Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing (NCT00626028), a randomized phase 3 study. The primary outcome is Number of Participants With Reversible Pulmonary Hypertension (Vasoreactivity).

2. Clinical Question

3. Trial Design

This is a Phase 3, randomized, unmasked crossover study. The registry describes enrollment of 136 participants and lists idiopathic pulmonary arterial hypertension and cardiomyopathy as conditions. The study is marked completed. Its recorded start is 2004-09 and its primary completion is 2010-02.

Participants were assigned to one of two sequences on Day 1. In the nitric-oxide-first sequence, the listed order was inhaled nitric oxide at 80 ppm, nitric oxide plus oxygen, a 10 minute washout, and 100% oxygen. In the oxygen-first sequence, the listed order was 100% oxygen, nitric oxide plus oxygen, a 10 minute washout, and inhaled nitric oxide at 80 ppm. Each treatment dose is described as lasting 10 minutes. The registry names nitric oxide for inhalation, oxygen, and nitric oxide plus oxygen as interventions.

A crossover design exposes participants to treatments in a sequence rather than assigning each participant to just one treatment throughout. Sequence and order therefore matter when interpreting group-level results. The posted primary comparison is between the two sequence groups; the registry does not report a paired participant-level analysis, a period-specific analysis, or an assessment of possible carryover effects. It also does not describe how sequence effects were handled statistically.

The primary endpoint population is described as all participants in the intent-to-treat analysis set who completed the study. The reported group counts for that outcome are 62 and 59. The reason the number in this analysis differs from the enrollment figure is not reported in the registry record. Details of the original sample-size justification, randomization procedure, and planned statistical analysis 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.

Before assignment: All 136 patients screened received all three study drugs in a crossover design, serving as their own controls. They were randomized 1:1 into two treatment sequences.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants in the intent to treat analysis set who completed the study

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: The intent-to-treat (ITT) population was defined as all participants randomized regardless of actual receipt of treatment gas, the treatment gas actually received, or the appropriateness of their enrollment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Reversible Pulmonary Hypertension (Vasoreactivity), measured over on Day 1.

The primary endpoint counts participants identified as having reversible pulmonary hypertension, also called vasoreactivity, during acute pulmonary vasodilator testing on Day 1. The registry describes the endpoint as based on a composite of hemodynamic measurements. The event is a participant-level classification: the recorded outcome is the number meeting the definition, rather than the size of a continuous change in an individual measurement.

Using a composite can bring multiple measurements into one clinically defined response classification. In general, a composite endpoint needs a clear definition because its result depends on which components are included and how they are combined. The specific measurements, thresholds, and classification algorithm are not reported in the registry record. Consequently, the posted count can be interpreted as the number classified as vasoreactive, but the underlying measurement-level pattern cannot be assessed from the registry entry.

The registry gives 28 participants in the nitric-oxide-first sequence and 16 in the oxygen-first sequence. The stated primary population comprises participants in the intent-to-treat analysis set who completed the study. This endpoint addresses the acute testing question described in the record; it is distinct from the later secondary outcomes concerning surgical procedures within 1 year and within 3 years.

7. Results Posted in the Registry

• Oxygen First, Nitric Oxide Last: 27.1% (16/59) versus 45.2% (28/62) on control; risk difference -18.0 percentage points (95% CI -34.8 to -1.2), risk ratio 0.60 (0.36–0.99); unadjusted two-proportion z-test p = 0.039.

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 Related Surgical Procedures Within 1 Year

• 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:
  • Oxygen First, Nitric Oxide Last: 35.6% (21/59) versus 71.0% (44/62) on control; risk difference -35.4 percentage points (95% CI -52.0 to -18.7), risk ratio 0.50 (0.34–0.73); 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 Oxygen First, Nitric Oxide Last than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants With Related Surgical Procedures Within 3 Years

• 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:
  • Oxygen First, Nitric Oxide Last: 10.2% (6/59) versus 19.4% (12/62) on control; risk difference -9.2 percentage points (95% CI -21.7 to 3.3), risk ratio 0.53 (0.21–1.31); unadjusted two-proportion z-test p = 0.156.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Oxygen First, Nitric Oxide Last and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover participants with related surgical procedures within 1 year and within 3 years, alongside registry-listed outcomes for adverse events and serious adverse events. The numerical surgical-procedure comparisons show lower observed counts in the oxygen-first sequence at both follow-up periods; the size and uncertainty of each comparison differ. The adverse event information is recorded separately as safety data.

