Therapeutic Effect of Desogestrel on Ventilatory Control in Patients With Congenital Central Hypoventilation Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Therapeutic Effect of Desogestrel on Ventilatory Control in Patients With Congenital Central Hypoventilation Syndrome (NCT01500473), a na phase 2 study. The primary outcome is Hypoxic Ventilatory Response.

2. Clinical Question

The study concerns whether desogestrel is associated with changes in ventilatory responses in females with CCHS. Its summary describes planned assessments of CO2 and oxygen responsiveness and spontaneous ventilation during sleep, with measures at baseline and after 3 weeks of treatment. The primary endpoint focuses on hypoxic ventilatory response, while the record lists 3 outcome measures overall.

The clinical question is therefore descriptive and within-group: what ventilatory measurements were observed during the study of desogestrel? Without a separate comparison group, the design cannot directly distinguish a change associated with treatment from changes due to time, measurement conditions, or other influences. The record does not give a numerical primary endpoint result, a treatment-effect estimate, or an account of why the study was terminated. Those details are not reported in the registry record.

3. Trial Design

This is a Phase 2, single-group study of desogestrel in females with congenital central hypoventilation syndrome. The registry lists allocation as not applicable and masking as none. The arm is described as females with CCHS >16 years old studied on drug, open label. Enrollment is listed as 1. The sponsor is Children's Hospital Los Angeles, and the registry status is terminated.

The study summary describes baseline measures followed by measurements after 3 weeks of taking a progesterone-containing oral contraceptive agent. Planned assessments included CO2 and oxygen responsiveness and spontaneous ventilation during sleep. The primary endpoint is hypoxic ventilatory response, defined in the record as an increase in minute ventilation as oxygen saturation of hemoglobin falls. The arm description identifies desogestrel as the intervention.

Because the study has a single group and no masking, its design does not provide a concurrent control for interpreting changes over time. The listed enrollment of 1 also means the record describes an extremely limited set of participant-level observations. That fact does not establish which measurements were completed or whether the participant contributed data to every outcome.

The registry gives a start date of 2012-02 and a primary completion date of 2016-05-11. It does not report the reason for termination, whether the planned assessments were all conducted, or whether the primary endpoint was analyzed. Detailed eligibility criteria, treatment dose, adherence, and the statistical analysis plan are not reported in the registry record. The study summary's stated rationale and hypotheses describe the investigators' intended questions, not evidence that the planned measurements produced a particular result.

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

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 Hypoxic Ventilatory Response, measured over 3 weeks.

The primary endpoint is Hypoxic Ventilatory Response, measured as subjects with a positive response. The registry defines a positive response as an increase in minute ventilation as oxygen saturation of hemoglobin falls, with a timeframe of 3 weeks. In general, minute ventilation describes the amount of air moved in and out of the lungs over time. A response measure of this kind records whether the specified change was observed, rather than reporting the size of the change in the endpoint description.

Assessing response to a hypoxic challenge can be used to characterize ventilatory control under reduced oxygen conditions. This is relevant to the study's stated focus on impaired automatic control of breathing in CCHS. That rationale explains why the endpoint was selected; it does not establish that the intervention changes the response.

The endpoint unit is subjects with a positive response, so interpretation depends on both the response definition and the number of participants assessed. The registry lists enrollment of 1 but does not report how many participants had an evaluable primary endpoint or whether a positive response was observed. The numerical endpoint result is not reported in the registry record. The record also does not provide a continuous measurement of the response's magnitude, a threshold beyond the described increase, or details of how the measurement was summarized.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that were actually used are not reported in the registry record. The record lists a single-group, open-label design, enrollment of 1, 3 outcome measures, and 0 analyses. The following concepts explain how such results are generally interpreted; they should not be taken as a description of an unreported analysis plan.

What does a single-group design estimate?

A single-group study can describe measurements in participants who received the intervention. If measurements are taken at baseline and again after treatment, a within-participant comparison can describe how those observed values differ. In general, such a comparison does not by itself isolate a treatment effect. Time, repeated testing, measurement variability, or other influences could also contribute to a change. A concurrent control group and random allocation can help address some of these alternative explanations, but neither is listed for this study.

Here, the summary describes baseline measures and assessment after 3 weeks, while the arm is described as open label on desogestrel. The registry does not report the participant-level measurements, whether paired measurements were available, or the method used to analyze them. It therefore cannot be established whether an actual within-person change was calculated.

