This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension (NCT03528902), a randomized phase 2 study. The primary outcome is Transthoracic Echocardiogram (ECHO)-Based Change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) Measurement.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03528902 |
| Phase | Phase 2 |
| Condition | Hypertension, Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanderbilt University Medical Center |
| Results posted | Yes |
2. Clinical Question
This trial was designed to examine the feasibility and effects of tamoxifen in people with pulmonary arterial hypertension (PAH). The registry describes assessment of tolerability, functional condition, and selected biomarkers, alongside echocardiographic measurements and other clinical and quality-of-life measures. The central registered outcome was change in tricuspid annular plane systolic excursion (TAPSE) from Week 0 to Week 24.
Population
Subjects with pulmonary arterial hypertension. The registry record does not report further eligibility details in the information available for this trial.
Intervention
Tamoxifen, described as 20 mg po TID for 24 weeks.
Comparator
Placebo oral tablet. A dose or other administration details for the placebo are not reported in the registry record.
Primary question
What change in TAPSE, measured by transthoracic echocardiogram, occurred from Week 0 to Week 24 in the tamoxifen and placebo arms?
The registry also lists six-minute walk test distance and quality of life assessed with the SF36 and emPHasis-10 questionnaires. Those measures provide context about functional status and patient-reported quality of life, while TAPSE is the registered primary outcome. Although the trial is marked completed, numerical results for the primary outcome and these secondary measures are not reported in the registry record. The posted information therefore establishes the question and planned measurement schedule, but does not permit a comparison of observed changes between the arms.
3. Trial Design
This was a phase 2, randomized, quadruple-masked, parallel-arm trial sponsored by Vanderbilt University Medical Center. The registry lists an enrollment of 18 and identifies tamoxifen and placebo oral tablet as the interventions. The tamoxifen arm is described as 20 mg po TID for 24 weeks; the placebo description is simply “Placebo arm.” Allocation concealment procedures, the identities of the masked parties, and further operational details are not reported in the registry record.
The study is marked completed. Its recorded start date is 2018-10-01, and its primary completion date is 2023-06-14. These dates describe registry milestones; they do not establish when all analyses were completed or when results became available.
The primary outcome was change in TAPSE from Week 0 to Week 24, measured with transthoracic echocardiography. The registry describes the outcome as a mean with standard deviation and gives a 24-week timeframe. Secondary outcomes include six-minute walk test distance and two quality-of-life assessments: SF36 and emPHasis-10, each administered at baseline and 12 and 24 weeks. The record also describes evaluation of selected biomarkers, functional condition, tolerability, hormone levels, and other echocardiographic parameters.
Enrollment is a planned or recorded trial-level count, not a substitute for the number analyzed for a particular outcome. Outcome-specific denominators, adherence, withdrawals, and analysis populations are not reported in the registry record. The randomized design can support a comparison between assigned arms when outcome data and an appropriate analysis are available. Without posted numerical primary-outcome results, the registry record alone cannot establish the magnitude or precision of any treatment contrast.
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
| Stage | Tamoxifen | Placebo |
|---|---|---|
| STARTED | 9 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Tamoxifen | Placebo |
|---|---|---|
| Adverse Event | 1 | 0 |
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.
| Characteristic | Unit | Tamoxifen | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 9 | 18 | |
| Age, Continuous | years | 45.8 (SD 12.4) | 51 (SD 10.5) | 48.4 (SD 11.4) |
| Sex: Female, Male: Female | Participants | 9 | 8 | 17 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 8 | 9 | 17 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 8 | 8 | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 9 | 9 | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Transthoracic Echocardiogram (ECHO)-Based Change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) Measurement, measured over 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mm |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in tricuspid annular plane systolic excursion (TAPSE) between Week 0 and Week 24. TAPSE is measured using transthoracic echocardiography and is reported in millimeters. The registry describes the endpoint as a mean, with standard deviation as its dispersion measure. In general, a change endpoint compares a participant’s measurement at follow-up with that participant’s measurement at baseline; the registered comparison is over the 24-week intervention period.
The registry characterizes TAPSE as a measure of global right ventricular function, describing apex-to-base shortening of the ventricle. It also states that the measurement is obtained with an echocardiogram that can be performed on a resting subject without sedation in an outpatient setting. The record notes that TAPSE correlates closely with right ventricular ejection fraction and has been determined to be highly specific and easy to measure. These points explain why the measure may be useful as a cardiac-function indicator; they do not establish that a change in TAPSE necessarily corresponds to a change in how a participant feels or functions.
