The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension (NCT03273387), a randomized phase 2, phase 3 study. The primary outcome is Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention.

2. Clinical Question

The question is about a measured change in right ventricular function, not a comparison of survival or a direct assessment of every aspect of pulmonary hypertension. The registry also lists functional capacity and cardiac fibrosis as secondary outcomes. It does not report the name or direction of the functional-capacity scale in the posted outcome description. The clinical question therefore needs to be read narrowly: the primary comparison is the between-group difference in average change in RVEF over the stated follow-up period.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group trial, with phase listed as phase 2 and phase 3. The sponsor is Universitas Indonesia. The study is marked completed. Its start date is 2017-09-10, and its primary completion date is 2018-11-01. The official title identifies National Cardiovascular Center Harapan Kita Hospital in Indonesia.

The intervention was trimetazidine 35 mg twice daily for 3 months in addition to regular pulmonary arterial hypertension-specific therapy. The comparator was a placebo oral capsule twice daily for 3 months, also added to regular therapy. The registry reports equal assignment of 13 participants to each group. Its primary-outcome description says that 6 patients did not complete the study and identifies two deaths due to right ventricular failure, one withdrawal from the trimetazidine group due to atypical angina, and a withdrawal from the placebo group; the description of the latter reason is incomplete in the registry record. The posted primary-outcome analyses include 10 patients in each group.

“Quadruple” is the registry’s masking label. Which participant, clinician, assessor, or other roles were masked is not reported in the registry record. The randomization method, allocation concealment procedure, original sample-size justification, and planned statistical analysis are also not reported in the registry record. The registry gives the treatment schedules and the outcome time points, but it does not give further details on adherence, treatment changes, or how missing measurements were handled. These omissions limit how fully the conduct and analysis plan can be reconstructed from the 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.

Before assignment: A total of 35 Patients were enrolled between September 2017 and November 2018 at NCCHK PAH outpatient clinic. A total of 26 patients were consent to underwent the trial and randomly assigned to receive trimetazidine or placebo with ratio 1:1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: A total 13 patients were assigned to each group equally. There were 6 patients who were not able to complete the study. A total of 2 patients from both group died due to RV failure. One patients from trimetazidine group withdrawn due to atypical angina and one patients from placebo group withdrawn due to claustrophobia.

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 Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention, measured over Baseline and 3 months after intervention.

The primary endpoint is change in right ventricular ejection fraction (RVEF) from baseline to 3 months after intervention. RVEF is the fraction of blood in the right ventricle that is ejected with each contraction; the registry reports it as a percentage and says it was assessed by cardiac MRI. The recorded change is defined as the 3-month RVEF minus the baseline RVEF. A positive change therefore represents a higher measured RVEF at follow-up than at baseline, while a negative change represents a lower measured value.

As a continuous measure, RVEF can describe the degree of change rather than reducing the result to a threshold such as improved or not improved. Comparing average change between randomized groups gives an estimate of how the groups differed over the stated period. This is a general explanation of the statistical role of a continuous endpoint; it does not establish that a measured change necessarily corresponds to a particular experience or outcome for an individual participant.

The registry’s primary outcome is specifically a cardiac MRI measure at baseline and 3 months. It does not report a threshold for a clinically important difference, nor does it explain how changes in RVEF should be interpreted alongside other measures of health. The endpoint should therefore be read as a measure of right ventricular function, in the units and timeframe stated, rather than as a complete summary of the disease or of participants’ overall outcomes.

7. Results Posted in the Registry

• Trimetazidine: mean 3.90 versus -2.80 on control; difference 6.70 (95% CI 2.40 to 11.00), standardized effect d = 1.37; z-test p = 0.002.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Changes in Functional Capacity After 3 Month Intervention

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Trimetazidine: mean 11.50 versus -17.73 on control; difference 29.23 (95% CI 16.59 to 41.87), standardized effect d = 2.03; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Trimetazidine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists two secondary outcome areas: change in cardiac fibrosis and change in functional capacity. It posts numerical results and analyses for functional capacity, but the record does not provide a posted numerical result for cardiac fibrosis. Across the posted results, the secondary functional-capacity comparison is in the same broad direction as the primary comparison in that the group means move apart in favor of a higher change in the trimetazidine group. The scale’s name, scoring direction, and clinical interpretation are not reported in the registry record, so the direction and practical meaning should not be assumed beyond the recorded numerical contrast.