How should a response count be read?

The primary endpoint is a count of subjects with a positive hypoxic ventilatory response. In general, a binary response endpoint classifies each assessed participant according to whether a prespecified response criterion is met. The count is meaningful only alongside the number assessed and a clear response definition. The record defines the response as increased minute ventilation as oxygen saturation of hemoglobin falls, but does not report a numerical endpoint count or the number with an evaluable measurement.

A count-based endpoint differs from a continuous measurement. A count can indicate how many participants met a criterion, while a continuous value can describe the size of an observed change. The endpoint description does not provide a continuous effect estimate or a threshold for the size of the increase. Any such details are not reported in the registry record.

What would a confidence interval contribute?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the chosen statistical method. It helps readers distinguish an estimate from the range of values that remain compatible with the data and method. A confidence interval does not correct for a weak design, missing measurements, or bias, and it does not establish causation. No confidence interval is reported for this study's primary endpoint, so its statistical precision cannot be evaluated.

What can a p-value establish?

In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions held. It is not the probability that a treatment works, and it does not measure the importance or size of an effect. A p-value also cannot substitute for an effect estimate and its uncertainty. No p-value or statistical test is reported in the registry record.

Why do analysis choices matter?

An analysis plan commonly defines the endpoint, the analysis population, how measurements are handled, and how uncertainty is quantified. Prespecifying those choices can reduce the risk of selectively emphasizing results. The registry lists 3 outcome measures but does not report a statistical analysis plan or analysis populations. It lists 0 analyses, so no analysis results are available in the record. The handling of missing data and any planned multiplicity adjustment are also not reported.

For a single-group study, interpretation should emphasize observed measurements and their limitations rather than infer a controlled treatment effect. General statistical practice would also consider whether the endpoint was measured consistently and whether the analysis matches the outcome's scale. The registry record does not provide enough methodological detail to determine what statistical procedures, if any, were applied.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Females With CCHS > 16 Years Old on Desogetrel")
n      <- c(1)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Females With CCHS > 16 Years Old on Desogetrel  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, but the statistical analysis plan and any multiplicity strategy are not reported in the registry record. In general, when several outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested separately without accounting for the number of analyses. A multiplicity approach may be prespecified to manage that issue, but no such approach is described. The record lists 0 analyses, and it does not report test statistics, p-values, or endpoint-specific estimates.

Missing-data handling is also not reported in the registry record. Enrollment is listed as 1, but the number with measurements available for each outcome is not given. The record does not say whether any test was incomplete, whether any participant withdrew, or how unavailable measurements would have been handled. Enrollment should therefore not be treated as the denominator for every endpoint without confirmation.

The analysis populations are not reported. The registry does not state which participants or measurements were included in an analysis, and it does not identify any intention-to-treat, per-protocol, or evaluable population. These are distinct analysis definitions in general; none should be attributed to this study without documentation. With no outcome counts or analysis details, neither the impact of missing measurements nor the consequences of analysis-population choices can be assessed.

12. 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 5% reporting threshold.

The registry lists 1 participant at risk for serious adverse events and 0 affected, and 1 at risk for other adverse events and 0 affected. It also reports 0 deaths. These are counts for the group described as females with CCHS >16 years old on desogestrel. No top serious-event terms are listed.

These figures describe what was recorded in this study; they do not establish that no adverse events occurred beyond the reporting captured in the registry. In general, a zero count in a small study provides limited information about the range or frequency of possible harms. It cannot rule out events that were not observed, events that were not recorded, or events that might occur in a larger or different population.

The record does not provide further detail about adverse-event definitions, collection procedures, severity grading, or follow-up. It also does not explain the study's termination. The serious and other adverse-event counts should therefore be read as registry-reported counts, not as a comprehensive estimate of safety.

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

The record establishes that a Phase 2, open-label, single-group study of desogestrel in females with CCHS was registered, with enrollment listed as 1 and status listed as terminated. It identifies hypoxic ventilatory response as the primary endpoint and describes planned assessments at baseline and after 3 weeks. It does not report a numerical result for that endpoint.

That distinction matters. A study question and a planned measurement are not results. Without a reported count of positive responses, measured values, or an estimate of change, the observed direction and magnitude cannot be determined. Without an uncertainty estimate, precision cannot be assessed. The registry also does not report a statistical test or analysis result.

