Effects of Oral Sildenafil on Mortality in Adults With PAH: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Oral Sildenafil on Mortality in Adults With PAH (NCT02060487), a randomized phase 4 study. The primary outcome is Overall Survival.

2. Clinical Question

The trial was designed to assess relative effects on mortality among adults with PAH receiving sildenafil at three doses. The posted primary outcome counts deaths from the first day of study treatment through the date of death, within a maximum duration of 2102 days. The registry record identifies the primary analysis population as participants who were randomized and treated with study treatment.

The central dose comparisons are the 20 mg and 80 mg groups against the 5 mg group. These are comparisons among three sildenafil doses, not a comparison with placebo or with no treatment. The registry record also lists a hazard-ratio analysis directly comparing the 20 mg and 80 mg arms.

Clinical worsening and 6-minute walk distance were additional questions. The registry record lists clinical worsening events and changes from baseline in 6-minute walk distance at Month 6 and Month 12. The number of posted secondary outcomes is three, while the number of outcome measures is four. The exact statistical question for each outcome is limited to what is described in the registry record; further endpoint definitions or hypotheses are not reported in the registry record.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 4 study. The registry record lists 385 participants enrolled and describes the study as multinational and multicenter. Participants were assigned to one of three sildenafil dose groups: 5 mg, 20 mg, or 80 mg. The brief study description states that each dose was administered three times per day. Arm descriptions beyond the dose labels are not reported in the registry record.

The trial began on 2014-09-22, and the primary completion date is listed as 2021-02-26. Its status is terminated. The registry record does not state why the study was terminated, so the status alone does not establish the reason or its implications for the results.

The primary outcome was overall survival, expressed as the number of participants who died during the study. The outcome timeframe begins on Day 1 of study treatment and extends to death, within a maximum duration of 2102 days. The primary population is described as the intent-to-treat population, defined in the registry record as all randomized participants treated with study treatment.

The record lists three secondary outcomes: participants with clinical worsening events and change from baseline in 6-minute walk distance at Month 6 and Month 12. The clinical-worsening timeframe is Day 1 of study treatment through the event, within a maximum duration of 2080 days. Further details about how the 6-minute walk outcomes were analyzed are not reported in the registry record. The original sample-size justification, allocation ratio, trial-specific statistical plan, interim analyses, and reasons for termination 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat population (ITT) included all randomized participants treated with study 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: All randomized participants were included in the baseline analysis population.

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival, measured over Day 1 of study treatment up to date of death (within a maximum duration of 2102 days).

Overall survival is the primary endpoint. In this record it is measured as a count of participants who died during the study, from Day 1 of study treatment through the date of death, within a maximum duration of 2102 days. The reported counts are 34 participants in the 5 mg group, 25 in the 20 mg group, and 19 in the 80 mg group. The analysis population is described as the intent-to-treat population: all randomized participants treated with study treatment.

Survival is used to capture deaths over the study period rather than a change in a symptom score or functional measure. In general, an endpoint based on death is clinically direct, but interpreting group differences still depends on the analysis method, follow-up, and uncertainty around the estimates. The registry record reports both death counts and hazard-ratio analyses; the posted re-calculations also express the comparisons as risk differences using the counts and group sizes.

The endpoint description does not give additional detail about causes of death, adjudication procedures, or how participants without a recorded death were handled in the time-to-event analyses. Those details are not reported in the registry record. The maximum follow-up duration is not a statement that every participant was followed for that length of time.

7. Results Posted in the Registry

• Sildenafil 20 mg: 19.5% (25/128) versus 26.4% (34/129) on control; risk difference -6.8 percentage points (95% CI -17.1 to 3.4), risk ratio 0.74 (0.47–1.17); unadjusted two-proportion z-test p = 0.193.
• Sildenafil 80 mg: 14.8% (19/128) versus 26.4% (34/129) on control; risk difference -11.5 percentage points (95% CI -21.3 to -1.7), risk ratio 0.56 (0.34–0.93); unadjusted two-proportion z-test p = 0.023.

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.

