Perioperative Administration of Tranexamic Acid for Placenta Previa and Accreta Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Perioperative Administration of Tranexamic Acid for Placenta Previa and Accreta Study (NCT02806024), a randomized phase 4 study. The primary outcome is Estimated Blood Loss (EBL).

2. Clinical Question

This is a question about a perioperative intervention and an estimated intraoperative blood-loss outcome. The posted outcome is a group mean, with a standard deviation for each arm; it is not a count of patients crossing a specified threshold for hemorrhage or transfusion. The registry also lists intraoperative blood transfusion units as a secondary outcome, but no secondary result is included in the posted results described in the record.

The question should be read as a comparison between TXA and placebo under the trial conditions described, not as a general comparison across all procedures or patient groups. The record does not report a formal eligibility definition beyond its description of patients with suspected or high-risk placenta accreta. It also does not report further details on how that risk was determined. Those details limit how specifically the study population can be characterized.

3. Trial Design

The registry identifies the study as phase 4 and completed, with a start date of 2016-11 and primary completion of 2018-07. Enrollment is listed as 14. The official title describes TAPPAS as a randomized, placebo-controlled double-blind trial, and the allocation is listed as randomized. The masking entry, however, is listed as triple. The record does not identify which specific roles were masked, so the difference between the title’s description and the masking entry cannot be resolved from the registry record.

The intervention descriptions specify two parallel treatment assignments: TXA and placebo. The TXA arm received 1 gram intravenously over 10 minutes immediately after infant delivery; the placebo arm received normal saline in a 50 cc bag immediately after delivery. The registry’s model entry says single-group, which does not align with the randomized allocation and the descriptions of treatment and placebo arms. The record does not explain this metadata difference. The posted primary outcome results are nevertheless presented separately for a treatment arm and a placebo arm.

For estimated blood loss, the treatment arm has 6 participants, with a mean of 3116.0 cc and a standard deviation of 3947.0. The placebo arm has 5 participants, with a mean of 9420.0 cc and a standard deviation of 12470. The enrollment entry is 14, while the group counts reported for this outcome are 6 and 5. The record does not explain the difference between the enrollment count and the outcome-group counts, or report why participants are not included in these posted outcome counts.

The registry describes the study as a pilot, but the specific design rationale, randomization procedures, allocation concealment methods, and sample-size justification are not reported in the registry record. The study’s completion status indicates a completed record, not that a definitive treatment effect or a conclusive between-arm analysis is available.

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: One patient was excluded from the study after consenting to participate, but before delivery. Two consented patients delivered at night, and were unable to be randomized.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Mean estimated blood loss (EBL) was calculated as below.

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 Estimated Blood Loss (EBL), measured over 1-3 hours (will be determined at the completion of the surgery)..

The primary endpoint is estimated blood loss (EBL), recorded in cc as a mean with a standard deviation. The description says the surgeon and anesthesia team estimate blood loss at the completion of surgery, including cesarean delivery and/or cesarean hysterectomy. Its stated timeframe is 1-3 hours, with the timing to be determined at the completion of surgery.

Blood loss is relevant to the study’s stated objective because the pilot is intended to examine whether TXA reduces blood loss during high-risk surgery related to placenta previa and placenta accreta. In general, an endpoint should reflect an outcome connected to the question a trial is designed to examine. An estimated blood-loss measure can describe the amount of blood loss observed during a procedure, while a mean summarizes the group’s central value and a standard deviation describes the spread of individual observations around that mean.

EBL is estimated by the clinical team rather than described as a directly measured quantity. That means the endpoint depends on the estimation process used at surgery completion. The registry does not report a detailed estimation protocol, whether the same procedure was used in every case, or whether estimates were assessed independently. These details matter when judging how consistently the endpoint was measured.

