Misoprostol 400 µg Versus 200 µg for Cervical Ripening in 1st Trimester Miscarriage: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Misoprostol 400 µg Versus 200 µg for Cervical Ripening in 1st Trimester Miscarriage (NCT02957305), a randomized phase 4 study. The primary outcome is Number of Participants Who Required Cervix Dilation at Initiation of the Manual Vacuum Aspiration.

2. Clinical Question

The clinical rationale in the registry summary is a comparison of cervical ripening with the two doses. It describes a local protocol recommending 400 µg 3 hours before uterine evacuation, and notes interest in whether a reduced dose could provide similar cervical dilation. The trial’s arm descriptions, however, specify that both doses were given at least 6 hours before the procedure. These are distinct details: the background describes the local protocol, while the arm descriptions give the timing used in the trial.

The primary outcome concerns a practical procedural event: whether a mechanical dilator was needed to open the cervix for manual vacuum aspiration. A separate secondary outcome concerns the presence of a uterine cervical canal with at least 8 mm of dilation. The record does not provide a primary-outcome estimate that would allow the size or precision of a between-arm difference to be evaluated.

3. Trial Design

This was a randomized, parallel-group, phase 4 clinical trial. The registry lists triple masking, but does not identify which roles were masked or describe how masking was maintained. It lists enrollment of 211 and a completed status. The sponsor is Hospital de Clinicas de Porto Alegre. The recorded study start date is 2016-12-21, and the primary completion date is 2019-10-19.

Participants were assigned to one of two intravaginal misoprostol regimens before manual vacuum aspiration. In the 400 µg arm, participants received two tablets of 200 µg each; in the 200 µg arm, participants received one 200 µg tablet. The descriptions specify administration at least 6 hours before the procedure in both arms. The trial therefore compares two dose regimens under the timing described for the study arms, rather than comparing the 6-hour timing with the 3-hour timing mentioned in the background.

Random allocation can, in general, help make treatment groups comparable at the start of a study by distributing known and unknown participant characteristics without a systematic assignment rule. The registry record does not report the sequence-generation method, allocation concealment procedure, blocking or stratification, or the details of how participants entered the assigned arms. Those aspects of the randomization process cannot be evaluated from the available record.

The primary outcome is the number of participants who required cervical dilation at initiation of manual vacuum aspiration. Its stated population is intention to treat, described as all participants assigned to either regimen. The record also lists a secondary outcome concerning cervical-canal dilation and says there were three outcome measures and three analyses, but the available information does not describe all outcomes, analytic methods, or the results for each analysis. The registry status is completed; that status alone does not supply the missing outcome estimates.

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: A total of 269 were screened. From these, 211 were enrolled and randomized to treatment. After randomization, 2 cases, one case of infected abortion and one case with previous cervical conization were identified and they were treated as for intention to treat.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intention to Treat Population (all participants assigned to misoprostol 400µg or 200µg)

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 Number of Participants Who Required Cervix Dilation at Initiation of the Manual Vacuum Aspiration, measured over baseline at initiation of the Manual Vacuum Aspiration.

The primary endpoint counts participants who required mechanical dilation to open the cervix when manual vacuum aspiration began. The registry describes the event as needing a mechanical dilator for appropriate performance of the procedure. It is measured at baseline at initiation of manual vacuum aspiration, where baseline refers to the stated procedural time point rather than an earlier study visit.

This endpoint is used to represent whether cervical opening was sufficient for the procedure without additional mechanical dilation. In general, a participant-level count can make a procedural outcome straightforward to interpret: each participant either meets the recorded event definition or does not. The endpoint is not itself a direct measurement of the amount of cervical opening for every participant. A separate secondary outcome addresses the presence of a cervical canal with at least 8 mm of dilation, but its results are not reported in the information.

