Oral Progesterone and Low Dose Aspirin in the Prevention of Preeclampsia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Progesterone and Low Dose Aspirin in the Prevention of Preeclampsia (NCT00719537), a randomized na study. The primary outcome is Incidence of Preeclampsia.

2. Clinical Question

3. Trial Design

The registry record describes a prospective, randomized clinical trial with a parallel design and quadruple masking. It lists the study phase as not applicable. The study was terminated, and the recorded enrollment was 3. The sponsor is John Uckele. The record lists a start in 2008-07 and primary completion in 2011-03.

The two arms shared aspirin treatment. Participants assigned to the control arm were described as receiving aspirin 81 mg orally once per day and a placebo oral tablet once a day. Participants assigned to the other arm were described as receiving aspirin 81mg orally once per day and progesterone 200mg once a day. The registry record does not report additional details about the duration of treatment, adherence assessment, allocation concealment, the methods used to implement masking, or the reasons the trial was terminated.

The design aimed to isolate the contrast associated with progesterone by using a placebo in the comparison arm while keeping aspirin common to both arms. Randomization can support a causal comparison when the trial is sufficiently complete and the analysis preserves the randomized groups, but the posted results are too sparse for that comparison. The registry record gives no formal results analysis, and the primary endpoint has no reported participant count in the progesterone arm. The available information therefore describes the intended design more clearly than it establishes what happened across the randomized groups.

The study population was narrowly defined by prior preeclampsia, and the primary outcome concerned preeclampsia during the second and third trimester of pregnancy. The registry record does not report eligibility criteria beyond the history described in the title and summary, nor does it specify additional population characteristics. Details of a protocol, sample-size justification, interim analyses, and a prespecified statistical plan are not reported in the registry record.

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: 1 Participant withdrawn in aspirin and placebo group, one participant lost to followup in aspirin and progesterone group.

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 Incidence of Preeclampsia, measured over second and third trimester of pregnancy.

The primary endpoint was the incidence of preeclampsia, expressed as the number of participants with preeclampsia in the second and third trimester of pregnancy. It is a binary participant-level outcome: each participant either met the outcome definition during the stated period or did not. The posted value in the aspirin-and-placebo arm is 0 participants with preeclampsia among 1 participant reported for the endpoint. In the aspirin-and-progesterone arm, 0 participants are reported for the endpoint and no outcome value is available.

This endpoint was relevant to the stated prevention question because it records whether the condition occurred during a defined part of pregnancy. A participant count is easy to interpret as an event count, but comparing counts across randomized arms requires outcome information from participants in both arms. With no reported endpoint participants in the progesterone arm, the registry data cannot establish the frequency of the event in that arm or estimate a meaningful treatment contrast.

The endpoint description does not report diagnostic criteria, independent adjudication, or other detail about how preeclampsia was identified. The registry record also notes one participant withdrawn in the aspirin-and-placebo group and one participant lost to follow-up in the aspirin-and-progesterone group. Those notes matter because outcome ascertainment may be incomplete when participants withdraw or cannot be followed. How those participants were handled in the endpoint count is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record reports a binary primary endpoint: the count of participants with preeclampsia in the second and third trimester of pregnancy. The posted endpoint data are 0 among 1 participant for aspirin and placebo, and no reported participants or endpoint value for aspirin and progesterone. There are no posted analyses. The methods that would ordinarily be used to compare binary outcomes therefore cannot produce a defensible treatment-effect estimate from the information recorded.

What a binary outcome comparison needs

For a randomized two-arm comparison of a binary outcome, the analysis needs both the number of participants with the event and the number of participants assessed in each arm. Those counts permit the event frequency to be estimated within each arm and the difference between arms to be described. Here, one arm has only a single participant reported and the other arm has no participants reported for the endpoint. A missing arm result cannot be interpreted as zero events or used as a complete denominator. Accordingly, an arm-to-arm risk contrast is not estimable from these entries.

General statistical explanation: with sparse binary data, the observed counts contain little information about the underlying event rates. Standard methods may behave poorly when counts are extremely small or an outcome cell is empty. Alternative exact or penalized methods can address some sparse-data problems in a suitably documented analysis, but they cannot create missing participant outcomes or resolve uncertainty about who was assessed. The registry record does not identify a method chosen for this endpoint.

Effect estimates and confidence intervals

A treatment-effect estimate summarizes the contrast between the randomized strategies on a defined scale, such as a difference in event probabilities or a relative measure. A confidence interval communicates uncertainty around an estimate under the assumptions of the chosen method. General statistical explanation: a narrow interval indicates greater precision, while a wide interval indicates substantial uncertainty. Neither an estimate nor an interval is reported for this trial. Because the progesterone arm has no endpoint participants in the posted results, it would be misleading to construct a numerical comparison from the available entries.

A p-value, when reported, addresses how compatible the observed data are with a specified null model under the test assumptions. It does not measure the probability that a treatment works, and it does not describe the size or clinical importance of an effect. No p-value or hypothesis test is posted. The record also does not report a statistical analysis plan, so the intended estimand, analysis method, and handling of missing outcomes are not known.