The posted outcome is continuous and is not a binary indicator of whether a patient experienced a particular event. The record does not define a threshold for clinically important blood loss. Nor does the primary outcome result, by itself, report transfusion, complications, or other clinical consequences. Intraoperative blood transfusion units are listed as a secondary outcome, but a result for that outcome is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: estimated blood loss in cc. The registry reports an arithmetic mean and standard deviation for each arm. In general, a mean gives a group-level average, while a standard deviation describes how dispersed observations are around that average. Neither statistic identifies the full distribution of outcomes, and neither alone quantifies uncertainty in a difference between groups.

What would a two-arm analysis estimate?

For a randomized comparison, an analysis of a continuous outcome would ordinarily estimate a contrast between the treatment and comparator groups, then quantify uncertainty around that contrast. The particular method depends on the analysis plan and features of the data. The registry record does not report the planned method, an estimated contrast, a standard error, a confidence interval, or a p-value for EBL. It explicitly indicates that a two-arm comparison for this continuous endpoint is missing or not estimable. Consequently, there is no inferential result to interpret, and none should be reconstructed from the group summaries as though it were the trial’s own analysis.

Why do the standard deviations matter?

In general, variability affects how precisely a group mean or a between-group contrast can be estimated. Greater spread in outcomes makes it harder to distinguish a group-level pattern from variation among participants. The posted standard deviations are 3947.0 for the TXA arm and 12470 for the placebo arm. These values describe within-arm spread, not the probability that a treatment effect is real, and not the uncertainty of a treatment contrast. They cannot substitute for an analysis that accounts for both group sizes and outcome variability.

Over-dispersion is a general concern when observations vary more than a simple model assumes. A model that does not represent the observed variability can produce uncertainty estimates that are too small or otherwise poorly calibrated. The registry does not report a model for EBL, a distributional assessment, or evidence that over-dispersion was evaluated. The summaries alone are insufficient to determine whether a particular model would be appropriate.

What can the means tell readers?

The treatment mean is 3116.0 cc and the placebo mean is 9420.0 cc. They provide descriptive information about the observed group summaries, but they do not show whether the apparent separation is compatible with chance variation under a specified model. An inferential test or interval would require a defined analysis and the relevant assumptions. No such result is posted. Avoid deriving a new effect estimate or uncertainty measure from these summaries and presenting it as a registry result.

In general, confidence intervals express a range of estimates compatible with the data and the assumptions of the method. A p-value, when reported, addresses compatibility with a specified null model; it does not measure the magnitude or clinical importance of an effect. Neither is available for the primary endpoint in this record. The standard deviations should not be mistaken for either kind of inferential statistic.

How should planning assumptions be read?

The record describes a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the original trial design or its sample-size justification. The calculated participant-per-arm planning estimates are not reported in the registry record. Such sample-size illustrations are prospective planning aids; they are not observed power and do not establish that the completed trial had a particular probability of detecting an effect.

In general, a normal approximation is a simplifying method for planning or inference. Its suitability depends on the data and design. With small groups and a continuous outcome, uncertainty can be sensitive to distributional assumptions, and a planning approximation should not be mistaken for a test of the observed trial results. The record does not report a detailed sample-size calculation, an assumed variance, or how the stated fraction of the observed effect was selected.

What is missing from the analysis record?

The registry reports zero analyses for the outcome record and does not provide a statistical analysis plan. It does not identify covariate adjustment, an approach to missing observations, a rule for handling extreme values, or a method for estimating the primary treatment contrast. Those elements are not reported in the registry record. Their absence means that the posted means and standard deviations should be read as descriptive summaries rather than evidence of a completed adjusted or unadjusted hypothesis test.

In general, statistical interpretation should distinguish observed data summaries, prespecified analysis methods, and exploratory calculations. The posted group summaries belong to the first category. A hypothetical analysis or planning illustration would not replace the trial’s own analysis, and no such two-arm EBL analysis is reported in the registry record. The main statistical conclusion is therefore about what is and is not estimable from the posted record: group summaries are present, but the comparative estimate and its precision are not.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Treatment Arm (Tranexamic Acid, or TXA)", "Placebo Arm")
n   <- c(6, 5)
m   <- c(3116, 9420)
sp  <- c(3947, 12474)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Treatment Arm (Tranexamic Acid, or TXA)  6  3116.000  3947.000  -1026.122  7258.122
CARM  Placebo Arm  5  9420.000  12474.000  -6068.517  24908.517

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies 1 secondary outcome: intraoperative blood transfusion, measured as the number of units transfused. The primary endpoint is estimated blood loss. No result for the secondary outcome is included in the posted results described in the record, and the registry lists 0 analyses.

