RCT for Women With a Persisting Pregnancy of Unknown Location: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RCT for Women With a Persisting Pregnancy of Unknown Location (NCT01800162), a randomized phase 1, phase 2 study. The primary outcome is Frequency of Clinical Resolution for the 3 Different Management Arms for a Persisting PUL..

2. Clinical Question

The trial addressed a comparison of management approaches for a persisting pregnancy of unknown location, a condition associated in the record with risk of ectopic pregnancy. Its primary question concerned clinical resolution across the three strategies, rather than a single pairwise comparison. The registry summary describes the intended outcome as an uneventful decline of hCG to 5 IU/mL. It also lists secondary questions about ruptured ectopic pregnancies, re-interventions, complications and adverse events, procedures, visits, time to resolution, preferences, and acceptability.

The record does not supply outcome results that could answer whether one strategy had a higher resolution frequency or differed on any secondary outcome. It reports that the study closed early, that data were not analyzed, and that patients were not followed for outcome. Consequently, the clinical question remains unresolved in the registry results; the recorded design and enrollment do not establish comparative effectiveness or safety.

3. Trial Design

This was a randomized, parallel-group trial with no masking. The registry lists phase 1 and phase 2 and identifies the study as terminated. The sponsor was the University of Pennsylvania. The recorded enrollment was 2. The study start is listed as 2013-02 and primary completion as 2013-12.

The intended comparison involved three strategies. In the uterine-evacuation strategy, participants would undergo evacuation and receive methotrexate if hCG did not decrease sufficiently afterward. The empiric methotrexate strategy specified a dose on day 0 and a subsequent dose on day 4, with additional doses as needed based on hCG. Expectant management involved serum hCG monitoring. The registry describes planned randomization in a 2:2:1 ratio across these strategies.

These details describe the intended design, not necessarily the treatment actually received by participants. The registry does not report arm-specific enrollment or confirm how many participants were randomized to each strategy. Nor does it report whether the planned treatment procedures were carried out. The primary outcome was intended for assessment within 6 weeks of randomization, but the outcome description says patients were not followed for outcome and the study was closed early.

Although the record lists ten outcome measures, it lists no analyses. The randomized design would ordinarily support comparisons between assigned groups, but interpretation depends on having outcome data, a specified comparison, and an analysis appropriate to the design. Those results are not available in the registry record. The available information therefore supports describing the trial's planned structure and its early closure, not estimating treatment effects.

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: Subjects must be 18 years or older. Subject must have a positive pregnancy test but no signs of pregnancy visualized in the uterus or adnexa on ultrasound? Subject must have at least three serial hCG values over the past 4-14 days or two serial hCG values over the past 7-14 days. Subject must be hemodynamically stable with a hemoglobin \>10mg/dL.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome.

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 Frequency of Clinical Resolution for the 3 Different Management Arms for a Persisting PUL., measured over Outcome will be assessed within 6 weeks of randomization.

The primary endpoint was the frequency of clinical resolution for the three management arms. The registry states that the outcome was to be assessed within 6 weeks of randomization. The brief summary describes the primary outcome as an uneventful decline of hCG to 5 IU/mL. The endpoint therefore centers on whether the pregnancy resolves according to the specified hCG criterion within the assessment period.

General: A defined clinical endpoint gives a trial a consistent outcome to compare across assigned groups. An hCG-based resolution measure can capture the course of a pregnancy of unknown location using a laboratory marker, while the specified time window makes clear when the outcome is assessed. The registry record does not further define “uneventful,” explain how the hCG decline was to be classified, or state how clinical resolution was operationalized across all circumstances.

The endpoint is not reported as an analyzed result. The record says the study closed early, data were not analyzed, and patients were not followed for outcome. Thus, the stated endpoint explains what the trial intended to measure, but the registry cannot show how often it occurred in any arm or how precisely the arm-specific frequencies could have been estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General: Randomization assigns participants to strategies by chance. When implemented as planned, it can reduce systematic differences between groups in both measured and unmeasured characteristics, supporting a fair comparison. It does not ensure that groups are identical, and its benefits are difficult to assess when enrollment and outcome data are very limited.

The registry identifies this study as randomized and parallel, with a planned 2:2:1 allocation across three strategies. It does not report arm-specific enrollment or confirm the allocation actually achieved. The method used to generate the random sequence, any concealment procedures, and details of implementation are not reported in the registry record. The planned allocation ratio should therefore not be treated as a description of the participants' actual distribution.

What does a parallel-group design mean?

General: In a parallel-group trial, each participant is assigned to a strategy and outcomes are compared between groups. The design differs from a crossover study, in which participants receive multiple treatments in sequence. Here, the three named arms represent distinct management approaches. The registry describes follow-up and clinical treatment according to the progression of each participant's condition, but does not report that the planned follow-up or outcome assessment was completed.

What does no masking imply?

The record lists masking as none. General: Masking means keeping participants, clinicians, or outcome assessors unaware of assigned treatment when feasible. Without masking, knowledge of the assigned strategy may influence care, reporting, or assessment. The potential relevance depends on the outcome and how it is measured. The registry does not describe any separate blinded assessment process, so one should not assume that outcome assessment was masked.