These outcomes address events after the acute Day 1 vasoreactivity assessment, so they provide a different type of information from the primary endpoint. They do not explain the composite hemodynamic classification, and they should not be treated as direct replications of it. A pattern across distinct outcomes can be informative descriptively, but the registry summaries do not establish a common mechanism or a causal relationship between the acute classification and later procedures.

Secondary comparisons carry less inferential weight when their analyses are unadjusted and when the number of planned tests and any testing hierarchy are not reported. With multiple endpoints, some apparently notable results can arise by chance. The registry does not report multiplicity adjustment or sponsor analysis results for the posted secondary comparisons. The secondary estimates are therefore best read as exploratory descriptions of the recorded outcomes, rather than as independent confirmation of the primary result.

The registry lists four secondary outcome titles, while numerical secondary comparisons are available for surgical procedures within 1 year and within 3 years. Numerical results for the listed adverse event and serious adverse event outcome counts are not reported as secondary endpoint comparisons in the registry record; the available safety figures are described separately. This distinction matters because an outcome title does not itself supply an estimate or an analysis.

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

• Number of Participants With Related Surgical Procedures Within 1 Year
• Number of Participants With Adverse Events (AEs)
• Number of Participants With Serious Adverse Events (SAEs)
• Number of Participants With Related Surgical Procedures Within 3 Years

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

A risk difference compares the proportions of participants with an event in two groups. In this trial’s primary comparison, the reference group is the nitric-oxide-first sequence and the other group is the oxygen-first sequence. The reported estimate, -0.180, is the oxygen-first proportion minus the nitric-oxide-first proportion. A negative estimate indicates a lower observed event proportion in the oxygen-first sequence. The estimate is on the probability scale; it is not a count of participants.

Risk differences are useful because they express the absolute contrast between event proportions. Other measures can express a relative contrast, such as a risk ratio or odds ratio, but those answer a different question and can have a different scale. The posted primary comparison also includes relative measures, but the risk difference is the stated comparison metric. No conversion of one measure into another is needed to interpret the posted risk difference.

How should the confidence interval and p-value be read?

A confidence interval gives a range of values compatible with the observed data under the statistical method used. Its width conveys precision: a narrower interval indicates more precision than a wider interval, all else equal. For the primary risk difference, the interval is -0.348 to -0.013. The interval does not include zero, the value corresponding to no difference on the risk-difference scale. The unadjusted p-value is 0.039. A p-value measures how unusual the observed data, or more extreme data, would be under a specified null model; it is not the probability that the null hypothesis is true and does not measure the size or importance of an effect.

The registry labels the posted p-value unadjusted. It does not report whether the sponsor used a different analysis or whether this comparison was adjusted for the crossover structure. The estimates should be understood as the comparisons posted in the registry, not as a substitute for an undocumented analysis plan.

Why does crossover structure matter?

In a crossover study, participants receive conditions in an ordered sequence. Measurements from the same participant can be correlated, and responses can potentially depend on treatment order or period. General statistical methods for crossover data can use within-participant comparisons and account for sequence or period, when the required information is available. The registry reports two randomized sequences, but does not report participant-level paired results, period-specific outcomes, or an analysis describing how order and carryover were handled. The displayed summary counts alone cannot establish whether those design features were incorporated into the comparison.

What does the composite endpoint contribute?

The primary outcome is a binary participant-level classification built from a composite of hemodynamic measurements. Binary summaries make the number meeting the response definition easy to describe, but they do not show the underlying values or how close participants were to any threshold. A composite can capture more than one aspect of a response; its interpretation depends on its component rules. The registry does not report the specific measurements, thresholds, or combining algorithm, so the endpoint cannot be independently reconstructed from the entry.