This overall pattern can be considered alongside the primary RVEF result, but it does not constitute independent confirmation of a treatment effect. Both outcomes were assessed in the same trial, and the registry does not report whether the analyses were prespecified in a detailed statistical plan or whether the secondary analyses were adjusted for multiple comparisons. Looking at multiple outcomes creates more opportunities for apparently notable findings to arise by chance. Unadjusted secondary results therefore generally carry less evidential weight than a clearly prespecified primary analysis, especially when their interpretation and analysis plan are incompletely reported.

The absence of a posted numerical cardiac-fibrosis result means that no quantitative conclusion about that secondary outcome can be drawn from the registry record. The functional-capacity result may complement the primary measure conceptually, but it does not replace the primary endpoint or establish that changes in one measure explain changes in another. The registry does not report a relationship analysis between RVEF and functional capacity. In general, outcome measures can capture different aspects of a condition; concordance in direction does not by itself demonstrate a shared mechanism or a broader effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Changes in Cardiac Fibrosis After 3 Months Intervention
• Changes in Functional Capacity After 3 Month Intervention

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it records a numerical change in RVEF rather than a category. The registry reports group means and standard errors for that change, then a comparison of the two group means. A mean summarizes the central value of a group’s measurements. A standard error describes uncertainty around an estimated mean; it is not the same thing as the spread of individual participant measurements. The posted group summaries are -2.8 with standard error 1.6 for placebo, and 3.9 with standard error 1.5 for trimetazidine.

What does the mean difference represent?

The recalculated mean difference is formed by taking the placebo mean from the trimetazidine mean. It is reported as 6.7, with the contrast oriented as trimetazidine minus placebo. This gives the estimated separation between the groups’ average changes. A mean difference retains the endpoint’s original measurement scale, which makes it different from a standardized effect size. It does not show the range of individual changes, and it should not be read as a prediction for a particular participant.

What is the role of the t-test?

The sponsor’s analysis is identified as a two-sided t-test. In general, a two-sided test evaluates departures in either direction from a null hypothesis of no difference in group means. A t-test uses the observed difference and its uncertainty to assess how compatible the data are with that null hypothesis, subject to the test’s assumptions. The registry’s reported primary p-value is 0.008. The posted group summaries also permit a simple unadjusted recalculation, which gives p = 0.002. The recalculated test is not a substitute for the sponsor’s analysis; the registry does not report enough methodological detail to reconcile their results.

A p-value is not an effect estimate. It does not say how large a difference is, whether the difference matters clinically, or how likely the result is to repeat. The mean difference and interval address the estimated magnitude and uncertainty more directly. Statistical tests also rely on assumptions about the data and analysis. The registry does not report diagnostic checks or enough detail to assess those assumptions for this endpoint.

How should variability and standardized effects be read?

The recalculation reports a pooled standard deviation of 4.904 and a standardized effect size of 1.366. A pooled standard deviation combines information about variability in the groups into a common scale. Dividing a mean difference by a measure of within-group variability yields a standardized effect size in general; this expresses the contrast relative to observed variability rather than in the endpoint’s original units. It can help describe the relative scale of an effect, but it does not add independent evidence or establish clinical importance. Standardized effects can also be sensitive to variability estimates, especially when group sizes are limited.

The group summaries are reported as means and standard errors. A standard error can be used to quantify uncertainty in a mean, while a standard deviation describes how participant values vary around that mean. Those quantities answer different questions. The pooled standard deviation reported for the recalculation is not the standard error and should not be interpreted as one.

What does an interval add?

The recalculated interval for the mean difference runs from 2.401 to 11.0. In general, a confidence interval gives a range of values compatible with an estimate under a statistical procedure and its assumptions. It shows the uncertainty in the estimated contrast in the original measurement scale, which a p-value does not convey. The confidence level for this interval is not reported in the registry record, so it should not be labeled with a particular coverage percentage. The interval is a recalculation from posted summary statistics, not an interval reported by the sponsor.

