Rapid Switch From Flolan to Remodulin in the Outpatient Clinic: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rapid Switch From Flolan to Remodulin in the Outpatient Clinic (NCT00643604), a non-randomized phase 4 study. The primary outcome is Change in Six Minute Walk Distance.

2. Clinical Question

3. Trial Design

The registry describes a phase 4, non-randomized, unmasked, single-group study. It enrolled 7 participants with pulmonary arterial hypertension. All subjects switched from intravenous epoprostenol to intravenous treprostinil sodium in an outpatient clinic. With no separate control group, the design evaluates change over time in the participants who switched; it does not directly compare the switch with continued epoprostenol or another concurrent treatment.

The stated study duration was 8 weeks. The primary endpoint was change in six-minute walk distance from baseline to Week 8. The primary endpoint description notes that two subjects had Week 8 visits outside the visit window and were included in the summary. It also notes that one subject died before Week 8 assessments. The registry record does not provide additional detail on how that death affected the primary endpoint analysis.

The study was terminated. The reason for termination is not reported in the registry record. The record lists 14 outcome measures and 23 analyses, including secondary outcomes concerning functional classification, dyspnea, treatment satisfaction, quality of life, time spent on activities associated with intravenous treatment, fatigue, and edema. The numerical findings for those measures are not reported in the record.

The registry does not report whether the study had a concurrent protocol, a prespecified statistical analysis plan, or a sample-size justification. Those details should not be inferred from the phase designation or the study’s stated objectives. The listed sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design; they do not establish how enrollment was planned or what analyses were actually performed.

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: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to Week 8 assessments.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Six Minute Walk Distance, measured over Baseline and Week 8.

The primary endpoint is change in six-minute walk distance, measured in meters from baseline to Week 8. It is a continuous measure: each participant’s result is a distance, and the study’s stated summary uses the mean with standard deviation. The endpoint is intended to capture change in walking performance over the study interval.

General statistical context: a walking-distance measure can provide a functional outcome that is distinct from a symptom rating or a treatment-satisfaction questionnaire. Repeated measurement allows a within-participant comparison over time. However, a change in the group mean does not show how much individual participants changed or whether the observed change was consistent across participants.

The record’s endpoint description identifies two Week 8 visits outside the visit window that were included in the summary and one participant who died before Week 8 assessments. These details matter when interpreting a change-from-baseline estimate because not all follow-up measurements necessarily occurred within the intended window, and a death before assessment is not simply an observed Week 8 distance. The mean change, standard deviation, confidence interval, and test result for the primary endpoint are not reported in the registry record. Consequently, the size and precision of any estimated change cannot be evaluated from the registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a mean, with standard deviation, for a continuous outcome: change in six-minute walk distance in meters between baseline and Week 8. It does not report the mean change, standard deviation, confidence interval, or primary test result. The following statistical concepts explain how such quantities are generally interpreted; they do not describe unreported procedures from this study.

What does a mean change represent?

General statistical explanation: a mean change is the average of participants’ individual differences between follow-up and baseline, using the direction defined by the analysis. It summarizes the group rather than showing each person’s trajectory. Participants can have changes in different directions, and the mean can conceal that variation. The standard deviation describes how dispersed individual changes are around their mean. It is not the same as the uncertainty around the estimated mean.

The registry’s stated summary is a mean and standard deviation, but the record does not provide the values. It also does not specify in the primary endpoint description whether the analysis used each participant’s paired measurements, how any missing baseline or follow-up measurements were handled, or whether adjustments were made. Those details are not reported in the registry record.

What would a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval’s location relative to a meaningful reference can help assess which values are compatible with the data and model. A confidence interval does not eliminate bias from a design without a control group, and it does not establish that an observed change was caused by the treatment switch.

No confidence interval for the primary endpoint is reported in the registry record. Without an estimate and its uncertainty, the magnitude and precision of the endpoint cannot be assessed. A p-value alone, if one were available, would not describe the size of the change or its practical importance; the registry record does not report a primary p-value either.

Why does the single-group design matter?

General statistical explanation: in a single-group before-and-after study, the observed change combines any effect associated with the intervention and other changes that occur during the same period. Those may include changes in participants’ condition, measurement circumstances, or other care. A concurrent comparison group can help distinguish treatment-related differences from time-related changes, although the quality of that comparison depends on design and analysis. This study had no separate comparator, so its design cannot provide that direct contrast.