The primary endpoint is clinically interpretable only alongside the actual arm-specific results, their variability, and the estimated between-arm contrast. Those numerical outcome results are not reported in the registry record. The listed measurement plan therefore defines what the trial set out to assess, but does not show the observed direction, size, or precision of change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes a randomized comparison of tamoxifen with placebo in a phase 2 trial, with change in TAPSE over 24 weeks designated as the primary outcome. It does not report numerical results for that endpoint. In particular, the posted record does not give arm-specific mean changes, a between-arm estimate, a confidence interval, or a test result for the primary comparison. The direction, magnitude, and precision of the primary-outcome contrast are therefore not reported in the registry record.
The same limitation applies to the listed secondary outcomes. Six-minute walk test distance and the SF36 and emPHasis-10 quality-of-life assessments are identified, but outcome values and between-arm analyses are not reported in the registry record. The brief summary mentions evaluation of functional condition, selected biomarkers, hormone levels, and other echocardiographic parameters; numerical findings for these measures are also not reported in the registry record. No conclusion about differences between arms on these measures can be drawn from the record alone.
The trial is marked completed, and its enrollment is listed as 18. Completion status and enrollment do not supply evidence about the primary endpoint. Nor does the absence of numerical findings establish that the observed effect was absent, favorable, unfavorable, or clinically important. It means that the registry record does not provide the estimates required to make those judgments.
General statistical interpretation depends on both the estimated treatment contrast and its uncertainty. A confidence interval, when reported, describes a range of values compatible with the data under the analysis assumptions; it helps readers assess precision rather than merely whether a threshold was crossed. A p-value, if reported, addresses compatibility of the data with a specified null model, not the size or importance of an effect. Neither statistic is reported for the primary outcome in this registry record.
The trial’s modest recorded enrollment makes careful attention to uncertainty especially relevant, but no result should be inferred from enrollment alone. Small studies can produce imprecise estimates, and the actual precision depends on observed variability, available outcome data, and the analysis. Those details are not reported in the registry record. The appropriate statistical reading is therefore descriptive: the registry specifies a randomized design and an outcome question, but it does not post the primary estimates needed to judge the comparison.
9. Statistical Methods Explained
The registry describes a randomized, parallel-arm comparison with quadruple masking. Randomization is intended to make assignment independent of measured and unmeasured participant characteristics on average. It does not guarantee that the groups are identical, particularly in a trial with an enrollment of 18. Masking can reduce the influence of expectations on care, measurement, and reporting, but the record does not specify which participants or study personnel were masked or how masking was maintained.
What does the primary outcome summarize?
TAPSE is a continuous measurement in millimeters, and the primary outcome is its change from Week 0 to Week 24. A mean summarizes the center of a set of measurements. The standard deviation describes how dispersed individual values are around that mean; it is not the same as the uncertainty around a group mean or around a treatment contrast. Reporting a mean and standard deviation can describe outcome distributions, but a between-arm estimate and a measure of its uncertainty are needed to interpret the randomized comparison.
In general, an analysis of change can compare average changes between randomized arms, or it can use a model that accounts for baseline measurements and other prespecified features. These approaches can differ in their assumptions and precision. The statistical plan and the method used for the primary analysis are not reported in the registry record. It is therefore not possible to identify which approach was used or whether the posted outcome, if any, follows a prespecified analysis.
How should uncertainty be read?
In general, a confidence interval expresses the precision of an estimate under the model and data assumptions. A narrower interval indicates greater precision than a wider interval, while the interval’s location helps show which effect sizes are compatible with the data. A p-value is a measure of how unusual the observed data, or more extreme data, would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not report a confidence interval or p-value for the primary outcome.
Interpretation also depends on the scale of the endpoint. A difference in millimeters can be compared with clinical context only if an appropriate threshold or interpretation is available. Such a threshold is not reported in the registry record. General considerations about effect size therefore cannot establish the relevance of an unreported TAPSE contrast.
What can a planning illustration tell readers?
Sample-size illustrations are planning calculations, not evidence that a trial had a particular probability of detecting an effect. The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a stated fraction of the observed effect. The illustrations are described as being computed from the observed effect, rather than as the trial’s own design justification. They must not be read as observed power or as evidence that the study was adequately powered. A sample-size justification in the trial protocol is not reported in the registry record.
More generally, power calculations depend on assumptions about the effect to detect, variability, allocation, and analysis. When calculated from an observed effect, planning illustrations are conditional on that estimate and can be unstable, especially when the estimate is imprecise. They do not change the evidential content of the trial or replace the reported estimate and confidence interval. Specific sample-size illustration values are not reported in the registry record information described for this trial.
Why do analysis details matter?