The interval does not represent a range containing a specified proportion of individual participant outcomes. Nor does it include uncertainty about unreported design or analysis choices. The recorded interval should be read alongside the analysis population, missing outcome information, and the limitations of a summary-statistic recalculation.

Why distinguish reported and recalculated analyses?

The sponsor’s two-sided t-test gives p = 0.008. The unadjusted recalculation from the posted summary statistics gives p = 0.002 and an estimated mean difference of 6.7 with an interval from 2.401 to 11.0. These are not interchangeable outputs. The sponsor’s result is the inferential analysis reported in the registry; the recalculation is a transparent comparison derived from the posted group summaries. The registry does not report the sponsor’s corresponding estimate and interval or the detail needed to establish the precise source of the difference in p-values. The recalculation therefore helps readers inspect the summary data, but cannot recover unreported analytic choices or replace the trial’s reported analysis.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 6.7, with an interval from 2.401 to 11.0. This interval describes uncertainty around the estimated difference between the group averages, under the assumptions of the recalculation. Its lower and upper limits are both on the same scale as the mean difference. The confidence level is not reported in the registry record, so no coverage percentage can be attached to these limits.

The interval is not a range of likely outcomes for an individual participant, nor does it mean that every value inside it is equally plausible. In general, an interval communicates how much uncertainty surrounds an estimate; its width depends on the observed data and the statistical procedure. It should be read with the point estimate rather than in isolation. The interval does not state whether any value represents a clinically important change, because the registry does not report a clinical-importance threshold.

The posted primary analysis includes 10 participants in each group, while the registry says that 6 assigned participants did not complete the study. The record does not explain how missing primary measurements were handled or report an analysis including all assigned participants. That missing information limits interpretation of precision: an interval based on available summary statistics does not account for possible bias from missing outcomes. The interval is a recalculation, not a sponsor-reported confidence interval, and it cannot capture uncertainties arising from analytic choices that are not described in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size display gives planning illustrations based on fractions of the observed effect. Its figures are participants per arm, not total participants or total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record, so these illustrations should not be mistaken for the study’s original sample-size rationale.

The 80% power column gives the number of participants per arm estimated for an analysis to have an 80% chance of detecting the specified effect under the stated planning assumptions, if that effect were the true one. The 90% power column gives the corresponding planning number for a 90% chance. These are prospective planning quantities, not statements about the probability that the observed finding is correct. The displayed rows compare planning for 100%, 75%, and 50% of the observed effect. As the effect assumed for planning becomes smaller, more participants are needed to detect it under otherwise unchanged assumptions.

For the primary endpoint, the illustrations give 9 participants per arm for 80% power and 12 for 90% power when planning for 100% of the observed effect; for 75%, the corresponding figures are 15 and 21; for 50%, they are 34 and 46. These figures are planning calculations, not a reconstruction of enrollment targets chosen by the investigators. They are not observed power: observed power is not a useful substitute for reading the effect estimate and its uncertainty after a study has been completed. The illustrations also do not account for design features or missing-data considerations that are not included in their stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 6.700; pooled standard deviation σ = 4.904.
2. n = 2 × (1.96 + 0.842)² × 4.904² / 6.700² = 8.4, rounded up to 9 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 6.7                      # observed difference in means
sigma <- 4.90407993409569                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3273387)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 9 (80% power), 12 (90% power)
 75% of observed effect: n per arm = 15 (80% power), 21 (90% power)
 50% of observed effect: n per arm = 34 (80% power), 46 (90% power)
power.t.test: 9.5 
Simulated power at n = 9 per arm: 0.773 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis is a two-sided t-test with p = 0.008. The registry does not report a sponsor-estimated mean difference or confidence interval for the primary outcome. A separate unadjusted recalculation from the posted group summaries gives a mean difference of 6.7, an interval from 2.401 to 11.0, and p = 0.002.

The recalculation is based on the group means, standard errors, and analyzed group sizes recorded for the outcome. It is a simple summary-statistic analysis and should not be assumed to reproduce every choice in the sponsor’s analysis. The registry does not state enough about the sponsor’s model, variance assumptions, or handling of missing data to explain the difference between the reported and recalculated p-values. The recalculation does not establish that the sponsor’s test is incorrect, nor does it supply an unreported sponsor effect estimate.