Non-randomized allocation and absence of masking further mean that the study does not use random assignment or masked assessment as protections against certain forms of bias. The registry record does not describe additional procedures that might have been used to address these issues. The findings should therefore be read as observations from the enrolled group, not as a randomized estimate of a treatment contrast.

What do the planning assumptions mean?

The registry metadata describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes detecting a stated fraction of the observed effect. This is an illustrative planning framework, not the trial’s own design: the actual study was single-group, and the record does not report a sample-size justification. The numerical planning results are not reported in the registry record.

General statistical explanation: planning illustrations explore how a hypothetical future comparison might be sized under stated assumptions. Their outputs are not observed participant counts from the trial, and they are not evidence that the enrolled study had a particular probability of detecting an effect. In particular, an illustration based on an observed effect should not be described as observed power. The registry does not report enough information to assess the assumptions or translate that illustration into a statement about the trial’s ability to detect a change.

What can the outcome and analysis counts tell readers?

The registry lists 14 outcome measures and 23 analyses. Those counts indicate that multiple outcomes and analyses are part of the record, but do not disclose which statistical tests were used, whether outcomes were ranked or prioritized beyond the primary designation, or whether any adjustment for multiple testing was applied. The analysis plan and multiplicity procedures are not reported in the registry record. General statistical explanation: when many hypotheses are assessed, the chance of at least one apparently unusual result can increase if each is judged independently. An adjustment or a clear distinction between confirmatory and exploratory analyses can help readers interpret that setting, but no such procedure can be assumed.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Treprostinil Sodium")
n   <- c(6)
m   <- c(-14)
sp  <- c(63.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Treprostinil Sodium  6  -14.000  63.700  -80.849  52.849

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and 23 analyses. The primary endpoint is change in six-minute walk distance; the listed secondary outcomes include functional classification, dyspnea, quality of life, treatment satisfaction, fatigue, edema, and time spent on activities associated with intravenous treatment. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or which analyses were intended to be confirmatory. Without that information, statistical significance across multiple analyses, if reported elsewhere, would need to be interpreted cautiously. General statistical context: testing many outcomes can increase the chance of a nominally notable result arising by chance when each test is treated separately.

The primary endpoint description says two participants had Week 8 visits outside the visit window and were included in the summary. It also says one participant died before Week 8 assessments. The record does not explain how the death was handled analytically, whether any other endpoint data were missing, whether values were imputed, or what analysis population was used. It does not report whether the timing of the two out-of-window visits affected their measurements or how visit windows were defined.

General statistical context: missing measurements can affect both the number of observations contributing to an estimate and the interpretation of that estimate. A death before follow-up is a distinct event, not simply an unobserved measurement, and choices about how to incorporate it can change the question being answered. The registry does not report the methods needed to evaluate those choices for this endpoint. Since the mean change and its uncertainty are also not reported, the available record does not permit a complete assessment of the primary analysis.

12. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (14.3%), bacteraemia (14.3%), dehydration (14.3%), nausea (14.3%), vomiting (14.3%).

For the treprostinil sodium group, 7 subjects were listed as at risk for serious adverse events, and 2 were listed as affected. For other adverse events, 7 were listed as at risk and 6 as affected. These are counts of subjects affected in the registry record; they should not be read as counts of all individual event episodes.

The registry lists abdominal pain, bacteraemia, dehydration, nausea, and vomiting among the top serious adverse event terms, each at 14.3%. The entry does not provide further detail in these figures about timing, duration, severity, recurrence, or whether an event was judged related to treatment. The percentages should be read as registry-listed values, not as evidence that the events were caused by the switch.

The adverse-event record shows deaths as null, which does not establish that there were no deaths. Separately, the primary endpoint description states that one subject died before Week 8 assessments. The registry does not report additional circumstances or an attribution for that death. With an enrollment of 7 and no control group, these safety counts describe events recorded among a small group; they cannot by themselves establish comparative risk or causation.

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

This study asks a clinically focused question about switching from intravenous epoprostenol to intravenous treprostinil sodium in an outpatient clinic. It identifies change in six-minute walk distance as its primary endpoint and includes outcomes related to symptoms, treatment satisfaction, quality of life, and treatment activities. The registry also records adverse-event counts for the treprostinil sodium group.

What the record does not establish is the size or direction of the primary endpoint change. The mean change, standard deviation, confidence interval, and test result are not reported in the registry record. Without those statistics, the primary endpoint cannot be used to quantify how participants’ walking distances changed or how precisely a group estimate was measured. The record’s statement that two out-of-window Week 8 visits were included and one participant died before Week 8 assessments adds relevant context, but does not explain the analysis handling.