Number of Participants With Clinical Worsening Events

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Sildenafil 20 mg: 28.1% (36/128) versus 40.3% (52/129) on control; risk difference -12.2 percentage points (95% CI -23.7 to -0.7), risk ratio 0.70 (0.49–0.99); unadjusted two-proportion z-test p = 0.040.
  • Sildenafil 80 mg: 21.9% (28/128) versus 40.3% (52/129) on control; risk difference -18.4 percentage points (95% CI -29.5 to -7.3), risk ratio 0.54 (0.37–0.80); unadjusted two-proportion z-test p = 0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Sildenafil 20 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Sildenafil 80 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover clinical worsening events and changes from baseline in 6-minute walk distance at Month 6 and Month 12. The posted clinical-worsening results show fewer participants with events in the higher-dose groups than in the 5 mg group. The record also includes hazard-ratio analyses for clinical worsening, with Wald tests. Numerical interpretation of each endpoint belongs with its individual results rather than being repeated as a combined claim.

Across the posted outcomes, the direction of the clinical-worsening comparisons is broadly consistent with the direction of the observed death counts: the higher-dose groups have fewer recorded events than the 5 mg group. This directional pattern does not make the endpoints interchangeable. Death and clinical worsening represent different outcomes, and the secondary findings do not independently establish what happened to overall survival.

The registry lists the two 6-minute walk distance timepoints, but further details of their posted results and analyses are not reported in the registry record. Therefore, no conclusion about the pattern of those functional outcomes can be drawn from the endpoint titles alone.

Unadjusted secondary results carry less weight as confirmatory evidence because several outcomes and comparisons are considered, and the registry record does not report a multiplicity strategy. When multiple tests are performed, the chance of at least one apparently notable result can increase. General explanation: adjustment or a prespecified hierarchy can address this issue, but the method and plan must be known to interpret the results accordingly. The reported secondary p-values are unadjusted, so they should be read as exploratory evidence rather than as a substitute for the primary endpoint analysis.

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

• Number of Participants With Clinical Worsening Events
• Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 6
• Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 12

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical summaries appear in the registry record and in the unadjusted re-calculations. They describe different aspects of the data, so each should be read according to the question it answers. Details of the trial’s original statistical plan, including the prespecified methods for the primary endpoint, are not reported in the registry record.

What does a risk difference describe?

General explanation: a risk difference subtracts the event proportion in one group from the event proportion in a reference group. A negative value in these comparisons means the observed proportion with the event was lower in the named dose group than in the 5 mg group. The primary re-calculated risk differences are -0.068 for 20 mg versus 5 mg and -0.115 for 80 mg versus 5 mg. The corresponding intervals describe uncertainty around those estimates. These are simple unadjusted re-calculations from posted summary statistics, rather than the registry-reported hazard-ratio analyses.

A risk difference is an absolute comparison, not a relative one. It can be easier to connect to the observed difference in event proportions, but it does not account for when events occurred or for differing follow-up time in the way a time-to-event analysis can. The registry record gives a maximum duration for the primary outcome, but does not provide all participant-level timing or censoring information in the summary results.

How does a hazard ratio differ?

General explanation: a hazard ratio compares the relative event rate over time between groups, subject to the assumptions of the chosen time-to-event model. A hazard ratio of 1 represents equal hazards under that model; a value below 1 indicates a lower estimated hazard in the numerator group relative to the denominator group, depending on the order of groups in the analysis. The registry record reports hazard ratios for three pairwise group combinations, but it does not identify the order convention, analysis method, or model details for the primary endpoint. The hazard-ratio confidence intervals therefore need to be interpreted as registry-reported estimates, without assuming unreported model specifications.

A hazard ratio and a risk difference cannot be read as the same quantity. The former uses event timing, while the latter compares the observed proportions with an event. In this trial, the primary re-calculation and the registry-reported hazard-ratio analyses are complementary descriptions, not duplicate calculations. They can differ in estimate and uncertainty because they use different statistical summaries.

What do confidence intervals and p-values add?

General explanation: a confidence interval gives a range of values compatible with the data and the method used, at the stated confidence level. It communicates precision as well as direction. For a risk difference, an interval that includes zero is compatible with no difference under that calculation. For a hazard ratio, the corresponding reference value is 1. A p-value measures how unusual data at least as extreme as those observed would be under a specified null model; it does not give the probability that the null hypothesis is true, nor does it measure clinical importance.