The design does not include a separate control group or masking. In general, observations from a single group can describe what happened among participants measured, but they do not provide the same basis for causal comparison as a randomized controlled design. Even if a pre-treatment and post-treatment difference were reported, the record would need sufficient measurement and design details for readers to judge what that difference supports.

The listed adverse-event counts are 0 serious events, 0 other events, and 0 deaths, with 1 at risk in each event category. Those observations should not be interpreted as proof that the intervention has no risks. The study's listed enrollment is limited, and the registry does not provide enough safety-collection detail to characterize broader risk.

The study summary describes a rationale and hypotheses involving ventilatory responses and sleep ventilation. These describe the intended investigation, not findings. The reason for termination, actual completion of planned tests, endpoint evaluability, and analysis methods are not reported in the registry record. Accordingly, the record supports a description of the study's question and substantial evidential limits, but not a conclusion about whether desogestrel changed ventilatory control.

14. Why This Trial Matters Statistically

This study illustrates why the distinction between a registered question and a reported result is important. The registry gives a clear physiological focus: hypoxic ventilatory response, defined as increased minute ventilation as oxygen saturation of hemoglobin falls. It also describes other planned ventilatory assessments. Yet the primary endpoint's observed count is not reported, so the central result cannot be quantified from the registry record.

The design also shows how study structure shapes interpretation. A single-group, open-label study can describe observations in participants receiving an intervention, but it lacks a separate concurrent comparator. In general, the absence of a comparison group limits the ability to attribute a change specifically to treatment. Enrollment is listed as 1, further limiting how much can be learned about variation across participants or the precision of an estimate.

Statistically, the record makes missing analysis information visible. It lists 3 outcome measures but 0 analyses, and does not report a statistical analysis plan, analysis populations, missing-data procedures, or multiplicity handling. These details matter because readers need to know which observations were analyzed, how outcomes were defined and summarized, and how uncertainty was assessed. Without them, even a numerical result could be difficult to interpret fully.

The record also demonstrates why zero adverse-event counts should be read in context. The listed counts are useful descriptions of recorded events, but they do not provide a broad safety assessment with enrollment of 1. The study's design, enrollment, missing results, and unreported analysis details are central to understanding what the registry can and cannot establish.

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 primary limitation for interpretation is that the registry record does not report a numerical primary endpoint result. It also does not provide an endpoint denominator, participant-level measurements, an effect estimate, or an uncertainty interval. Thus, the observed response and its precision cannot be assessed.

Enrollment is listed as 1, and the study is single group, open label, and without a separate comparator. These features constrain how broadly observations could be interpreted and do not support a controlled treatment-effect comparison. The record does not establish whether all planned assessments were completed or whether the enrolled participant had evaluable data for every outcome.

The status is terminated, but the reason is not reported in the registry record. The detailed eligibility criteria, treatment dose, adherence, analysis populations, missing-data handling, statistical methods, and multiplicity strategy are also not reported. The registry lists 3 outcome measures and 0 analyses, leaving no analysis results with which to assess the planned hypotheses.

The study summary describes intended assessments and scientific rationale, but those plans should not be mistaken for completed measurements or findings. The available adverse-event counts are also limited by the enrollment and by the absence of detailed event-collection information. Together, these gaps prevent a quantitative assessment of efficacy, precision, or broader safety from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Therapeutic Effect of Desogestrel on Ventilatory Control in Patients With Congenital Central Hypoventilation Syndrome — NCT01500473.
• Registry record last updated 2023-11-18; status last verified 2023-10.
• Results first posted 2023-09-28.
• 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 a Phase 2, open-label, single-group study of desogestrel in females with congenital central hypoventilation syndrome. Enrollment is listed as 1, and the status is terminated. The study summary describes baseline and post-treatment ventilatory assessments, with the primary endpoint being the number of subjects with a positive hypoxic ventilatory response after 3 weeks.

The record does not report the numerical primary endpoint result, an analysis estimate, a confidence interval, or a p-value. It lists 3 outcome measures and 0 analyses. Serious adverse events, other adverse events, and deaths are listed as 0, with 1 at risk in each adverse-event category. The reason for termination and further statistical and missing-data details are not reported in the registry record.