Why over-dispersion is not the main issue

General statistical explanation: over-dispersion describes variability greater than a statistical model expects, often requiring a model that allows extra variation. It is relevant to some count and clustered data analyses. The primary endpoint in this record is a participant count for a binary event, and no dispersion estimate is reported. The immediate limitation is not an estimate of over-dispersion; it is the absence of usable outcome information for one arm and the tiny reported count in the other. No over-dispersion adjustment is described in the registry record.

Randomization and the analysis population

Random assignment is intended to make treatment groups comparable at the outset, on average. A treatment comparison usually aims to preserve that randomized assignment in the analysis, because excluding participants after randomization can undermine the balance created by randomization. The registry record does not state whether the primary analysis was intended to include all randomized participants, only participants who received treatment, or another population. It also does not describe how the withdrawn participant or the participant lost to follow-up was handled. The posted endpoint counts cannot establish the analysis population.

General statistical explanation: missing outcome data can bias an estimate when the probability of being observed is related to outcome status or treatment assignment. Even when missingness does not create bias, fewer observed outcomes reduce precision. Investigators may use prespecified approaches such as sensitivity analyses to examine assumptions about missing outcomes, but those approaches depend on participant-level information and an analysis plan. Neither a missing-data method nor such sensitivity analyses are reported in the registry record.

Interpreting planning calculations

The registry record describes planning illustrations as based on an observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated output convention is participants per arm. These are planning assumptions, not a report of the trial's design rationale, and such calculated sample sizes are not observed power. The registry record does not report the study's own sample-size justification.

General statistical explanation: sample-size planning estimates how much information a future study might need to detect a chosen effect under specified assumptions. The result depends on the assumed event frequency, effect size, allocation, analysis method, and desired operating characteristics. If the effect used as the planning anchor is not estimable, the resulting illustration has no dependable empirical basis. The current endpoint counts do not supply a stable two-arm observed effect for such planning. A planning illustration cannot compensate for sparse data or stand in for evidence about the effect in this trial.

Other statistical details are absent. The registry record does not report an interim-analysis plan, multiplicity adjustment, prespecified covariates, subgroup analyses, model diagnostics, or an approach to protocol deviations. There is no posted analysis result against which to assess whether the intended method was followed. The appropriate statistical reading is therefore descriptive: a primary outcome count is recorded for one arm, no endpoint participants are recorded for the other, and a comparative analysis is unavailable.

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("Aspirin and Placebo")
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  Aspirin and Placebo  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study tests several outcomes, time points, subgroups, or treatment contrasts. Repeated testing can increase the chance of finding an apparently notable result by chance, so a statistical plan may specify which outcome is primary and whether adjustments are needed. The registry record lists one outcome measure and no secondary outcome results. It does not report a multiplicity strategy or an analysis plan. With no formal analysis posted, there are no reported hypothesis tests to evaluate for multiplicity.

Missing data are a more immediate concern. The primary outcome population note states that one participant was withdrawn in the aspirin-and-placebo group and one participant was lost to follow-up in the aspirin-and-progesterone group. The posted endpoint lists one participant for the aspirin-and-placebo arm and none for the aspirin-and-progesterone arm. The record does not explain how the withdrawal and loss to follow-up relate to those endpoint counts, whether these were the only missing outcomes, or how missing values were handled.

The registry record does not report whether the analysis followed an intention-to-treat principle, used another analysis population, or included sensitivity analyses for missing outcomes. It also does not describe a missing-data assumption. These omissions prevent assessment of whether the reported endpoint counts represent all randomized participants or a selected subset. The randomized allocation and the analyzed endpoint population should not be assumed to be identical.

No interim analysis, stopping rule, or multiplicity adjustment is reported in the registry record. The terminated status is recorded, but its reason and relationship to any planned analyses are not reported. These gaps do not establish that a particular practice was absent; they mean its use is not documented in the registry record.

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 1% reporting threshold.

The serious adverse event entries report 0 affected among 2 at risk in the aspirin-and-placebo group and 0 affected among 1 at risk in the aspirin-and-progesterone group. The deaths field is 0 in both groups. The other adverse event entries also report 0 affected among 2 at risk in the aspirin-and-placebo group and 0 affected among 1 at risk in the aspirin-and-progesterone group. No serious adverse event terms are listed.

These are small at-risk counts, so the absence of recorded events does not establish that the groups have identical safety profiles or that uncommon events could not occur. General statistical explanation: when few participants are observed, even a count of zero leaves substantial uncertainty about the event rate that might be seen in a larger population. A risk estimate and uncertainty interval are not reported for these entries.

The adverse event denominators differ from the primary endpoint counts and from total enrollment. The registry record does not explain the populations used for these safety summaries, the observation period, or how adverse events were collected and classified. The figures should therefore be read narrowly as the event counts recorded for the listed at-risk groups, rather than as a complete comparative safety analysis. They do not support medical advice or a broad conclusion about safety.

