Outcome of Cetrotide Therapy for Management of Women at High-risk of Ovarian Hyperstimulation Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Outcome of Cetrotide Therapy for Management of Women at High-risk of Ovarian Hyperstimulation Syndrome (NCT02823080), a randomized phase 2, phase 3 study. The primary outcome is Daily Serum E2 Levels.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group trial with enrollment of 48 women. It lists the trial as Phase 2 and Phase 3. The record describes a cetrotide group and a no-cetrotide control group, with 24 participants in each. The intervention was a 3-day course of subcutaneous cetrorelix acetate at 0.25 mg/day, starting on Day-0, the day of oocyte retrieval. Participants in the control group did not receive the study intervention.

The trial concerned women at high risk of ovarian hyperstimulation syndrome following a gonadotropin-releasing hormone agonist induction protocol. The summary says that patients underwent embryo freezing. Measurements listed in the description include daily serum E2 levels, pain scores, and maximal ovarian diameter. Hematocrit, total leucocytic count, gastrointestinal manifestations, and ascites grading were also assessed, with some reassessments specified for Day-3, Day-6, and Day-8. The registered primary outcome is daily serum E2 levels; the other listed outcomes include pain scores, hematocrit, ascites severity, and total leucocytic count.

The record gives a start date of 2014-10 and a primary completion date of 2017-04. Trial status is listed as unknown. Although randomization and triple masking are recorded, the randomization method, allocation concealment procedures, masking roles, and practical masking procedures are not reported in the registry record. The record also does not report details of recruitment, adherence, withdrawals, or the number of participants included in each outcome analysis. Those omissions limit assessment of how the planned group comparison was implemented.

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 Daily Serum E2 Levels, measured over 8 days.

The primary outcome is daily serum E2 levels, measured in picograms/ml. E2 refers to estradiol. The record describes daily measurement over a timeframe of 8 days and specifies that the outcome is summarized as a mean with standard deviation. This is a continuous measure: each participant has a numeric concentration rather than a result belonging only to a yes-or-no category.

In general, repeated measurements can describe how a continuous marker changes over time, rather than relying on a single measurement. In this trial’s context, the daily E2 course was intended to be assessed during the period after oocyte retrieval. The registry record does not state a single-day primary comparison or a summary measure combining the daily values, so it is not possible to tell from the record which part of the daily course would carry the main inferential emphasis.

Means describe the average observed values in a group, while standard deviations describe the spread of individual measurements around that group’s mean. These summaries do not, by themselves, establish whether groups differ, how precisely a difference is estimated, or whether changes are clinically important. The registry record does not report the primary-outcome values, group contrasts, confidence intervals, or statistical tests. Accordingly, the endpoint’s measurement plan can be described, but its observed result cannot be interpreted from the reported record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the study as randomized, triple-masked, and parallel-group. These design labels describe broad features, but they do not supply all the details needed to evaluate the analysis. In a randomized trial, assignment is intended to create groups whose baseline characteristics are comparable on average, subject to chance variation. The record does not state how the random sequence was generated, how assignments were concealed, or whether any departures from assigned treatment occurred. Triple masking indicates that masking was planned across three roles, but the roles and procedures are not reported in the registry record.

What does a mean and standard deviation describe?

The primary outcome is continuous serum E2, and the registered summary measure is the mean with standard deviation. In general, the mean is the arithmetic average of observed values. The standard deviation describes how dispersed individual values are around that mean. It is not the same as the uncertainty in the estimated mean: uncertainty also depends on the amount of usable data and the analysis. A mean and standard deviation can summarize a group at a time point, but repeated daily measurements raise a further question about how observations from the same participant are handled.

Why does the repeated-measure structure matter?

In general, measurements from one participant across days are likely to be related rather than independent. An analysis that recognizes this within-participant relationship can distinguish variation among participants from change or variation over time. Different valid approaches can target different quantities, such as a group difference at a particular time or an overall pattern across time. The registry record identifies daily measurement but does not report the statistical model, the planned contrast, or whether a group-by-time comparison was intended. It is therefore not possible to reconstruct the analysis from the outcome description alone.

For count-like or skewed data, the distribution and analysis may differ from those for a continuous outcome. That general consideration can matter for additional outcomes such as counts of blood cells or ordered severity grades, but the record does not state the distributions, models, or test procedures used for those outcomes. The outcome labels alone do not establish which statistical method was used.

How should uncertainty be read?

In general, a confidence interval expresses the uncertainty around an estimate under a specified method and its assumptions. A relatively narrow interval indicates greater precision than a wide interval, but it does not by itself establish clinical importance. A p-value is a measure based on the observed data and a statistical model under a null hypothesis; it is not the probability that the null hypothesis is true, and it does not measure effect size. The registry record does not report a confidence interval or p-value for the primary outcome, so neither precision nor statistical evidence for a difference can be assessed from these registry entries.