When a study evaluates multiple outcomes or multiple statistical tests, multiplicity can arise. In general, testing several hypotheses can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry does not report whether multiplicity adjustment was planned or used, or how the primary and secondary outcomes were prioritized in an inferential analysis. This is not evidence that an adjustment was or was not necessary; the analysis details are not reported in the registry record.

The record does not report how missing outcome data were handled, whether any participants were excluded from the EBL analysis, or the reason the primary outcome counts are 6 and 5 while enrollment is listed as 14. It also does not identify an intention-to-treat population, a per-protocol population, or another analysis population. These omissions prevent assessment of whether the posted outcome groups represent all randomized participants or a subset selected by outcome availability.

In general, missing-data methods rely on assumptions about why outcomes are unavailable. Without counts and reasons for missingness or a stated analytic approach, the effect of missing observations on the comparison cannot be assessed. The record likewise does not report sensitivity analyses. Accordingly, neither the handling of missing data nor the population used for an inferential analysis can be reconstructed from the posted summaries.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dvt / pe (0.0%).

The registry reports serious adverse events for 0 of 6 participants in the TXA arm and 0 of 5 participants in the placebo arm. Deaths are reported as 0 in each arm. The serious adverse event term DVT / PE is listed as 0.0%. These are the safety counts recorded for the groups and outcome record; they are not evidence that serious events are impossible or that the treatments have equivalent safety.

Other adverse events are reported for 4 of 6 participants in the TXA arm and 3 of 5 participants in the placebo arm. The record does not give further event descriptions in the registry record for this outcome, nor does it state whether these events were judged related to study treatment. Serious and other adverse events are distinct categories in the record and should not be combined.

In general, zero observed events in a small group do not establish zero underlying risk. Sparse safety counts provide limited information about uncommon events, and group counts alone do not show event timing, severity details, or causality. The registry does not report a comparative safety analysis or uncertainty intervals for these counts. Interpret them as event counts in the reported groups, not as a formal demonstration of safety or a treatment effect.

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

The record documents a randomized, placebo-controlled pilot study and posts mean estimated blood loss for the TXA and placebo groups. The means are 3116.0 cc and 9420.0 cc, respectively, with standard deviations of 3947.0 and 12470. These figures describe the observed groups. They do not establish that TXA caused a difference in blood loss, because no valid two-arm analysis or measure of uncertainty is reported for the primary endpoint.

The findings also do not establish that the treatments are equivalent. A lack of a posted inferential result is not the same as evidence of no effect. Without an estimated contrast and its precision, the record cannot show which range of comparative effects is compatible with the data. The standard deviations describe variability within the groups and should not be read as uncertainty intervals for the treatment comparison.

The outcome is an estimate made by the surgical and anesthesia teams at completion of the procedure. It is relevant to the stated blood-loss question, but the registry does not provide details about how the estimate was standardized or assessed. The result therefore speaks to the recorded EBL summaries, not necessarily to every aspect of blood loss or related outcomes. Transfusion units are listed as a secondary outcome, but a result is not reported in the registry record.

The posted group counts are 6 and 5, while enrollment is listed as 14. The record does not explain the difference. It also does not report the analysis population or missing-data handling. These gaps make it difficult to judge how representative the posted summaries are of the randomized participants.

