 30 weeks of treatment. Without the analysis-set count, participant flow and reasons for missing measurements, it is not possible to assess how much data contributed to the primary endpoint or whether missingness could affect interpretation. Missing-data methods are not reported in the registry record.

The primary outcome description notes that the analysis was based on interim results as pre-planned and that the outcome data table was finalized as is. Details of interim procedures are not reported. The record also lists multiple outcome measures but does not describe multiplicity handling, model specifications or the sample-size justification. These omissions limit assessment of the statistical framework beyond the stated endpoint summary. They do not establish that a particular procedure was or was not used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension — NCT02310672.
• Registry record last updated 2025-03-30; status last verified 2025-03.
• Results first posted 2020-09-24.
• 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

REPAIR is recorded as a completed, prospective, multicenter, single-arm, open-label, Phase 4 study of macitentan in symptomatic pulmonary arterial hypertension. Enrollment was 89. All participants received open-label macitentan 10mg o.d., with treatment described for 1 year. The primary outcome was change from baseline in right ventricular stroke volume at Week 26, measured by cardiac magnetic resonance imaging from pulmonary artery flow. Its stated summary is a least-squares mean with standard error.

The primary outcome description says the analysis used interim results as pre-planned and that the outcome data table was finalized as is. The numerical primary estimate and its uncertainty are not reported in the registry record. The record defines the modified full analysis set but does not report its size. There was no control group. Safety listings include 15 affected by serious adverse events, 57 affected by other adverse events, and one death among the recorded group details.