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 Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH (NCT01726049), a randomized phase 3 study. The primary outcome is Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01726049 |
| Phase | Phase 3 |
| Condition | Heart Failure, Diastolic, Pulmonary Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 52 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University Medical Center Groningen |
| Results posted | Yes |
2. Clinical Question
Population
Patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension. The registry describes 52 randomized patients, with 26 assigned to each arm. Mean pulmonary artery pressure change could be evaluated in the registry-labeled intention-to-treat analyses for 21 patients in the sildenafil arm and 22 in the placebo arm.
Intervention
Sildenafil taken orally three times daily: 20 mg for 2 weeks, followed by 60 mg three times daily for 10 weeks.
Comparator
Placebo tablets taken orally. The registry describes three 20 mg tablets, followed by three 60 mg tablets for 10 weeks.
Primary question
How did mean pulmonary artery pressure, measured by right heart catheterization, change between baseline and 12 weeks in each randomized arm? The study summary also describes interest in cardiac output and exercise capacity, but the posted primary result concerns mean pulmonary artery pressure. The registry does not post a usable two-arm comparison for this continuous primary outcome, so the arm-specific estimates alone do not establish the treatment contrast.
3. Trial Design
This was a phase 3, randomized, quadruple-masked, parallel-group trial sponsored by University Medical Center Groningen. The registry lists heart failure, diastolic, and pulmonary hypertension as conditions. The study is marked completed. Its recorded start was 2011-10, and its primary completion was 2014-09.
The registry records 52 participants randomized, with 26 in the sildenafil arm and 26 in the placebo arm. The sildenafil regimen was oral dosing three times daily, with 20 mg for 2 weeks followed by 60 mg for 10 weeks. The placebo arm is described as placebo tablets taken orally, with three 20 mg tablets followed by three 60 mg tablets for 10 weeks. Further details about how masking was maintained or how treatment adherence was assessed are not reported in the registry record.
The primary outcome was mean pulmonary artery pressure measured invasively by right heart catheterization. It concerns change from baseline to 12 weeks. The registry also lists VO2max, cardiac output measured invasively by right heart catheterization, and wedge pressure measured invasively by right heart catheterization as secondary outcomes. The record lists five outcome measures and eight analyses, but does not describe the full set of analysis methods or how each analysis relates to the outcomes.
The primary outcome description says that change could be evaluated in the registry-labeled intention-to-treat analyses for 21 patients in the sildenafil arm and 22 in the placebo arm. The reasons that measurements were unavailable for other randomized participants, and the handling of missing outcomes, 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
| Stage | Sildenafil | Placebo |
|---|---|---|
| STARTED | 26 | 26 |
| COMPLETED | 21 | 22 |
| NOT COMPLETED | 5 | 4 |
Reasons for not completing this period:
| Reason | Sildenafil | Placebo |
|---|---|---|
| Death | 1 | 1 |
| Adverse Event | 4 | 1 |
| refused second HC | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: 52 patients randomized. 26 Sildenafil arm: 26 placebo arm: change in mean pulmonary artery pressure could be evaluated in the intention to treat (ITT) analyses in 21 and 22 subjects of the Sildenafil and placebo treatment group
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 | Sildenafil | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 26 | 26 | 52 | |
| Age, Continuous | years | 72 (SD 12) | 76 (SD 7) | 74 (SD 10) |
| Sex: Female, Male: Female | Participants | 20 | 17 | 37 |
| Sex: Female, Male: Male | Participants | 6 | 9 | 15 |
| Region of Enrollment: Netherlands | participants | 26 | 26 | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization, measured over baseline and 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mmHG |
| Endpoint classification | Continuous Endpoint |
Mean pulmonary artery pressure is a measure of pressure in the pulmonary artery. In this trial it was measured by right heart catheterization, an invasive measurement method, at baseline and 12 weeks. The primary endpoint is the change between those time points, expressed in mmHG. The posted arm estimates are means, with 95% confidence intervals.