The registry record identifies the primary endpoint and its intention-to-treat population, but does not report the group counts or a single primary-outcome comparison. The endpoint’s definition therefore establishes what the trial intended to measure, but does not establish how often dilation was required in either arm, whether the groups differed, or how precise any difference would be. Those conclusions require the outcome results and the corresponding analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to study groups using a chance-based process. In general, this helps limit systematic differences between groups at the time of assignment and supports a causal comparison when the trial is conducted and analyzed appropriately. It does not guarantee that every group characteristic will be identical, and it does not resolve problems such as missing outcome data, departures from assigned treatment, or incomplete reporting. The registry identifies the trial as randomized but does not report the sequence-generation or allocation-concealment methods, so those procedures cannot be assessed.

What does triple masking tell the reader?

The record labels the trial triple masked. Masking is intended, in general, to reduce the influence of knowledge about treatment assignment on participant experience, care, or outcome assessment. The registry record does not specify which people or roles were masked, how masking was maintained, or whether it was assessed. The label alone cannot establish that masking was successful or identify which potential sources of bias it addressed.

How should a participant count be understood?

The primary outcome is a count of participants who required mechanical cervical dilation at the start of manual vacuum aspiration. For a binary outcome, each participant is classified according to whether the specified event occurred. A group count gives the number with the event; interpreting it comparatively generally also requires the number assessed in each group, an effect measure, and an estimate of uncertainty. The available registry record does not give the primary-event counts or a summarized comparison, so none of those comparative quantities can be evaluated for this endpoint.

General statistical comparisons of binary outcomes can be expressed in several ways, including differences in event probability or relative measures. Each emphasizes a different aspect of the comparison. A confidence interval communicates uncertainty around an estimated effect: a narrower interval indicates greater precision under the assumptions of the analysis, while a wider interval indicates less precision. No primary-outcome effect estimate or interval is reported, so there is no basis to describe either the magnitude or precision of the treatment contrast.

What can the analysis population establish?

The primary outcome is described for an intention-to-treat population, defined in the record as all participants assigned to the two misoprostol regimens. In general, an intention-to-treat approach analyzes participants according to their randomized assignment, regardless of whether treatment was taken exactly as planned. This preserves the comparison created by randomization when implemented consistently. The registry description does not report how many participants had primary outcome data, how missing outcomes were handled, whether any participants were excluded from an analysis, or whether additional analysis populations were used. The label therefore describes the intended population but does not show how completely it was realized.

What is known about the statistical plan?

The registry lists three outcome measures and three analyses. It does not describe the statistical tests, effect measures, adjustment variables, model assumptions, analysis hierarchy, or treatment of missing data in the information available. It also does not report whether interim analyses were planned or conducted, or give a sample-size justification for the trial. These details are not reported in the registry record and should not be inferred from the study design label or enrollment figure.

General methods for binary outcomes can use a model for the probability of an event or a test comparing observed event frequencies. Model choice can affect the estimate and its uncertainty, especially when events are uncommon or counts are small. The registry does not identify a method for the primary endpoint, so it is not possible to describe which assumptions governed the reported analysis or whether any adjustment was made.

How do planning calculations differ from trial results?

Sample-size calculations are prospective planning tools. A planning illustration based on an observed effect is not a measurement of the trial’s observed power, and it does not replace the outcome analysis. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as a stated fraction of the observed effect. Such calculations depend on the assumed effect and other design inputs; they do not establish that the trial detected an effect or that an effect is clinically important. No sample-size illustration values or primary observed effect are reported in the information.

In general, post hoc power calculations based on an observed result do not add an independent assessment of evidence beyond the estimate and its uncertainty. A more informative interpretation focuses on the effect estimate, confidence interval, outcome definition, and limitations of the data. Because the primary-outcome comparison is not reported, those elements cannot be assessed for the central trial question.

How should the listed outcomes be kept distinct?

The primary endpoint concerns whether mechanical dilation was required. The secondary outcome concerns a cervical canal with at least 8 mm of dilation. These are related to cervical ripening but are not interchangeable measurements: one records a procedural need, while the other describes a dilation threshold. The registry does not report the results for the secondary outcome in the available information. A result for one outcome, even if it were available, should not automatically be treated as the result for the other.