For a randomized study, an intention-to-treat analysis generally compares participants according to assigned arm, regardless of adherence, while a per-protocol analysis applies additional criteria related to following the intervention. These are general concepts, not a description of the analysis used in this trial. The analysis population, handling of adherence, missing measurements, covariate adjustment, and statistical model are not reported in the registry record. Without those details and the numerical results, readers cannot assess whether the analysis preserved the randomized comparison or how sensitive conclusions might be to analytic choices.
The registry indicates six outcome measures and zero analyses in its posted analysis information. The primary outcome is not reduced to a single comparison in the registry record because it has several categories or time points. Consequently, no single numerical treatment estimate can be interpreted from the posted results. Statistical interpretation should remain limited to the registered design and measurement plan, with the absence of posted estimates made explicit.
10. Multiplicity, Missing Data and Analysis Populations
The record lists multiple outcomes and assessment times: the primary TAPSE change over 24 weeks, six-minute walk test distance, and SF36 and emPHasis-10 quality-of-life assessments at baseline and 12 and 24 weeks. The brief summary also refers to biomarkers, hormone levels, and additional echocardiographic parameters. When multiple outcomes or time points are assessed, the chance of at least one apparently noteworthy result can increase if each is tested independently. General approaches include prespecifying a primary comparison, adjusting for multiple testing, or treating secondary analyses as exploratory. The multiplicity strategy for this trial is not reported in the registry record.
The primary outcome is identified, but the registry does not give a single numerical primary comparison. Its record notes that the endpoint has several categories or time points and is not reduced to one comparison. The number and organization of outcome analyses are not reported beyond the posted analysis count of zero. It is not possible to determine whether any planned adjustment for multiplicity was used.
Missing-data methods and outcome-specific denominators are not reported in the registry record. The record does not describe whether missing measurements occurred, how they were handled, or whether sensitivity analyses were conducted. The analysis populations, including whether results were planned or reported for all randomized participants, are also not reported in the registry record. These omissions matter because missing follow-up can affect both precision and the validity of comparisons, depending on its amount and pattern and on the analysis assumptions. No conclusion about the effect of missing data can be drawn without those details.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tamoxifen | 0 | 9 | 0.0% |
| Placebo | 2 | 9 | 22.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tamoxifen | 0 of 9 |
| Placebo | 0 of 9 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tamoxifen | 5 of 9 |
| Placebo | 5 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Tamoxifen | Placebo |
|---|---|---|---|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 1 of 9 |
| Bacteremia | Infections and infestations | 0 of 9 | 1 of 9 |
| Arrhythmia | Cardiac disorders | 0 of 9 | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tamoxifen | Placebo |
|---|---|---|---|
| Hot Flashes | General disorders | 3 of 9 | 1 of 9 |
| Night Sweats | General disorders | 1 of 9 | 2 of 9 |
| Mood Alterations | Psychiatric disorders | 1 of 9 | 2 of 9 |
| Nonspecific pain | General disorders | 1 of 9 | 0 of 9 |
| Alteration in smell | General disorders | 0 of 9 | 1 of 9 |
Serious events with the highest arm-level rate: pneumonia (11.1%), bacteremia (11.1%), arrhythmia (11.1%).
The registry lists serious adverse events in the tamoxifen and placebo arms, with 9 participants at risk in each arm. Serious events affected 0 in the tamoxifen arm and 2 in the placebo arm. The record lists no deaths in either arm. These figures are descriptive counts in a small enrolled trial; they do not by themselves establish a difference in safety between the interventions.
The registry also reports 5 participants with other adverse events in each arm, with 9 at risk in each. Serious adverse-event terms listed include pneumonia, bacteremia, and arrhythmia, each shown as 11.1%. The record does not provide event-specific counts in the information available for this summary, nor does it give event timing, severity details beyond the serious-event classification, recurrence, relatedness assessments, or exposure-adjusted rates. The listed percentages should therefore be read as registry entries, not as comparative estimates of risk.
General interpretation of safety data considers the number of participants observed, duration of exposure, event definitions, and completeness of follow-up. A small trial may not characterize uncommon or delayed events precisely. The counts are not sufficient to conclude that one arm is safer or less safe, and zero recorded deaths does not establish absence of other risks. They describe the serious and other adverse-event summaries posted in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase 2 randomized trial of tamoxifen versus placebo in PAH, with an enrollment of 18 and a primary outcome defined as change in TAPSE from Week 0 to Week 24. It also identifies functional, quality-of-life, biomarker, hormone, and echocardiographic assessments. These details explain the trial’s question and measurement framework.