General statistical practice also distinguishes a prespecified primary outcome from additional outcomes. Prespecification can help clarify which comparison is the central one and reduce the risk of selective emphasis after many results are examined. The record identifies daily serum E2 as primary and lists secondary outcomes, but it does not report the full analysis plan, outcome hierarchy, or whether all planned analyses were completed.

What do the sample-size assumptions mean?

The registry record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such figures are planning illustrations, not observed power and not evidence that a study had a particular probability of finding a result. Sample-size requirements depend on the target effect and statistical assumptions. The record does not report the trial’s own sample-size justification, and no numerical planning result is available in the registry record.

In general, planning from an observed effect can be especially uncertain when the original estimate is imprecise. A smaller target effect than the observed estimate requires a different planning calculation, but the illustration should not be read as a guarantee of future results. Any planning figures should be understood as hypothetical participant counts under their stated assumptions, not as the number who actually experienced an outcome. The stated convention is participants per arm for non-time-to-event outcomes.

Over-dispersion is a general issue when observed variability exceeds what a simple statistical model assumes. If present, it can make standard errors and confidence intervals from an overly restrictive model too small. The registry record does not report whether over-dispersion was assessed or relevant to any outcome in this trial. More broadly, the statistical model, diagnostic checks, covariate adjustment, and handling of repeated measurements are not reported in the registry record, so model adequacy cannot be evaluated from the available description.

10. Multiplicity, Missing Data and Analysis Populations

The trial lists daily serum E2 as its primary outcome and identifies several secondary outcomes: daily numerical pain scores, daily hematocrit values, ultrasound-detected ascites severity from Day-0 to Day-8, and daily total leucocytic count. Repeated daily measurement creates multiple potential time-specific comparisons. Considering several outcomes and time points can increase the chance of at least one apparently notable result even when no underlying group difference exists. In general, multiplicity procedures or a prespecified hierarchy can help control how results are interpreted across those comparisons.

The registry record does not report a multiplicity adjustment, a hierarchy among time points, a single summary contrast for the daily E2 measurements, or a complete statistical analysis plan. It is therefore not possible to determine whether the analyses were adjusted for multiple comparisons or how any individual result was prioritized. The primary outcome designation is informative, but it does not resolve the unreported analysis details.

Missing-data handling is also not reported in the registry record. The record describes 24 participants in each group but does not give the number analyzed for the primary outcome at each day, the amount or reasons for missing data, or the methods used to address incomplete follow-up. In general, complete-case results can be affected if missingness is related to participant characteristics or outcomes; methods for incomplete repeated measurements rely on assumptions that should be described. No particular missing-data mechanism or method can be inferred from the record.

The analysis population is not reported in the registry record. It is not stated whether participants were analyzed according to randomized assignment, according to treatment received, or under another definition. There is also no reported accounting of withdrawals or protocol deviations. These gaps prevent assessment of whether the analysis retained the protection intended by randomization and how representative the analyzed participants were of those enrolled.

11. 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.

The registry record lists 24 participants at risk in each group for serious adverse events and 24 at risk in each group for other adverse events. It records zero affected participants for serious adverse events in the cetrotide group and zero in the no-cetrotide group. It also records zero affected participants for other adverse events in both groups, and zero deaths in both groups.

These are counts recorded in the registry, not a complete description of safety monitoring. The record does not provide event definitions, the observation period for the adverse-event counts, event-level details, or information about how events were collected and classified. Zero recorded events in these categories does not establish that no events occurred outside the registry’s reporting scope, nor does it establish that the risk is absent.

In general, safety estimates based on small groups can be imprecise, particularly for uncommon events. A zero count does not determine the range of possible underlying risks. The figures should therefore be read narrowly as the registry’s reported counts and denominators, not as a comparison establishing safety or as evidence about outcomes not listed in those categories.

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

The registry record establishes a research question and a design: a randomized, triple-masked, parallel-group comparison of a 3-day cetrotide regimen with no cetrotide in women described as being at high risk of ovarian hyperstimulation syndrome. It identifies daily serum E2 levels as the primary outcome and records a planned measurement timeframe of 8 days. It also describes other clinical and laboratory measurements and gives group counts of 24 participants each.

Those design details do not answer whether the groups had different E2 levels. The registry record does not report the daily values, a treatment-group estimate, a confidence interval, or a statistical test for the primary outcome. It also does not report comparative values for the listed secondary outcomes in the registry record described. A statistical interpretation of the observed treatment effect would require those results and information about the analysis used.