What is the role of the posted secondary comparisons?

The secondary surgical-procedure outcomes are also binary counts, and their comparisons are posted as risk differences with confidence intervals and unadjusted p-values. These are distinct endpoints and timeframes, so they should not be conflated with the Day 1 vasoreactivity result. The registry’s secondary analysis listings do not include reported sponsor analyses. No adjustment for testing multiple endpoints is reported. General statistical practice treats multiple unadjusted comparisons cautiously because the chance of at least one apparently unusual result can increase when many hypotheses are examined. The registry does not state how many comparisons were planned or whether a hierarchy was prespecified.

For count outcomes, the event count and the number at risk are different quantities. A count such as the number of participants with an event must be read alongside the group size. A difference in raw counts alone can reflect unequal group sizes; the risk-difference comparison instead uses event proportions. The primary group sizes are 62 and 59, and the reported event counts are 28 and 16.

What is not documented?

The registry does not report the trial’s original sample-size justification, the planned significance level, its original statistical analysis plan, interim analyses, or its approach to missing data. It also does not report the method used for the posted confidence intervals or p-values. Those omissions prevent a full audit of prespecification, multiplicity handling, and design-specific modeling. The planning illustrations are separate from the trial’s original design assumptions and should be interpreted only as hypothetical planning calculations.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.180, with a 95% confidence interval from -0.348 to -0.013. The interval is entirely below zero, so the posted estimate is compatible with a lower event proportion in the oxygen-first sequence than in the nitric-oxide-first sequence under the stated comparison direction. The interval’s lower and upper limits also show that the size of the difference remains uncertain; the point estimate alone should not be treated as exact.

A confidence interval is a measure of statistical precision, not a range containing every participant’s response or a guarantee that the true effect lies within those particular limits. Its width reflects both the amount of information and the variability relevant to the method. The registry supplies no participant-level measurements, so the precision cannot be explored for the hemodynamic components separately.

The unadjusted p-value for the primary comparison is 0.039. This is consistent with the interval excluding zero for the posted risk-difference comparison, but it does not resolve concerns about analysis choices, multiplicity, or the crossover structure. No adjusted confidence interval or adjusted p-value is reported in the registry record.

The group counts are 62 and 59, with 28 and 16 participants meeting the endpoint, respectively. These are modest analysis-group sizes in relation to the range of possible event proportions, and the uncertainty is visible in the interval. The registry does not report additional sensitivity analyses or precision estimates for alternative endpoint definitions.

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 planning illustrations describe participants per arm for 80% power and participants per arm for 90% power. These are not total-event counts: the endpoint is a participant count, not a time-to-event outcome. For the primary endpoint, planning for 100% of the observed effect gives 111 participants per arm for 80% power and 147 participants per arm for 90% power. Planning for 75% of the observed effect gives 202 and 270 participants per arm, respectively; planning for 50% gives 465 and 621.

In plain terms, the 80% power column estimates a group size intended to give an 80% chance of detecting the specified effect under the planning model if that effect is real. The 90% power column uses a higher target chance of detection. These are planning targets, not guarantees about a future study’s result. The illustrations assume 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.

Smaller effects require more participants under these assumptions because a smaller contrast is harder to distinguish from random variation. The numbers are planning illustrations based on the observed effect, not observed power. The trial’s original design assumptions and sample-size justification are not reported in the registry record. The secondary planning values likewise depend on the observed effect for their respective endpoints and should not be read as evidence about how the original trial was designed.