Measuring change allows the outcome to be expressed in relation to each participant’s baseline measurement rather than as a follow-up value alone. Comparing changes between randomized groups can address whether the groups followed different average trajectories over the study period. That comparison needs a between-group estimate and its uncertainty; arm-specific changes do not by themselves provide that contrast. Such a two-arm estimate is not reported in the registry record.
General: Pulmonary artery pressure is relevant to the study’s stated question about pulmonary hypertension in HFpEF. It is one physiological measure, not a complete description of symptoms, exercise capacity, cardiac output, or overall health. The registry summary also mentions the aim of assessing cardiac output and exercise capacity, but the posted primary endpoint is pressure change. A result for that endpoint should therefore be interpreted as evidence about the measured pressure outcome, not as a substitute for findings on the other outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted arm-level mean change in mean pulmonary artery pressure was -2.4 mmHG in the sildenafil group, with a 95% confidence interval from -4.5 to -0.3. In the placebo group, the reported mean change was -4.7 mmHG, with a 95% confidence interval from -7.1 to -2.3. These are within-arm estimates. The registry record does not report a two-arm contrast, confidence interval for the contrast, or p-value for the primary outcome.
Both reported means are negative. The registry describes the endpoint as change between baseline and 12 weeks but does not state the subtraction convention used to define change. The sign should therefore be read as the recorded direction of change, rather than assigned a clinical direction without that detail. The confidence intervals indicate uncertainty around each arm’s mean estimate under the analysis used. They do not give the uncertainty around the difference between arms.
The arm-specific intervals do not replace a formal comparison. A treatment contrast requires an estimate of how the groups differ, with its own uncertainty and an analysis that accounts for the study design. The registry does not post those comparative statistics for this continuous endpoint. It is therefore not possible from these entries to determine the precision of the between-arm effect or to make a formal statistical conclusion about the primary comparison.
The registry states that outcome change could be evaluated in the intention-to-treat analyses for 21 sildenafil participants and 22 placebo participants, although 26 were randomized to each arm. The record does not explain why the outcome was unavailable for some randomized participants, or describe how missingness was handled. That information matters because an arm-specific estimate based on observed measurements can be affected by which participants contributed data.
The results should also be kept within the scope of the endpoint. The primary outcome is mean pulmonary artery pressure measured by catheterization at baseline and 12 weeks. The registry lists VO2max, cardiac output, and wedge pressure as secondary outcomes, but does not report their numerical results in the registry record for this analysis. The posted primary estimates do not establish findings for those outcomes, nor do they establish effects on broader clinical outcomes.
9. Statistical Methods Explained
General: A mean summarizes the central value of a continuous measurement. Here, the registry reports mean changes in mean pulmonary artery pressure for each arm. A mean is useful for describing the average recorded change, but it does not show the full distribution of individual changes. The spread of individual results, including whether some participants changed in a different direction from the average, is not reported in the registry record.
What does a 95% confidence interval describe?
General: A confidence interval communicates uncertainty in an estimated quantity. Its width reflects the precision of the estimate under the assumptions of the analysis: a narrower interval generally indicates greater precision, while a wider interval indicates less precision. The intervals posted accompany each arm’s mean change. They are not confidence intervals for the difference between sildenafil and placebo. Their interpretation also depends on the statistical method used to construct them, which is not reported in the registry record.
The registry reports the sildenafil mean change as -2.4 mmHG, with a 95% confidence interval from -4.5 to -0.3, and the placebo mean change as -4.7 mmHG, with a 95% confidence interval from -7.1 to -2.3. Those values describe estimates within each arm. They do not show the estimated between-arm difference, the precision of that difference, or a test of the primary comparison. The registry does not report a p-value for these arm-level entries.
Why is the between-arm estimate important?
General: In a randomized parallel-group trial, the main comparative question is ordinarily addressed by estimating how outcomes differ between the assigned groups. For a change endpoint, an analysis might compare the groups’ mean changes or use another prespecified method to account for baseline and follow-up measurements. Different methods can produce different estimates and uncertainty, so the chosen approach matters. The registry does not report the method used for the primary analysis or a comparative estimate for this outcome. A contrast cannot be reconstructed from the posted arm means and confidence intervals alone without additional assumptions.