For interpretation, retain the sponsor’s reported p-value as the result of the sponsor’s own analysis, while treating the recalculated estimate and interval as an additional, unadjusted reading of the posted summaries. Both should be understood in the context of the small analyzed groups and the incomplete reporting of outcome handling. Neither p-value alone establishes the magnitude, clinical importance, or generalizability of the observed group contrast.

15. Multiplicity, Missing Data and Analysis Populations

The registry names one primary outcome and two secondary outcome areas, and it posts three analyses. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a detailed statistical analysis plan. When several outcomes are examined, the chance of finding at least one apparently unusual result can increase if each is tested without accounting for the number of analyses. This is a general statistical concern, not evidence that any particular result is false. Without a reported multiplicity plan, secondary p-values should be interpreted cautiously and should not be treated as if they were protected by a prespecified family-wise testing procedure.

The primary-outcome description states that 13 patients were assigned to each group and that 6 patients did not complete the study. It describes two deaths due to right ventricular failure, a withdrawal from the trimetazidine group due to atypical angina, and a withdrawal from the placebo group; the latter description is incomplete in the registry record. The posted primary outcome analysis includes 10 patients per group. The registry does not explain whether the analysis used all available observations, how missing measurements were handled, or whether any imputation or sensitivity analysis was conducted.

Random allocation can support a fair comparison when participants are analyzed in a way that preserves the assigned groups, but the registry does not state whether the primary analysis followed an intention-to-treat principle. The analysis population, handling of withdrawals and deaths, and any exclusion rules are not reported in enough detail to determine this. Missing outcomes can reduce precision and, depending on why data are missing and how they are handled, can also affect the estimated comparison. The record does not provide information to assess those possibilities.

The registry’s quadruple-masking label does not identify which roles were masked, and the method of randomization and allocation concealment is not reported. These details, along with the unavailable original analysis plan, limit assessment of bias and selective reporting. Such reporting gaps do not by themselves show that the conduct was flawed; they mark questions the registry record cannot answer.

16. 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: cardiovascular mortality (15.4%).

The registry reports serious adverse events among 13 participants at risk in each group. It records 2 participants affected in the sugar-pill group and 2 in the trimetazidine group. For other adverse events, it records 1 affected participant in the sugar-pill group and 2 in the trimetazidine group. The registry also records 2 deaths in each group. These are descriptive counts as posted; they should not be added together because the record does not clarify whether event categories overlap or whether counts refer to unique participants across categories.

“Cardiovascular mortality” is listed as a top serious-event term with 15.4%. The record does not make clear whether this percentage is group-specific or how it relates to the death counts, so it should not be attributed to either group. The primary-outcome description separately states that two patients from both groups died due to right ventricular failure. The safety information does not establish that treatment caused or prevented any event. Event definitions, timing, severity grading, and a detailed account of attribution are not reported in the registry record. These figures are therefore best read as recorded safety information, not as a precise comparative estimate of risk.

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

The posted primary results show different average changes in RVEF between the randomized groups over 3 months. The recalculated mean difference is 6.7, with an interval from 2.401 to 11.0; the sponsor reports p = 0.008 from a two-sided t-test. Those statistics describe an observed group-level comparison in the analyzed participants. They do not show that every participant changed in the same way, and they do not establish the result that would occur in another population or setting.

The primary endpoint is a cardiac MRI measure of right ventricular function. The registry does not report a threshold for a clinically important change in RVEF, and it does not give enough context to translate the numerical difference into a judgment about participants’ overall health. The functional-capacity outcome is also posted, but the scale and its scoring direction are not reported. Cardiac fibrosis is listed as a secondary outcome without a posted numerical result. Each outcome addresses a distinct measure, and the record does not establish how these measures relate to one another.

The result does not establish a survival effect, a long-term effect, or an effect on outcomes not measured in the record. Follow-up for the primary endpoint is at baseline and 3 months after intervention. The number of participants analyzed for the primary outcome is limited, and the registry reports incomplete study completion without explaining how missing outcomes were handled. The interval and p-values also do not resolve uncertainty about unreported analysis choices or multiplicity.