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 = 0.452; treatment proportion p₁ = 0.271; average p̄ = 0.361.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6794 = 1.3316.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6673 = 0.5616.
4. n = (1.3316 + 0.5616)² / (-0.1804)² = 110.1, rounded up to 111 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 <- 0.451612903225806                          # control proportion
p1 <- 0.271186440677966                          # 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(626028)
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 = 111 (80% power), 147 (90% power)
 75% of observed effect: n per arm = 202 (80% power), 270 (90% power)
 50% of observed effect: n per arm = 465 (80% power), 621 (90% power)
power.prop.test: 110.1 
Simulated power at n = 111 per arm: 0.805 (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. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. It does not state how many primary hypotheses were planned, whether the secondary outcomes were tested formally, or whether a hierarchy or adjustment method was used. The posted p-values are unadjusted. When several outcomes are examined, unadjusted p-values do not control the overall chance of a false-positive finding across all tests. General statistical practice therefore treats secondary unadjusted results as less conclusive than a prespecified primary analysis.

The crossover design raises additional analysis questions. The record describes randomized treatment sequences, but does not report whether the primary analysis used within-participant pairing, accounted for period or sequence, or assessed carryover. It also does not provide the statistical model, test, or confidence-interval method used for the posted comparisons. These methods are not reported in the registry record.

The primary population is described as participants in the intent-to-treat analysis set who completed the study. The registry reports enrollment of 136 and primary outcome groups of 62 and 59. It does not report the disposition of participants between enrollment and this outcome population, the amount or pattern of missing data, or how missing outcomes were handled. The reason for the difference between enrollment and the primary analysis counts is not reported in the registry record. It would be inappropriate to infer that those participants withdrew, were excluded for a particular reason, or had a particular outcome.

The record also does not report interim analyses, stopping rules, protocol deviations, sensitivity analyses, or the trial’s original sample-size rationale. These omissions limit assessment of whether analyses were prespecified and how robust the findings are to alternative methods. They do not change the arithmetic of the posted summaries, but they restrict the conclusions that can be drawn from them.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: st segment elevation (1.6%), bradycardia (1.6%), pulmonary hypertension (1.6%), cardiac arrest (1.6%), hypotension (1.6%).

The serious adverse event figures are listed by randomized sequence. Three participants in the nitric-oxide-first sequence are recorded with serious adverse events among 62 at risk; none are recorded among 59 at risk in the oxygen-first sequence. The other adverse event counts are recorded as zero in both sequences. These are participant counts, not estimates of comparative risk adjusted for the crossover design.

The registry lists six serious event terms, each with a frequency of 1.6%: ST Segment Elevation, Bradycardia, Pulmonary Hypertension, Cardiac Arrest, Hypotension, and Low Cardiac Output Syndrome. The record does not provide further detail about event timing, severity grading, attribution, or whether terms overlap within participants. Death counts are not reported in the registry record.

These figures are descriptive safety summaries. They do not establish that a treatment or sequence caused an event, and the small numbers provide limited precision for comparisons. The registry does not report a formal statistical comparison for these safety counts.

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

The primary result describes the number of participants classified as having reversible pulmonary hypertension during acute pulmonary vasodilator testing. The recorded counts are 28 in the nitric-oxide-first sequence and 16 in the oxygen-first sequence. The associated unadjusted risk difference is -0.180 for oxygen first relative to nitric oxide first, with a 95% confidence interval from -0.348 to -0.013. These results describe the posted data and the endpoint definition as recorded.

The result does not establish how each hemodynamic component changed, because the registry does not provide the component measurements or the detailed composite algorithm. It also does not show whether a participant’s response differed between treatment periods. Although the study is described as a crossover, the registry does not report paired participant-level results or the handling of period and carryover effects. A sequence-level comparison should not be interpreted as though it were a complete within-participant analysis.

The acute endpoint is not the same as later surgical procedures or longer-term clinical outcomes. The secondary procedure outcomes have separate counts and unadjusted comparisons. They do not demonstrate that the Day 1 vasoreactivity classification predicts or causes later events. The safety counts are likewise descriptive and do not establish causal attribution.

The registry does not report the original statistical plan, missing-data approach, multiplicity adjustment, or sample-size justification. The posted p-value is unadjusted, and the reason the primary analysis group counts differ from the enrollment figure is not reported in the registry record. These gaps limit assessment of prespecification, robustness, and the relationship between the analyzed participants and all those enrolled.