The endpoint is described as change between baseline and 12 weeks, but the precise change calculation and the confidence-interval method are not reported in the registry record. Nor does the record say whether the primary analysis adjusted for other variables. These omissions limit how fully the statistical result can be assessed.
What does randomization contribute?
General: Random assignment is intended to make the groups comparable, on average, with respect to factors known and unknown at the time of assignment. It supports a causal comparison when the analysis retains the randomized groups and missing outcome data and other departures are handled appropriately. Randomization does not guarantee identical groups in a trial, and it does not by itself resolve missing-data concerns. The registry reports randomized assignment but does not describe sequence generation, allocation concealment, or the analysis details needed to assess how the randomized comparison was implemented.
The record identifies the trial as quadruple-masked. This indicates the recorded masking category, but the registry does not specify which roles were masked, how masking was maintained, or whether masking was assessed. Those operational details are not reported in the registry record.
How should planning calculations be read?
General: Sample-size calculations are planning tools. A calculation based on an observed effect is an illustration of the sample size that might be needed under stated assumptions; it is not evidence that a completed trial had adequate power, and it is not observed power. The stated planning assumptions for illustrations in this analysis are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. The registry’s own design assumptions and sample-size justification are not reported in the registry record. Such planning illustrations should not be confused with the enrollment or the number of outcome measurements available for analysis.
General: Multiplicity arises when several outcomes, time points, or analyses are considered. The chance of at least one apparently unusual result can increase when many tests are conducted without accounting for that broader testing. The record lists five outcome measures and eight analyses, and identifies three posted secondary outcomes. A multiplicity strategy, such as a testing hierarchy or adjustment, is not reported in the registry record. It is therefore not possible to determine from the record whether or how the analyses were adjusted for multiple testing.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Mean Difference (Final Values) -2.4 | -4.5 to -0.3 | not reported |
| not stated | Mean Difference (Final Values) -4.7 | -7.1 to -2.3 | not reported |
The registry posts arm-specific analyses for mean change in the primary outcome: -2.4 mmHG for sildenafil, with a 95% confidence interval from -4.5 to -0.3, and -4.7 mmHG for placebo, with a 95% confidence interval from -7.1 to -2.3. The analysis entries label these as mean differences in final values, while the primary outcome description calls the measure change between baseline and 12 weeks. The registry does not give further detail reconciling those descriptions.
No sponsor-reported two-arm estimate, confidence interval for a contrast, or p-value is posted for this continuous outcome. A simple unadjusted recalculation of a two-arm contrast is not available from the posted summary statistics as represented in the registry record. The relevant comparison is therefore not estimable from these entries, and there is no recalculated comparative result to set against the sponsor’s analysis. The record does not flag a discrepancy between sponsor results and recalculation.
For interpretation, the posted sponsor analysis remains the source for the arm-level values, but those values should not be treated as the randomized between-arm effect. The method used for the sponsor’s analysis and details of any adjusted or otherwise prespecified comparative analysis are not reported in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and eight analyses, and identifies VO2max, invasively measured cardiac output, and invasively measured wedge pressure as secondary outcomes. The primary outcome is mean pulmonary artery pressure measured by right heart catheterization. The registry record does not describe a prespecified hierarchy among outcomes, a family of primary comparisons, an adjustment for multiple testing, or a plan for interpreting multiple analyses. Without that information, the extent to which multiplicity was considered is not reported in the registry record.
Missing outcome information is also relevant. Although 26 patients were randomized to each arm, the primary outcome description says change could be evaluated in the registry-labeled intention-to-treat analyses for 21 sildenafil patients and 22 placebo patients. The registry does not report why measurements were not evaluable for all randomized participants. It does not specify whether missing measurements were imputed, whether a particular missing-data assumption was used, or whether sensitivity analyses were conducted. The missing-data mechanism and its possible effect on the estimates are therefore unknown from the registry record.
The term intention-to-treat appears in the primary outcome description, but the record does not provide enough detail to assess how the analysis population was defined or whether every randomized participant was included in the analysis. It also does not report a protocol-defined analysis plan, interim analyses, or a sample-size justification. These details should not be inferred from the completed status or the posted arm-level results.