The posted re-calculation p-values are unadjusted. They do not account for the number of outcomes or comparisons. The primary registry hazard-ratio entries do not include p-values, and the reported confidence intervals are 99.7%. The registry record labels these analyses as non-inferiority, but does not report the non-inferiority margin or further details needed to assess that framework. The absence of a p-value should not be filled in by inference from a separate calculation.

Why does over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It can lead to confidence intervals that are too narrow and tests that appear more decisive if the extra variability is ignored. This concept is relevant to some count-data analyses, but the primary endpoint is reported as participants with an event, and the registry record does not identify an over-dispersion model for the primary analysis. Whether such a model was used is not reported in the registry record; no conclusion about over-dispersion should be inferred from the outcome being a count of participants.

What remains unspecified?

The original analysis plan, covariate adjustment, handling of missing data, censoring rules, interim analyses, and multiplicity strategy are not reported in the registry record. The methods behind the primary hazard-ratio analyses are also not reported there. For clinical worsening, the registry record reports Wald tests for the hazard-ratio analyses, but does not provide the full model specification. Without these details, the results can be described as posted, but not reconstructed as a complete trial analysis plan.

General explanation: statistical methods are most interpretable when the estimand, population, endpoint, follow-up, comparison, and analysis method are all clearly specified. A registry summary may not contain every operational detail. For this trial, the population description and outcome timeframes are available, while important analysis and missing-data details are not reported in the registry record. That uncertainty in documentation limits how far the posted summaries can be independently evaluated.

11. Confidence Intervals and Precision

Precision is conveyed most directly by the width of a confidence interval: a narrower interval indicates less uncertainty under the method used, while a wider interval indicates more. General explanation: the interval does not guarantee that the true value lies within its limits, and its coverage interpretation depends on the statistical method and assumptions. It is not a range containing a stated proportion of individual participant outcomes.

For the re-calculated primary risk difference between 20 mg and 5 mg, the estimate is -0.068 and the 95% confidence interval is -0.171 to 0.034. Because the interval includes zero, the posted summary statistics are compatible with a range of differences that includes no difference. For 80 mg versus 5 mg, the estimate is -0.115 and the 95% confidence interval is -0.213 to -0.017. That interval lies below zero, but still allows a range of possible magnitudes.

The registry-reported primary hazard-ratio intervals are 99.7% intervals and are wide: 0.31 to 1.49 for 5 mg versus 20 mg, 0.22 to 1.21 for 5 mg versus 80 mg, and 0.30 to 1.84 for 20 mg versus 80 mg. Each includes 1, the reference value for equal hazards. These intervals differ in confidence level and estimand from the 95% risk-difference intervals, so their widths should not be compared as if they were the same analysis.

The reported counts and group sizes are limited in scale, and the intervals reflect uncertainty in the estimates. The registry record does not provide additional information about the primary analysis method or adjustment that would support a more detailed precision assessment. Confidence intervals communicate statistical uncertainty, not the probability that a result is clinically important.

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 figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. For these binary outcomes, the entries are participants per arm, not total event counts. The planning assumptions listed are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm under which a study would have an 80% chance of detecting the specified effect if that effect were the true one and the stated assumptions held. The 90% power column gives the corresponding number of participants per arm for a higher chance of detection under those same assumptions. These are planning concepts, not guarantees of what a future study would find.

Rows planning for 100%, 75%, or 50% of the observed effect ask what sample size would be needed to detect the observed effect or a smaller fraction of it. Smaller effects generally require more participants to distinguish them from random variation. Accordingly, the illustrated sample sizes increase as the assumed detectable effect becomes smaller.

These figures are planning illustrations, not observed power. They do not describe the probability that the completed trial’s findings are true, and they are not a retrospective measure of whether the study succeeded. The accompanying curve should be read as illustrating the planning relationship between assumed effect size and sample size, rather than as additional trial outcome evidence.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.264; treatment proportion p₁ = 0.195; average p̄ = 0.229.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5946 = 1.1655.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5927 = 0.4988.
4. n = (1.1655 + 0.4988)² / (-0.0683)² = 594.6, rounded up to 595 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
p0 <- 0.263565891472868                          # control proportion
p1 <- 0.1953125                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2060487)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 595 (80% power), 796 (90% power)
 75% of observed effect: n per arm = 1,086 (80% power), 1,453 (90% power)
 50% of observed effect: n per arm = 2,503 (80% power), 3,350 (90% power)
power.prop.test: 594.6 
Simulated power at n = 595 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 registry record reports primary hazard-ratio analyses labeled non-inferiority. Those analyses are distinct from the posted re-calculations, which compare event proportions as unadjusted risk differences using the group counts and sizes. The registry-reported hazard ratios are 0.68 for 5 mg and 20 mg, 0.51 for 5 mg and 80 mg, and 0.74 for 20 mg and 80 mg, each with a 99.7% confidence interval. The primary entries do not include p-values.