When multiple outcomes or analyses are considered, multiplicity can increase the chance that at least one result appears unusual by chance if many tests are interpreted as confirmatory. In general, prespecified outcome hierarchies or statistical adjustments can address aspects of this issue. The record does not describe a multiplicity strategy or identify how the three analyses relate to the three outcome measures. It is therefore not possible to determine whether multiplicity was addressed or how the analyses were intended to support the primary question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but the available information does not identify every outcome, connect each analysis to a specific outcome, or describe an outcome hierarchy. A multiplicity adjustment or other strategy for handling multiple comparisons is not reported in the registry record. When several outcomes or tests are examined, general statistical interpretation should account for the possibility of chance findings across analyses. Without the analysis plan, the role of each result and the extent to which any result was confirmatory cannot be determined.

The primary outcome is stated for an intention-to-treat population, defined as all participants assigned to misoprostol 400 µg or 200 µg. The record does not report the amount of missing primary-outcome data, the reasons for any missingness, or the method used to handle it. It does not state whether a missing value was treated as an event, a non-event, excluded from analysis, or handled by another method. No sensitivity analysis for missing data is described in the available record.

The study is listed as randomized and triple masked, but the registry does not give details about treatment adherence, protocol deviations, withdrawals, or the number included in each analysis. It is therefore not possible to verify whether the stated intention-to-treat population included every assigned participant in the primary analysis. The record also does not report a per-protocol analysis or explain whether additional populations were used.

These omissions do not establish that the trial lacked an analysis plan or that missing data occurred. They mean only that the relevant details are not reported in the registry record available for interpretation. In general, transparent reporting of outcome definitions, analysis populations, missing-data handling, and multiplicity methods helps readers judge how robust a comparative result may be. Those judgments cannot be made for the primary comparison without the corresponding information and results.

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.

Most frequent non-serious adverse event terms

The registry separates serious adverse events, other adverse events, and deaths. In the 400 µg arm, the serious-event count is 0 among 106 participants at risk, the other-adverse-event count is 1 among 106 at risk, and the death count is 0. In the 200 µg arm, the serious-event count is 0 among 105 participants at risk, the other-adverse-event count is 3 among 105 at risk, and the death count is 0.

These are recorded counts, not a complete safety analysis. The registry record does not list serious adverse-event terms, and it does not specify the event types associated with the other-adverse-event counts. It also does not report event timing, severity detail for those events, duration of follow-up for safety, or a statistical comparison between arms. The number at risk is the denominator stated for each group; the figures should be read within their respective arms rather than combined into an overall count.

Zero recorded serious events and zero recorded deaths in both arms describe what the registry lists. They do not prove that no such events could occur or establish that the regimens have equivalent safety. The other-adverse-event counts are also too limited in description to support conclusions about the nature or comparative importance of those events. Safety interpretation remains constrained by the sparse event reporting and the absence of a detailed safety analysis.

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

The registry describes a randomized comparison of two intravaginal misoprostol doses before manual vacuum aspiration for first-trimester miscarriage. It identifies a clinically interpretable primary endpoint: whether a participant required mechanical dilation when the procedure began. It also records the intended primary analysis population and a secondary cervical-dilation outcome. These details explain what the trial was designed to examine.

They do not establish the comparative result. The primary-outcome counts, effect estimate, confidence interval, and test result are not reported in the available record. The secondary outcome result is also not reported. Accordingly, the information does not show whether the groups differed, how large any difference was, or how precisely it was estimated. It cannot establish that the doses produced similar outcomes, nor can it establish that one dose was better on the primary endpoint.

The study summary describes interest in whether a reduced dose could provide similar cervical dilation. A claim of non-inferiority or similarity requires an appropriate prespecified framework and a reported comparison interpreted against its criteria. The registry information does not report a non-inferiority margin or a primary analysis demonstrating that the outcome with 200 µg was acceptably similar to the outcome with 400 µg. The background rationale should not be mistaken for a trial finding.

The safety record lists zero serious adverse events and zero deaths in each arm, alongside other adverse events affecting one participant in the 400 µg arm and three participants in the 200 µg arm. These counts do not by themselves establish a safety difference or equivalence. Event descriptions and a comparative safety analysis are not reported in the available information.