Accordingly, the evidence supports a description of the observed counts and their uncertainty, not a medical recommendation or a definitive causal conclusion. The confidence interval quantifies uncertainty for the posted risk-difference comparison under its analysis, while unreported design and analysis details remain relevant to how strongly that comparison can be interpreted.

17. Why This Trial Matters Statistically

This trial is statistically notable because it combines a randomized crossover structure with a binary participant-level response outcome. A crossover can make within-participant comparisons informative, but sequence, period, and possible carryover effects matter. The registry reports group-level counts by randomized sequence, while not reporting whether the posted comparison used paired data or modeled those design features. That makes the distinction between the randomized sequence comparison and a within-participant treatment contrast especially important.

The endpoint is a composite classification based on hemodynamic measurements. Composite outcomes can condense several measures into a single event count, but interpretation depends on the component rules and thresholds. Because those details are not reported, the result cannot be unpacked into measurement-specific responses. This illustrates why a concise binary endpoint may be easy to summarize yet still leave important statistical and clinical structure unavailable.

The primary estimate has a confidence interval that excludes zero, but the p-value is unadjusted and the record does not document multiplicity handling or the original analysis plan. The finding is therefore best understood alongside the uncertainty and reporting gaps, rather than in isolation. The secondary outcomes further demonstrate why distinct follow-up endpoints should not automatically be treated as confirmations of an acute primary result.

Finally, the enrollment count and the endpoint analysis counts are not the same, and the registry does not give a participant disposition accounting. This highlights the importance of reporting analysis populations and missing-data handling, particularly in trials where the outcome is defined for participants who completed testing. The record permits careful description of posted summaries but leaves several aspects of design-specific inference unresolved.

18. 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.

Interpretation is limited by incomplete statistical and operational detail in the registry record. The primary endpoint is described as a composite of hemodynamic measurements, but its components, thresholds, and classification algorithm are not reported. Without these details, the event definition cannot be independently reproduced or evaluated for sensitivity to alternative criteria.

The study is a crossover trial, yet the registry does not report paired participant-level results, period-specific outcomes, or methods for addressing sequence and carryover effects. The posted group-level estimates may not convey the within-participant contrast that a crossover design can support. The original analysis plan and the method used to calculate the posted confidence intervals and p-values are also not reported.

The record gives enrollment of 136, whereas primary outcome groups contain 62 and 59 participants. Participant disposition, exclusions, and missing outcome handling are not reported, so the reason for the difference cannot be determined. The primary population is described as participants in the intent-to-treat analysis set who completed the study; that wording does not supply the missing accounting.

Multiplicity handling, interim analyses, the original sample-size justification, and planned sensitivity analyses are not reported. The secondary comparisons are unadjusted, which limits their role as confirmatory evidence. The safety summaries have small event counts and do not include detailed timing or attribution information. These are limitations of the available registry record, not evidence that a particular analysis or event did or did not occur.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing — NCT00626028.
• Registry record last updated 2019-12-20; status last verified 2016-09.
• Results first posted 2010-09-16.
• 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.

22. Record Summary

The registry describes a completed Phase 3 randomized, unmasked crossover study of inhaled nitric oxide and oxygen during acute pulmonary vasodilator testing. Enrollment was 136, and the listed conditions were idiopathic pulmonary arterial hypertension and cardiomyopathy. The primary outcome was the number of participants classified as having reversible pulmonary hypertension on Day 1, based on a composite of hemodynamic measurements.

The primary groups recorded 28 of 62 participants in the nitric-oxide-first sequence and 16 of 59 in the oxygen-first sequence. The unadjusted risk difference for oxygen first relative to nitric oxide first was -0.180, with a 95% confidence interval from -0.348 to -0.013 and an unadjusted p-value of 0.039. The registry also lists surgical-procedure follow-up outcomes and safety outcomes.

Details of the original statistical plan, crossover-specific analysis, missing-data handling, and multiplicity adjustment are not reported in the registry record.