In general, multiplicity and missing-data methods affect how uncertainty and evidence are interpreted. They do not change the descriptive fact that the registry posts arm-level mean changes with confidence intervals. They do limit what can be concluded about a comparative treatment effect from those entries.
12. 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 |
|---|---|---|---|
| Sildenafil | 4 | 26 | 15.4% |
| Placebo | 3 | 26 | 11.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sildenafil | 22 of 26 |
| Placebo | 21 of 26 |
Most frequent serious adverse event terms
| Event term | Organ system | Sildenafil | Placebo |
|---|---|---|---|
| pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 26 | 2 of 26 |
| intestinal infarction | Gastrointestinal disorders | 0 of 26 | 1 of 26 |
| cardiac failure | Cardiac disorders | 1 of 26 | 0 of 26 |
| pseudoaneurysma | Vascular disorders | 1 of 26 | 0 of 26 |
| medical device complication | Vascular disorders | 1 of 26 | 0 of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sildenafil | Placebo |
|---|---|---|---|
| respiratory tract infection | Infections and infestations | 9 of 26 | 3 of 26 |
| myalgia | Musculoskeletal and connective tissue disorders | 4 of 26 | 4 of 26 |
| headache | General disorders | 4 of 26 | 3 of 26 |
| visual impairment | Eye disorders | 0 of 26 | 5 of 26 |
| nausea | Gastrointestinal disorders | 2 of 26 | 2 of 26 |
| dizziness | Nervous system disorders | 1 of 26 | 3 of 26 |
| chest pain | Respiratory, thoracic and mediastinal disorders | 2 of 26 | 1 of 26 |
Serious events with the highest arm-level rate: pneumonia (7.7%), intestinal infarction (3.8%), cardiac failure (3.8%), pseudoaneurysma (3.8%), medical device complication (3.8%).
The registry reports serious adverse events for 4 of 26 participants at risk in the sildenafil group and 3 of 26 at risk in the placebo group. It also reports other adverse events for 22 of 26 participants at risk in the sildenafil group and 21 of 26 at risk in the placebo group. These are counts of participants recorded as affected, not estimates of the comparative risk adjusted for follow-up or other factors.
The registry lists pneumonia at 7.7% and intestinal infarction, cardiac failure, pseudoaneurysma, and medical device complication at 3.8% each among the top serious adverse event terms. The record does not specify the denominator or additional coding details for those term percentages, so they should be read as reported rather than independently interpreted as rates in a defined population. Death counts are not reported in the registry record.
These safety entries are descriptive. They do not establish whether an event was caused by a study drug, and the registry record does not report a causal attribution method, severity grading details, or a comparative statistical analysis of adverse events. Counts from a trial of this size should not be treated as definitive evidence of a difference in safety. The posted figures describe what the registry records; they do not, on their own, determine the clinical significance of the events.
13. What the Result Does, and Does Not, Mean
The registry records a randomized, quadruple-masked comparison of sildenafil and placebo in patients with HFpEF and pulmonary hypertension. The primary outcome was mean pulmonary artery pressure measured by right heart catheterization, with change assessed between baseline and 12 weeks. The posted arm-level mean changes were -2.4 mmHG for sildenafil and -4.7 mmHG for placebo, each accompanied by a 95% confidence interval.
Those estimates describe the reported mean change in each arm. The registry does not provide a comparative estimate for the primary outcome, a confidence interval for the difference between arms, or a p-value. Consequently, the posted entries do not establish the size or precision of a randomized between-arm effect. The sign convention for change is also not described, which limits interpretation of the direction of the negative values.
The primary result does not answer every question stated in the study summary. The summary mentions cardiac output and exercise capacity, while the registry lists VO2max, cardiac output, and wedge pressure as secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record. The primary endpoint alone cannot establish findings for these other measures.
Nor do the posted primary results establish a broader clinical benefit or harm. Mean pulmonary artery pressure is a measured physiological outcome; it is not, by itself, a measure of all symptoms, functional ability, or clinical events. The adverse-event counts provide descriptive safety information, but do not establish causation or a statistically assessed safety difference.