In general, a trial result should be read through its outcome definition, effect estimate, uncertainty, analysis population, and data completeness. For this record, the design and question are described more fully than the outcome findings. The sound conclusion is limited: the trial compared the two regimens, but the registry information available does not permit a quantitative interpretation of the primary comparison.

13. Why This Trial Matters Statistically

This trial raises a statistical question about interpreting a randomized comparison when the registry describes the design and endpoint but does not report the primary result. Randomization supports a planned between-group comparison, yet readers still need the outcome counts and an estimate with uncertainty to understand what the comparison shows. Design information is not a substitute for results.

The endpoint also illustrates the difference between a procedural event and a measurement of anatomy. The primary outcome records whether mechanical dilation was needed at the start of manual vacuum aspiration, while the named secondary outcome uses a threshold for cervical-canal dilation. Both concern cervical ripening, but they answer different measurement questions. Reporting each outcome distinctly is important for statistical and clinical interpretation.

The registry’s description of an intention-to-treat population is useful because it signals the intended basis for the primary comparison. However, interpretation also depends on knowing whether outcome data were available for assigned participants and how missing observations were handled. Those details are not reported in the available information. The case therefore illustrates why naming an analysis population is informative but not sufficient to evaluate its implementation.

Finally, a stated interest in similar outcomes does not establish equivalence or non-inferiority. Such conclusions require a clearly defined statistical framework, an appropriate estimate, and adequate precision. Because the primary comparison is not reported, the record cannot support that kind of conclusion. The statistical importance of the trial lies in the question it sets up—and in the need for complete comparative reporting to answer it.

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 main limitation for interpreting this trial record is that the primary outcome is not reduced to a single comparison. The record names the outcome and describes its timing and population, but does not report arm-specific event counts, an effect estimate, a confidence interval, or a test result. The central comparative question therefore remains unanswered by the information.

The registry identifies three outcome measures and three analyses but does not describe the complete set of outcomes, the correspondence between outcomes and analyses, or any multiplicity strategy. Results for the named secondary outcome are not reported. The statistical methods for the primary endpoint, including any model, adjustment, or sensitivity analysis, are also not reported in the registry record.

Details that could affect interpretation are absent, including the randomization procedure, allocation concealment, which roles were masked, adherence, withdrawals, protocol deviations, missing-data handling, and the number contributing data to each analysis. The primary outcome is assigned an intention-to-treat population, but the record does not show how that population was implemented in the analysis. These details should not be assumed either present or absent in the underlying conduct of the trial.

The safety information is limited to group counts for serious adverse events, other adverse events, and deaths. Event descriptions are not available for the other-adverse-event counts, and no comparative safety analysis is reported. The background summary mentions a 3-hour timing recommendation, whereas the study-arm descriptions specify administration at least 6 hours before the procedure. The distinction is clear in the record, but the available information does not explain the reason for the trial timing or allow comparison of timing strategies.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Misoprostol 400 µg Versus 200 µg for Cervical Ripening in 1st Trimester Miscarriage — NCT02957305.
• Registry record last updated 2021-04-30; status last verified 2021-04.
• Results first posted 2020-09-03.
• 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

NCT02957305 is a completed, randomized, parallel-group, phase 4 trial sponsored by Hospital de Clinicas de Porto Alegre. The registry records enrollment of 211, triple masking, a study start date of 2016-12-21, and a primary completion date of 2019-10-19. The population is described as people with miscarriage in the first trimester.

The trial compared intravaginal misoprostol 400 µg with 200 µg, administered at least 6 hours before manual vacuum aspiration. Its primary outcome was the number of participants requiring mechanical cervical dilation at the start of the procedure, in an intention-to-treat population. A secondary outcome concerned the presence of a cervical canal with at least 8 mm of dilation.

The registry lists no serious adverse events and no deaths in either arm; other adverse events affected one participant in the 400 µg arm and three in the 200 µg arm. The available record does not report a single primary-outcome comparison, the secondary-outcome result, or details sufficient to assess missing-data handling and the statistical analysis plan.