How should an outcome comparison be interpreted?

General: A comparative analysis requires outcome information for participants and a clear definition of the estimand, meaning the treatment effect the analysis aims to describe. For a randomized trial, one common approach compares outcomes according to the assigned strategy, whether or not all assigned treatment was received. Other approaches may focus on treatment received or on participants who completed follow-up, but they can answer different questions and may be vulnerable to bias.

The registry does not report an analysis population or an approach to deviations from assigned treatment. More fundamentally, the primary outcome description states that patients were not followed for outcome and data were not analyzed. No effect estimate, standard error, confidence interval, or p-value is reported. There is consequently no statistical result on which to base an arm comparison.

What do statistical significance and precision mean in general?

General: A p-value describes how incompatible the observed data are with a specified statistical model under a null hypothesis; it is not the probability that the null hypothesis is true. A confidence interval conveys uncertainty around an effect estimate. A small p-value alone does not establish that an effect is important, and a non-significant result does not prove that groups are equivalent. Both require interpretable data and a suitable analysis. Neither a p-value nor a confidence interval for the primary result is reported in this record.

Interpretation also depends on the scale of the outcome and the contrast being estimated. For a frequency outcome, an analysis might compare group-specific proportions or a difference between proportions, but the choice and its assumptions need to be stated. The registry identifies a three-arm primary outcome and a multi-category reduction that was not made into one comparison. It does not report a specific pairwise or overall statistical contrast. No unreported contrast should be inferred from the arm descriptions.

What are the sample-size illustrations?

General: A sample-size calculation is a planning exercise that describes the amount of information a future study might need under stated assumptions. It is not a result from the trial and does not measure the probability that this completed study detected an effect. The registry's stated illustration assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a fraction of the observed effect. The record also distinguishes illustrations for time-to-event outcomes from those for other outcomes.

Those assumptions are described as a planning illustration computed from the observed effect, not as the trial's own design. Since no primary outcome effect was analyzed or reported, such an illustration cannot be interpreted as a trial-specific, evidence-based design justification. It must not be described as observed power. The registry does not report the original sample-size justification or a statistical plan; those details are not reported in the registry record.

Why does the lack of outcome data matter?

General: Statistical methods quantify uncertainty in observed information; they cannot recover outcomes that were not collected. Early closure and lack of follow-up leave the primary question unanswered rather than producing a null finding. The recorded enrollment of 2 also indicates that the study did not generate a substantial comparative outcome dataset, but it does not by itself reveal why the trial closed or what each participant experienced.

The record does not report an interim analysis, stopping boundary, planned adjustment for multiple comparisons, or missing-data method. Without outcome follow-up, even a sophisticated analysis plan would not yield the intended endpoint comparison. The principal statistical conclusion is therefore about the limits of available evidence, not about the relative performance of the three strategies.

10. Multiplicity, Missing Data and Analysis Populations

The trial planned three management arms and lists a primary outcome along with secondary outcomes covering ruptured ectopic pregnancies, re-interventions, complications and adverse events, procedures, visits, time to resolution, preferences, and acceptability. The record lists ten outcome measures, but it does not report analyses. It also does not specify a single pairwise contrast or an overall test for the three-arm primary question.

General: When a study evaluates several outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase. A statistical plan may address this multiplicity by defining a primary comparison, controlling error rates, or treating secondary results as exploratory. Which approach is appropriate depends on the study question. A multiplicity strategy is not reported in the registry record, and no result-level interpretation is possible without analyzed outcomes.

Missing-data rules, analysis populations, handling of participants who discontinue or deviate from assigned treatment, and imputation methods are not reported in the registry record. The primary outcome description says patients were not followed for outcome, so the central limitation is more fundamental than a specified method for handling occasional missing observations: the intended primary outcome was not obtained as reported.

The record does not report an interim analysis or a statistical stopping rule. The study status is terminated, and the outcome description attributes the lack of analysis to early closure. The reason for closure and any decision-making process around termination are not reported in the registry record. These gaps prevent assessment of how multiplicity, missing data, or analysis populations would have been handled.

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 adverse-event entries list uterine evacuation and expectant management. For each listed group, the registry records 1 at risk, 0 affected by serious adverse events, 0 affected by other adverse events, and 0 deaths. These are the counts recorded in the registry and should be interpreted as sparse descriptive information.

A zero count in a small recorded group does not show that an event is impossible or that a strategy is free of risk. General: When few participants are observed, even a genuine event may not occur in the observed group; the data can therefore be compatible with substantial uncertainty about event frequency. A risk estimate or a meaningful comparison would require adequate outcome ascertainment and an analysis appropriate to the data.

The registry does not provide an adverse-event group entry for empiric methotrexate in the listed safety information. It also does not provide detail about the types of non-serious events, observation duration, or completeness of safety follow-up. The primary outcome description says patients were not followed for outcome, and safety entries should not be treated as evidence of complete safety surveillance. These figures cannot support a comparative safety conclusion among all three strategies.