In general, a randomized comparison is most informative when the between-group estimate, its uncertainty, the analysis population, and the handling of missing outcomes are clear. Here, the registry provides arm-level estimates and partial information about outcome availability, but does not report several of those comparative and methodological details. Conclusions should remain limited to the record’s reported measurements and their stated uncertainty.
14. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between describing each randomized arm and estimating the contrast that answers a comparative question. The registry reports a mean change and confidence interval for each arm, but does not report the between-arm estimate for the continuous primary endpoint. Readers can identify the posted arm-level summaries, yet those summaries are not a substitute for the randomized treatment contrast.
The record also makes outcome availability visible. It reports 26 randomized participants in each arm, while the primary outcome description identifies 21 and 22 participants as evaluable in the corresponding analyses. This difference between randomized and evaluable participants matters when assessing analysis populations and possible missing-data effects. The reasons for unavailable measurements and the handling of missing data are not reported in the registry record.
The study further illustrates why uncertainty needs to be attached to the right quantity. The posted 95% confidence intervals quantify uncertainty around arm-level means; they do not quantify uncertainty around the difference between arms. A statistically sound interpretation depends on the estimand and analysis being reported, not simply on the presence of intervals beside each group estimate.
Finally, the registry lists multiple outcome measures and analyses but does not report a multiplicity plan. This does not invalidate the descriptive results, but it leaves unanswered how the collection of analyses was intended to inform confirmatory conclusions. Together, these features make the record a practical example of how completeness of comparative reporting, missing-data documentation, and analysis planning affects statistical interpretation.
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.
Several trial-specific details needed for a full statistical appraisal are not reported in the registry record. The primary outcome is described as change between baseline and 12 weeks, but the sign convention and the detailed calculation of change are not stated. The registry does not describe the method used to construct the arm-level confidence intervals, nor does it post a between-arm estimate or a p-value for the continuous primary endpoint.
The primary outcome description gives the number of participants whose change could be evaluated in the registry-labeled intention-to-treat analyses, but does not explain why outcome measurements were unavailable for some randomized participants. It also does not describe the missing-data method, the exact analysis population, or sensitivity analyses. These omissions limit assessment of how representative the analyzed measurements are of the randomized groups.
The registry identifies the study as quadruple-masked, but does not report which trial roles were masked or how masking was implemented. Details of random sequence generation and allocation concealment are not reported in the registry record. The protocol, statistical analysis plan, interim analyses, and sample-size justification are also not reported, so they cannot be used to determine whether the posted analyses follow prespecified methods.
The record lists multiple outcomes and analyses but does not describe how multiplicity was handled. It lists three secondary outcomes, but numerical results for those outcomes are not reported in the registry record. The safety entries do not include reported death counts, detailed event-attribution methods, or a comparative safety analysis. These limitations concern reporting and interpretation; they do not establish that particular methods were or were not used outside the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH — NCT01726049.
- Registry record last updated 2016-03-21; status last verified 2016-02.
- Results first posted 2016-03-21.
- 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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19. Record Summary
NCT01726049 is a completed phase 3, randomized, quadruple-masked, parallel-group trial sponsored by University Medical Center Groningen. It enrolled 52 patients with HFpEF and pulmonary hypertension, with 26 assigned to sildenafil and 26 to placebo. The recorded study start was 2011-10 and primary completion was 2014-09.
The primary outcome was change in mean pulmonary artery pressure measured by right heart catheterization between baseline and 12 weeks. The registry reports arm-level mean changes and 95% confidence intervals, but not a two-arm comparison for this continuous outcome. The outcome was evaluable in the registry-labeled intention-to-treat analyses for 21 sildenafil participants and 22 placebo participants. Reasons for missing measurements and their handling are not reported in the registry record.
VO2max, cardiac output, and wedge pressure are listed as secondary outcomes. The registry also records adverse-event counts by arm. A full statistical analysis plan, multiplicity strategy, and sample-size justification are not reported in the registry record.