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

The registry record establishes that a randomized, parallel trial was intended to compare aspirin with progesterone against aspirin with placebo in pregnant patients with a prior history of preeclampsia. The primary endpoint was preeclampsia during the second and third trimester. The posted primary outcome includes 0 participants with the event among 1 participant reported in the aspirin-and-placebo arm. The aspirin-and-progesterone arm has no participants reported for that endpoint and no event count.

These data do not show whether adding progesterone changes the incidence of preeclampsia. There is no estimable two-arm comparison, no effect estimate, no confidence interval, and no formal statistical analysis. The absence of an event count in one arm is not evidence of no events in that arm. Likewise, 0 events among the one participant reported in the other arm is not sufficient to establish a dependable event frequency for that treatment strategy.

The trial's enrollment was 3 and its status is terminated. The record also notes one withdrawal in the aspirin-and-placebo group and one loss to follow-up in the aspirin-and-progesterone group. The relationship between these participant dispositions and the endpoint denominators is not reported. The reason for termination, intended enrollment, and sample-size justification are also not reported in the registry record.

As a result, these entries are best understood as a limited registry record rather than as a completed comparative estimate. They cannot establish equivalence, demonstrate benefit, or rule out an effect in either direction. The small amount of posted outcome information and the missing analysis are the main reasons no inference about the relative efficacy of the regimens can be drawn.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a randomized design and an informative randomized comparison. Randomization specifies how treatment assignment is intended to occur; it does not guarantee that enough participants will contribute outcome data to estimate a treatment contrast. Here, the registry records randomized allocation but only one participant in one arm and none in the other for the primary endpoint.

It also illustrates why denominators matter. An event count without a clear denominator is not an event rate, and a missing outcome count cannot be read as zero events. The endpoint population note includes a withdrawal and a loss to follow-up, while the posted endpoint counts do not explain the disposition of all enrolled participants. Statistical interpretation depends on knowing who was followed and how missing outcomes were handled.

The record is also a reminder that a trial's status and the results available from it answer different questions. Termination is recorded, but the reason is not. A formal analysis is not posted, and the outcome data do not yield a two-arm estimate. Consequently, neither a nominal effect nor a conclusion of no difference can be inferred from these results.

Finally, planning calculations depend on reliable inputs. An observed effect from an extremely sparse, incomplete comparison is not a sound foundation for future sample-size assumptions. This case makes the limitations of planning illustrations clear: assumptions can describe a calculation, but cannot supply missing empirical information or replace a trial's own design rationale.

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 most important trial-specific limitation is the extremely limited primary outcome information. The registry reports one participant for the aspirin-and-placebo endpoint and none for the aspirin-and-progesterone endpoint. This prevents estimation of an outcome contrast and leaves the event status of participants without reported endpoint data unresolved.

Enrollment was 3, while the primary outcome note records one withdrawal in the aspirin-and-placebo group and one participant lost to follow-up in the aspirin-and-progesterone group. The record does not provide a flow of participants from enrollment through allocation, follow-up, and analysis. It also does not explain whether other participants were excluded, or how the endpoint counts were derived from the dispositions described.

The trial is marked terminated, but the reason for termination and whether it was related to recruitment, feasibility, safety, or another issue are not reported in the registry record. The intended sample size and the trial's sample-size justification are not reported. The record does not include a formal statistical analysis, an estimate with uncertainty, or a statistical plan that would clarify the intended analysis population and handling of missing outcomes.

Important endpoint details are also not described, including the diagnostic criteria used for preeclampsia and any process for confirming outcome status. The record does not report treatment duration, adherence, detailed eligibility criteria, participant characteristics, or additional follow-up information. The safety summaries involve very small at-risk groups, and the record does not describe their observation periods or collection methods. Together, these limitations mean the posted results are insufficient for a reliable efficacy comparison or a broad safety assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Oral Progesterone and Low Dose Aspirin in the Prevention of Preeclampsia — NCT00719537.
• Registry record last updated 2017-04-17; status last verified 2017-03.
• Results first posted 2017-04-17.
• 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 record describes a terminated, randomized, quadruple-masked, parallel trial of aspirin with progesterone versus aspirin with placebo in pregnant patients with a prior history of preeclampsia. Enrollment was 3. The primary outcome was the number of participants with preeclampsia in the second and third trimester of pregnancy.

The posted primary outcome reports 0 events among 1 participant in the aspirin-and-placebo arm and no participants or outcome value in the aspirin-and-progesterone arm. One participant was withdrawn in the placebo arm and one was lost to follow-up in the progesterone arm. No formal analysis or two-arm comparison is reported. The available outcome data do not support an estimate of the treatment contrast.

The registry record does not report the reason for termination, the study's sample-size justification, a statistical plan, or the handling of missing outcomes. Safety summaries record no serious adverse events or deaths in the small groups listed, but do not support broad comparative conclusions.