Statistical evidence for a difference is not the same as evidence of clinical importance. A p-value is not the probability that the treatment is beneficial, and a confidence interval is not a guarantee about the true value. The record supports a careful description of the observed contrast and its uncertainty, but not a broader claim about how treatment should be used or what an individual should expect.

18. Why This Trial Matters Statistically

This trial offers a randomized comparison of a continuous cardiac MRI measure between trimetazidine and placebo, with both groups continuing regular pulmonary arterial hypertension-specific therapy. The primary outcome is defined as change from baseline to 3 months, so the reported contrast directly concerns change over a specified follow-up period rather than a single follow-up measurement alone. The randomized parallel-group structure provides a framework for comparing group outcomes, although details of the randomization process and analysis population are not reported.

The record also illustrates why estimates, uncertainty intervals, and p-values should be read together. The recalculated mean difference expresses the contrast on the endpoint scale, while its interval conveys uncertainty under the recalculation’s assumptions. The sponsor’s reported test result and the unadjusted recalculation are not identical outputs. Keeping those roles distinct avoids treating a single p-value as a complete account of the evidence.

Several statistical questions remain visible in the record: incomplete follow-up, a difference between the sponsor-reported and recalculated p-values, secondary outcomes with limited reporting, and no reported multiplicity plan. These issues do not erase the observed result, but they affect how confidently it can be interpreted and how broadly it can be generalized. The case is useful for seeing how registry results can support a transparent summary while leaving important design and analysis details unresolved.

Most importantly, the trial’s posted data concern a particular outcome, population, treatment schedule, and follow-up period. Statistical interpretation requires keeping those boundaries in view. The result can be described without turning it into a claim about outcomes or populations the registry does not report.

19. 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 primary analysis includes 10 participants per group, while the registry reports 13 assigned to each group and says 6 patients did not complete the study. The description of one placebo-group withdrawal is truncated, and the record does not explain how missing primary-outcome data were handled. It does not report whether all assigned participants were included in the analysis or provide sensitivity analyses for incomplete outcomes. These gaps make it difficult to assess whether the analyzed groups reflect the original randomized groups.

The registry identifies a randomized, quadruple-masked design but does not report the sequence-generation method, allocation concealment, or which roles were masked. It also does not report the original sample-size justification or a detailed statistical analysis plan. The reported primary p-value is 0.008, while an unadjusted recalculation from posted summaries gives p = 0.002; the record lacks detail needed to explain the difference. The recalculated interval’s confidence level is not reported.

There is no reported multiplicity strategy for the primary and secondary outcomes. The registry lists cardiac fibrosis as a secondary outcome but gives no numerical result for it, and the functional-capacity scale is not identified or explained. The follow-up period for the primary outcome is 3 months, so the record does not establish longer-term outcomes. It also does not report a clinically important threshold for RVEF change or enough safety detail to clarify the relation between event categories, deaths, and the listed cardiovascular-mortality term.

These are limitations of what can be established from the registry record. They do not, on their own, show that the trial was conducted improperly or that a particular result is biased. They define the uncertainty that remains when interpreting the posted results.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension — NCT03273387.
• Registry record last updated 2019-10-03; status last verified 2019-09.
• Results first posted 2019-10-03.
• 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.

23. Record Summary

NCT03273387 is a completed randomized, quadruple-masked, parallel-group study listed as phase 2 and phase 3. The registry names Universitas Indonesia as sponsor and identifies precapillary pulmonary hypertension as the condition. It reports 26 enrolled participants, with 13 assigned to each group. Trimetazidine 35 mg twice daily for 3 months was compared with placebo twice daily for 3 months, both on top of regular pulmonary arterial hypertension-specific therapy.

The primary outcome was change in RVEF by cardiac MRI from baseline to 3 months. The posted analysis includes 10 participants per group. The sponsor reports a two-sided t-test p-value of 0.008; a separate unadjusted recalculation from the posted summaries gives a mean difference of 6.7, an interval from 2.401 to 11.0, and p = 0.002. Functional capacity is also reported as a secondary outcome, while the registry lists cardiac fibrosis without a numerical result. Missing-data handling, the original sample-size justification, and a detailed statistical analysis plan are not reported in the registry record.