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

The record establishes that a randomized, parallel-group trial was planned to compare three approaches for women with a persisting pregnancy of unknown location. It describes the treatment strategies, the intended hCG-based primary endpoint, and a range of secondary outcomes. The record also states that the study closed early and that primary outcome data were not analyzed because patients were not followed for outcome.

That means the registry does not report whether clinical resolution occurred, how often it occurred in each arm, or whether any arm differed from another. There is no reported treatment-effect estimate or uncertainty interval. The listed safety counts are limited to two group entries and do not establish comparative safety. No conclusion about benefit, harm, or equivalence can be drawn from the absent outcome analysis.

General: Failure to report a difference is not the same as evidence that there is no difference. A conclusion of similarity or equivalence requires a suitable design, defined margins where relevant, and data precise enough to rule out meaningful differences. This record does not contain analyzed outcome data for such an assessment.

The study's planned allocation ratio and the recorded enrollment do not tell readers how many participants were assigned to each arm or what treatment they received. Nor do they indicate the reason for termination. Those details are not reported in the registry record. The most defensible interpretation is that the trial's intended comparative question remains unanswered in its posted results.

The registry's sample-size assumptions are described as planning illustrations based on an observed effect, not as the trial's original design. They are not a substitute for observed outcomes and should not be read as evidence that the study had adequate power or that it detected an effect. The record supports a description of design and reporting limitations, not a clinical recommendation.

13. Why This Trial Matters Statistically

This trial is statistically notable because its record separates a detailed planned comparison from the absence of analyzable outcomes. Randomization and a defined primary endpoint can support a rigorous comparison when participants are followed and outcome data are available. Here, the registry states that the study closed early, data were not analyzed, and patients were not followed for the primary outcome. Design features alone cannot answer the clinical question.

The record also illustrates why enrollment counts and allocation plans are not outcome evidence. The enrollment recorded is 2, while the intended arm allocation was 2:2:1. Those details do not reveal the actual distribution across groups, completed treatment, or endpoint status. Statistical comparisons depend on observed data, not on the intended allocation scheme.

General: Sparse data often yield imprecise estimates, and incomplete follow-up can prevent estimation altogether. Precision concerns how much uncertainty surrounds a result; lack of an analyzed result means there is no estimate to evaluate. This distinction matters: a study with an uncertain estimate and a study with no reported estimate present different evidentiary situations.

The posted safety entries reinforce the need to keep descriptive counts in context. Zero recorded events in the two listed groups cannot establish absence of risk, especially when the available safety information is limited and no corresponding methotrexate group entry is listed. The record does not support a comparative safety analysis.

For biostatisticians and clinical researchers, the key lesson is that a registry's design and outcome definitions should be read alongside its analysis status and follow-up reporting. In this case, the record is informative about what was planned and what was not reported, while leaving the trial's primary comparative question unresolved.

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 trial-specific limitation is that the primary outcome was not analyzed. The registry says the study closed early, that analysis was not anticipated, and that patients were not followed for outcome. Consequently, the intended clinical-resolution endpoint has no reported arm-level result. The record cannot support estimates of effect or precision.

The recorded enrollment is 2, but the registry does not report arm-specific enrollment or the actual allocation achieved. It does not establish whether the planned strategies were administered or whether participants completed any treatment or assessment. The reason for early closure is not reported in the registry record.

The record identifies a primary outcome and multiple secondary outcomes but lists no analyses. It does not report a statistical analysis plan, a defined primary contrast, handling of missing data, analysis populations, or a strategy for multiplicity. It also does not report whether any interim analysis took place. These omissions prevent evaluation of planned inferential choices, although the absence of outcome follow-up is the more immediate obstacle.

Safety reporting is limited to entries for uterine evacuation and expectant management, with no methotrexate group entry in the listed information. The registry does not describe the completeness or duration of safety ascertainment. The small recorded enrollment and sparse safety counts make the entries unsuitable for a broad comparison of risks.

The primary outcome description does not further define “uneventful” resolution or explain how the endpoint would be classified in all clinical circumstances. The record's planning assumptions are described as illustrations rather than the trial's own design justification. Overall, the available registry information documents the intended study but is insufficient to judge comparative efficacy, safety, or statistical precision.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: RCT for Women With a Persisting Pregnancy of Unknown Location — NCT01800162.
• Registry record last updated 2017-12-29; status last verified 2017-12.
• Results first posted 2017-05-15.
• 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

NCT01800162 records a randomized, unmasked, parallel-group trial of three management strategies for women with a persisting pregnancy of unknown location: uterine evacuation followed by methotrexate for some, empiric methotrexate, and expectant management. Planned allocation was 2:2:1. The primary endpoint concerned clinical resolution within 6 weeks of randomization, described in the summary as an uneventful hCG decline to 5 IU/mL.

The record lists phase 1 and phase 2, enrollment of 2, and terminated status. It states that the study closed early, that data were not analyzed, and that patients were not followed for outcome. No primary or secondary outcome analysis is reported. Safety entries list zero serious adverse events, zero other adverse events, and zero deaths for the recorded uterine-evacuation and expectant-management groups; no methotrexate group entry is listed. The trial's comparative clinical question remains unanswered in the registry record.