The re-calculated risk differences use a different summary measure and have 95% confidence intervals and unadjusted p-values. Because the measures and approaches differ, they should not be treated as competing estimates of exactly the same quantity. The re-calculation does not supersede the registry analysis. No discrepancy is flagged between the posted summaries and re-calculations.

The registry record does not report the method or model details for the primary hazard-ratio analyses, or the non-inferiority margin. The non-inferiority labels therefore describe how the analyses are classified in the record, but the information needed to evaluate the design and decision rule is not reported in the registry record. The registry-reported analysis remains the trial’s posted analysis; the unadjusted calculations offer a separate descriptive view of the posted counts.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and several secondary outcomes, along with pairwise comparisons among dose groups. It does not report how the trial handled multiplicity: whether any outcomes or comparisons were designated as confirmatory, whether testing followed a hierarchy, or whether p-values were adjusted. This matters because evaluating multiple outcomes and group comparisons can increase the chance of observing a nominally notable result by chance. The posted re-calculation p-values are unadjusted.

The primary hazard-ratio analyses are labeled non-inferiority, but the non-inferiority margin, decision rule, and detailed analysis plan are not reported in the registry record. Without the margin and method, the label alone is not enough to determine whether the statistical criterion for non-inferiority was satisfied. The primary hazard-ratio p-values are also not reported.

The primary population is described as the intent-to-treat population, defined as all randomized participants treated with study treatment. The record does not describe how missing outcome information was handled, whether all participants contributed to each analysis, or how censoring was handled in the time-to-event analyses. These details are not reported in the registry record and should not be inferred from the group sizes or outcome counts.

Interim analyses and any related stopping rules are not reported in the registry record. Nor are the original statistical analysis plan, covariate adjustments, or full model specifications for the primary analysis. The trial status is terminated, but the reason for termination and its relationship, if any, to analyses or interim monitoring are not reported in the registry record. These omissions limit independent assessment of the confirmatory framework and the potential influence of missing information or multiple testing.

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: pulmonary arterial hypertension (13.2%), right ventricular failure (8.5%), cardiac failure (7.0%), pneumonia (5.4%), dyspnoea (3.1%).

The adverse-event summary reports serious adverse events in 66 of 129 participants in the 5 mg group, 49 of 128 in the 20 mg group, and 51 of 128 in the 80 mg group. The group summaries also report other adverse events in 108 of 129, 107 of 128, and 111 of 128 participants, respectively. These are descriptive participant counts in the registry record; they do not by themselves establish a causal relation to study treatment.

The most frequent serious adverse-event terms listed are pulmonary arterial hypertension (13.2%), right ventricular failure (8.5%), cardiac failure (7.0%), pneumonia (5.4%), dyspnoea (3.1%), and pulmonary hypertension (3.1%). The record does not provide further information in this summary about event severity gradations, attribution, timing, or whether an individual participant could contribute to more than one term.

Death counts are also reported by dose group as part of the primary outcome. Safety counts and mortality analyses are related aspects of the trial record but are not interchangeable: serious adverse events describe a safety category, while overall survival counts deaths over the specified follow-up. The registry record alone does not support a broader safety comparison beyond the posted information.

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

The results describe the outcomes recorded among participants assigned to three sildenafil doses in this randomized study. The primary endpoint counts deaths during study follow-up. The observed counts were 34 in the 5 mg group, 25 in the 20 mg group, and 19 in the 80 mg group. The unadjusted re-calculations show risk differences below zero for both higher-dose comparisons, but their uncertainty differs: the 20 mg interval includes zero, while the 80 mg interval does not.

The registry-reported primary hazard-ratio analyses give a separate time-to-event perspective. Their 99.7% confidence intervals include 1 for all three pairwise comparisons. The record labels these analyses non-inferiority, but does not report the margin or details needed to assess the non-inferiority decision. The re-calculated risk differences and registry hazard ratios therefore should not be collapsed into a single conclusion.