In general, an observed statistical difference would not by itself establish that a difference is clinically important. The size, precision, time pattern, and relevance of the outcome all matter. Conversely, a result that does not meet a statistical threshold would not establish that groups are identical; its interpretation would depend on the estimate and uncertainty. Here, because those outcome results are not reported in the registry record, neither kind of conclusion is supported.

The serious and other adverse-event counts are recorded as zero in both groups, as are deaths. These counts should be distinguished from a complete safety assessment and do not fill the gap in primary-outcome reporting. The record also does not state the analysis population or how missing daily values were handled.

The appropriate meaning is therefore limited to what the record documents: the intended comparison, the treatment schedule, the measured outcomes, and the reported adverse-event counts. It does not establish the direction, magnitude, precision, or clinical significance of a difference in serum E2 or other outcomes.

13. Why This Trial Matters Statistically

This trial raises a useful statistical issue because its primary outcome is measured repeatedly rather than only once. Daily serum E2 measurements can describe a changing course over time, but interpreting that course requires clarity about the comparison of interest. A single time-specific contrast, an average contrast across days, and a difference in trajectories are not interchangeable questions. The registry record gives the daily measurement plan but does not identify the primary statistical contrast.

The design also makes the distinction between a registered outcome and a reported result important. Naming an endpoint does not provide its observed values or establish the result. Without a group estimate and its uncertainty, readers cannot determine whether the data are compatible with a small or large difference, or with no meaningful difference. This illustrates why numerical outcome reporting is central to evaluating a trial.

Several outcomes and repeated time points can raise multiplicity concerns. A clear analysis plan can specify which outcome and contrast are central and how the rest will be interpreted. The registry record does not report those details, nor does it explain how missing daily observations were treated. These omissions matter because the analysis choices can affect both precision and the interpretation of evidence.

The record’s adverse-event counts also illustrate the limits of interpreting zero counts in small groups. They are useful as reported counts, but without fuller definitions, follow-up details, and uncertainty, they cannot characterize rare risks precisely. Taken together, this trial is statistically notable as an example of the difference between having a defined design and having sufficiently reported results for an effect estimate to be assessed.

14. 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 principal limitation for statistical interpretation is that the registry record does not report numerical primary-outcome results or a comparison between groups. The daily serum E2 values, effect estimates, confidence intervals, and p-values are not reported in the registry record. Consequently, the magnitude, direction, and precision of the primary outcome cannot be evaluated.

The record describes enrollment of 48 women and 24 participants in each group, but it does not report outcome-specific analysis counts, withdrawals, missing measurements, or a missing-data method. It does not identify the analysis population or say whether participants were analyzed according to randomized assignment. These omissions make it difficult to assess the extent to which the analyzed groups remained comparable.

Although randomization and triple masking are listed, the registry record does not describe the sequence-generation method, allocation concealment, masking roles, or masking procedures. It also does not report the statistical model, the specific primary contrast across days, any covariate adjustment, or how repeated measurements were handled. The multiplicity approach and the trial’s own sample-size justification are not reported in the registry record.

The trial status is listed as unknown. The adverse-event fields report zero affected participants for serious and other adverse events and zero deaths in each group, but event definitions, ascertainment details, and the observation period are not reported in the registry record. These limitations restrict assessment of both the outcome evidence and the completeness of safety reporting. They do not establish that an effect was absent; they mean that the relevant results and methods cannot be evaluated from the record described.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Outcome of Cetrotide Therapy for Management of Women at High-risk of Ovarian Hyperstimulation Syndrome — NCT02823080.
• Registry record last updated 2017-03-30; status last verified 2017-03.
• Results first posted 2017-01-31.
• 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.

18. Record Summary

The registry record describes a randomized, triple-masked, parallel-group Phase 2 and Phase 3 trial with 48 participants. It compares a 3-day course of subcutaneous cetrorelix acetate, 0.25 mg/day from Day-0, with no cetrotide in women described as being at high risk of ovarian hyperstimulation syndrome. The primary outcome is daily serum E2 levels in picograms/ml over a stated timeframe of 8 days.

Secondary outcomes include daily pain scores, hematocrit, ascites severity, and total leucocytic count. The record lists 24 participants in each group and records zero serious adverse events, zero other adverse events, and zero deaths in both groups. It gives a start date of 2014-10, a primary completion date of 2017-04, and a status of unknown.

Numerical primary-outcome results, group comparisons, analysis details, missing-data handling, and the analysis population are not reported in the registry record. The planned comparison and measurement schedule can be described, but the outcome effect and its precision cannot be assessed.