The design cannot answer a comparative causal question. All participants switched treatment, and there was no separate control group, randomization, or masking. An observed change over time in this group would not isolate the effect of switching from other influences. The enrollment of 7 also means that any group-level estimate would reflect a small set of participants and could be sensitive to individual observations.

The safety figures are descriptive. They report subjects affected by serious and other adverse events, and the registry lists several serious adverse event terms at 14.3%. These observations do not establish that the switch caused an event, and there is no concurrent group in the study against which to compare event frequency.

Accordingly, the registry record describes the question, design, outcomes, and selected safety information, but it does not provide the numerical primary outcome needed to characterize the observed change. It also does not provide enough methodological detail to assess missing-data handling, multiplicity procedures, or a prespecified analysis plan. Conclusions should stay within those limits.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question concerns change over time in a small, single-group study. The design is suited to describing what was observed among participants who switched, but without a separate comparator it cannot distinguish a treatment-associated change from other changes over the same period. That distinction is central when interpreting before-and-after outcomes.

The primary outcome is continuous and summarized as a mean with standard deviation. General statistical context: reporting both an estimate and a measure of uncertainty helps readers distinguish the size of an observed change from its precision. In this case, the registry record identifies the measure and summary type but does not report the numerical endpoint result or its uncertainty. The study’s primary clinical question therefore cannot be evaluated quantitatively from the record.

The record also highlights issues that matter in small studies: two Week 8 visits outside the window were included in the summary, and one participant died before Week 8 assessments. These are not interchangeable follow-up circumstances. Without an explanation of the endpoint analysis population and handling of the death, readers cannot fully assess how follow-up information contributes to the result.

Finally, the record lists 14 outcome measures and 23 analyses, but does not report multiplicity procedures or a statistical analysis plan. The counts make clear that the endpoint sits among several analyses, while leaving the planned interpretation of those analyses uncertain. Taken together, the study illustrates why design, follow-up, analysis methods, and uncertainty estimates are all necessary for interpreting a clinical outcome—not just the endpoint label or whether a numerical result is available.

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.

The study’s most direct limitation is its single-group, non-randomized, unmasked design. All subjects switched from intravenous epoprostenol to intravenous treprostinil sodium, with no concurrent control group. Any within-group change cannot serve as a direct estimate of the difference between switching and an alternative treatment strategy.

The enrollment was 7. This limits the amount of information available for describing variation across participants and makes group summaries potentially sensitive to individual observations. The registry record does not report participant characteristics that would allow readers to assess how closely the enrolled group represents a broader population of people with pulmonary arterial hypertension.

Follow-up was not uniform in relation to the stated Week 8 assessment: two visits outside the visit window were included in the summary, and one participant died before Week 8 assessments. The registry does not report the analysis population, the handling of the death, other missing-data details, or the effect of out-of-window visits. The mean change and its variability are not reported, so the endpoint cannot be assessed for magnitude or precision.

The record lists multiple outcomes and analyses but does not report the statistical analysis plan, multiplicity procedures, or a sample-size justification. It also does not report why the study was terminated. The adverse-event information is descriptive and does not provide a concurrent comparison or establish attribution. These gaps limit interpretation of both the clinical outcomes and safety observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rapid Switch From Flolan to Remodulin in the Outpatient Clinic — NCT00643604.
• Registry record last updated 2024-01-03; status last verified 2013-06.
• Results first posted 2013-06-21.
• 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.

19. Record Summary

The registry record describes NCT00643604, a phase 4, non-randomized, unmasked, single-group study titled Rapid Switch From Flolan to Remodulin in the Outpatient Clinic. It enrolled 7 participants with pulmonary arterial hypertension. All subjects switched from intravenous epoprostenol to intravenous treprostinil sodium in an outpatient clinic, with an intended study duration of 8 weeks. The record lists the study as terminated.

The primary endpoint was change in six-minute walk distance, measured in meters from baseline to Week 8 and summarized as a mean with standard deviation. Two Week 8 visits outside the visit window were included in the summary; one subject died before Week 8 assessments. Numerical primary endpoint results are not reported in the registry record.

The registry lists 14 outcome measures and 23 analyses. It records 2 subjects affected by serious adverse events and 6 affected by other adverse events, among 7 at risk in each category. A sample-size planning illustration is described, but it is not the study’s own design. The reason for termination and further analysis details are not reported in the registry record.