These findings do not establish why the observed group differences occurred, whether they would be reproduced in another study, or how results would compare with treatments or populations not included in this trial. The registry record compares sildenafil doses and contains no placebo or untreated comparison group. The secondary outcomes and adverse-event summaries add context, but do not change the distinction between the trial’s primary endpoint and its other measures.

Statistical significance is not the same as clinical importance, and a confidence interval is not a guarantee about the true effect. The termination status also does not explain why the study ended; the reason is not reported in the registry record. The results should be understood as estimates from this trial with the analysis and reporting limitations described, not as medical advice or a treatment recommendation.

18. Why This Trial Matters Statistically

This study is statistically informative because it places three dose groups within a randomized, parallel-group comparison and reports both death counts and time-to-event hazard ratios. Randomization can support comparisons between assigned groups, but interpretation still depends on follow-up, endpoint definitions, analysis methods, and uncertainty. The registry record identifies the study as quadruple-masked and describes the primary population and outcome timeframe.

The results illustrate why statistical summaries need to be distinguished. A risk difference expresses an absolute difference in observed event proportions, while a hazard ratio describes a relative comparison over time. The posted re-calculation and registry-reported analysis do not answer precisely the same statistical question. Reading both alongside their confidence intervals gives a fuller account than relying on a single point estimate.

The record also illustrates the importance of prespecification and reporting. Although the primary analyses are labeled non-inferiority, the margin and analysis details are not reported. Multiplicity handling, missing-data methods, interim analyses, and the original sample-size justification are also not reported in the registry record. These gaps limit evaluation of how the analyses were planned and how strongly the results should be treated as confirmatory.

Finally, the secondary clinical-worsening results and the safety summaries show why evidence across endpoints must be interpreted carefully. Similar directions across outcomes can be relevant context, but secondary results without a reported multiplicity strategy carry less confirmatory weight. The registry record offers useful outcome summaries while leaving important design and analysis details unresolved.

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.

Several limitations are specific to the information reported for this trial. The status is terminated, but the reason for termination is not reported in the registry record. The record gives enrollment and outcome counts, but does not explain whether termination affected follow-up, planned recruitment, or analysis. Those implications cannot be inferred from status alone.

The registry-reported primary hazard-ratio analyses are labeled non-inferiority, yet the non-inferiority margin, model, group-order convention, and other analytic details are not reported. The primary hazard-ratio entries also do not include p-values. The unadjusted re-calculations use posted counts and group sizes and are not substitutes for the original time-to-event analysis.

The registry record does not report the original sample-size justification, missing-data procedures, censoring rules, interim analyses, or multiplicity plan. The analysis population is described as randomized participants treated with study treatment, but there is no additional detail about how the analysis set was assembled or how incomplete outcome information was handled. These gaps constrain independent assessment of precision and potential bias.

The arm descriptions provide dose labels, while other details of treatment delivery or participant characteristics are not reported in the registry record. The summary also does not provide further information about the 6-minute walk distance results or their statistical methods. Finally, the trial compares three sildenafil doses, so its results do not supply a comparison with placebo or no treatment. These limitations define what can be concluded from the registry summaries.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effects of Oral Sildenafil on Mortality in Adults With PAH — NCT02060487.
• Registry record last updated 2022-05-13; status last verified 2022-05.
• Results first posted 2022-05-10.
• 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

This phase 4 study randomized 385 adults with pulmonary arterial hypertension among sildenafil 5 mg, 20 mg, and 80 mg groups, with dosing described as three times per day. It was parallel-group and quadruple-masked, and its status is terminated. The primary outcome was overall survival, reported as participant death counts over a maximum duration of 2102 days.

The registry record reports 34 deaths in the 5 mg group, 25 in the 20 mg group, and 19 in the 80 mg group. It also posts hazard-ratio analyses labeled non-inferiority, with 99.7% confidence intervals that include 1. Unadjusted re-calculations compare event proportions as risk differences. Secondary outcomes include clinical worsening and 6-minute walk distance at Month 6 and Month 12. Important details, including the primary analysis methods, non-inferiority margin, multiplicity plan, missing-data handling, interim analyses, and reason for termination, are not reported in the registry record.