What the record does not provide is the numerical primary-outcome comparison. Arm-specific changes, the between-arm estimate, its uncertainty, and a primary-outcome test result are not reported in the registry record. The listed secondary measures likewise have no numerical findings in the record. As a result, the registry information cannot establish the direction or size of any treatment effect, how precisely it was estimated, or whether a difference would be clinically meaningful.
This absence should not be interpreted as evidence that tamoxifen had no effect, nor as evidence that it had a beneficial or harmful effect. A completed status indicates the trial is marked completed in the registry; it does not substitute for outcome estimates. The posted adverse-event counts describe events recorded in the arms but do not establish comparative safety.
In general, a randomized comparison is most informative when the effect estimate, uncertainty, analysis population, and handling of missing data are available together. Those elements allow readers to distinguish the observed data from conclusions that depend on assumptions. Here, the design and endpoints are described, while primary efficacy results and key analysis details are not reported in the registry record. Any stronger conclusion would go beyond what the posted information supports.
13. Why This Trial Matters Statistically
This trial is statistically notable for the gap between a clearly specified primary measurement and the lack of a posted numerical primary comparison. TAPSE is defined as a continuous echocardiographic measure, with change from Week 0 to Week 24 selected as the primary outcome. The randomized, masked, parallel-arm design sets up a comparative question. Yet design details alone cannot answer that question: readers need the observed changes, a between-arm estimate, and its precision.
The recorded enrollment of 18 also makes transparent uncertainty reporting particularly important. In general, estimates from relatively small studies can be imprecise, although actual precision depends on the observed variability and available data. Enrollment by itself cannot reveal precision, and it should not be treated as a measure of how likely the trial was to detect an effect. The registry’s planning assumptions are described as illustrations based on an observed effect, not as the trial’s own design justification or observed power.
The trial also illustrates why outcome multiplicity and analysis populations matter. Functional measures, quality-of-life measures, biomarkers, hormone levels, and echocardiographic parameters can address different questions. Without a reported analysis plan, multiplicity strategy, missing-data approach, and results, readers cannot tell how those measures were prioritized or how robust any findings might be. The registry record offers a framework for the intended assessment, but not enough numerical evidence to evaluate the primary comparison or secondary findings.
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 principal limitation for interpreting this trial from the registry record is that numerical results for the primary TAPSE outcome are not reported. There are no posted arm-specific mean changes or treatment contrast, and no confidence interval or primary-outcome test result. Results for the listed secondary outcomes are also not reported in the registry record. Consequently, efficacy, precision, and clinical relevance cannot be evaluated from the posted information.
The record does not report outcome-specific participant counts, exclusions, withdrawals, adherence, or the analysis population. It also does not describe the statistical model, baseline adjustment, handling of missing data, or sensitivity analyses. These omissions limit assessment of how the randomized comparison was analyzed and whether incomplete follow-up could affect interpretation.
The registry identifies a primary outcome and multiple secondary assessments, but a multiplicity strategy is not reported. It also does not provide further eligibility details, a placebo administration description beyond “Placebo arm,” or the operational details of masking. The protocol’s sample-size justification, interim analyses, and full statistical plan are not reported in the registry record.
The enrollment of 18 limits the scale of the trial’s recorded experience, but the implications for statistical precision cannot be quantified without outcome variability and estimates. The adverse-event summaries are also limited: exposure duration by participant, event timing, event relatedness, and fuller event-specific detail are not reported. These limitations constrain interpretation of both outcome and safety information without establishing that any particular result is biased or incomplete.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension — NCT03528902.
- Registry record last updated 2024-12-05; status last verified 2024-11.
- Results first posted 2024-12-05.
- 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.
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18. Record Summary
The registry describes a completed phase 2 randomized, quadruple-masked, parallel-arm trial sponsored by Vanderbilt University Medical Center, with enrollment of 18. Tamoxifen was described as 20 mg po TID for 24 weeks; the comparator was a placebo oral tablet. The primary outcome was mean change in TAPSE from Week 0 to Week 24, measured by transthoracic echocardiogram and reported in millimeters.
Secondary outcomes included six-minute walk test distance and quality of life measured with SF36 and emPHasis-10 at baseline and 12 and 24 weeks. The registry reports serious adverse events affecting 0 in the tamoxifen arm and 2 in the placebo arm, with 9 at risk in each arm; other adverse events affected 5 in each arm. No deaths were listed.
Numerical results for the primary and secondary efficacy outcomes, analysis methods, missing-data handling, and analysis populations are not reported in the registry record. The posted information defines the trial question and records selected safety summaries but does not provide the estimates needed to evaluate the primary comparison.