As a pilot, the study may offer descriptive information about a high-risk surgical setting, but the posted results do not support a definitive comparative conclusion. The appropriate interpretation is bounded: the registry reports group-level EBL summaries and limited safety counts, while the size, precision, and robustness of any treatment effect remain unresolved in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it poses a randomized comparison in a specialized, high-risk surgical context while reporting a continuous endpoint with substantial uncertainty left unquantified. Estimated blood loss is presented as a mean and standard deviation, which makes the group summaries easy to identify but does not complete the statistical comparison. Readers need a treatment contrast and a measure of its precision to assess what the randomized data say about the primary question.

The outcome-group counts are small, and the record lists enrollment as 14 while posting EBL results for groups of 6 and 5. Differences between enrolled and analyzed counts can affect interpretation, especially when the reasons for outcome availability are unknown. Here, those reasons and the analysis population are not reported. That limits evaluation of the representativeness of the summaries and of possible missing-data bias.

The record also illustrates why metadata and analysis reporting matter. Allocation is listed as randomized and the arms are described as TXA and placebo, but the model entry says single-group. The official title says double blind while the masking entry says triple. These descriptions do not have to invalidate the reported summaries, but the registry does not explain them, leaving aspects of the design unclear.

Finally, a pilot result and a planning illustration serve different purposes. Planning assumptions based on an observed effect do not establish observed power, and they do not substitute for an analysis of the trial outcome. Without the comparative estimate, uncertainty interval, and analysis details, the posted means are informative as descriptive summaries but limited as evidence about a treatment effect. Clear reporting of the analysis and participant flow would be important for interpreting this trial’s statistical contribution.

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 interpreting the result is that the registry reports group means and standard deviations but no two-arm analysis for EBL. The record states that values are missing or not estimable for a continuous two-arm comparison. No effect estimate, confidence interval, p-value, or analysis method is reported. The descriptive means therefore cannot support an inferential conclusion about the treatment contrast.

The EBL outcome counts are 6 in the TXA arm and 5 in the placebo arm, while enrollment is listed as 14. The registry does not explain the count difference or identify the analysis population. It also does not report whether outcomes were unavailable, participants were excluded, or another process led to the posted counts. This limits assessment of selection and missing-data concerns.

The endpoint is estimated by the surgeon and anesthesia team. The record does not report a detailed measurement protocol or how consistency of estimation was addressed. It also does not report individual outcome values or a distributional analysis. As a result, the impact of variability or unusual observations cannot be assessed from the group summaries.

There are design-description ambiguities: the allocation entry is randomized and the arm descriptions identify treatment and placebo, but the model entry says single-group; the title describes double blinding while masking is listed as triple. The record does not resolve these differences or identify masked roles. It likewise does not report randomization procedures, allocation concealment, a statistical analysis plan, multiplicity handling, or a missing-data strategy.

Finally, the registry lists intraoperative transfusion units as a secondary outcome but does not report its result in the posted record. Safety counts are limited to the reported groups and do not include a comparative safety analysis. Together, these gaps constrain interpretation of both efficacy-related and safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Perioperative Administration of Tranexamic Acid for Placenta Previa and Accreta Study — NCT02806024.
• Registry record last updated 2019-12-03; status last verified 2019-11.
• Results first posted 2019-12-03.
• 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.

19. Record Summary

NCT02806024 is the completed phase 4 TAPPAS study, described as a randomized, placebo-controlled trial of perioperative tranexamic acid for patients with suspected or high-risk placenta accreta undergoing cesarean delivery, with or without cesarean hysterectomy. The TXA description specifies 1 gram intravenously over 10 minutes immediately after delivery; the comparator is normal saline in a 50 cc bag.

The primary outcome is estimated blood loss in cc, assessed by the surgeon and anesthesia team at completion of surgery. The treatment group has 6 participants, a mean of 3116.0 cc, and a standard deviation of 3947.0. The placebo group has 5 participants, a mean of 9420.0 cc, and a standard deviation of 12470. No valid two-arm analysis of this continuous endpoint is reported. Intraoperative transfusion units are listed as a secondary outcome, but a result is not reported in the registry record.

The record lists enrollment as 14 and does not explain the difference from the EBL group counts. It also does not report the analysis population, missing-data handling, or a statistical analysis plan. The posted primary outcome summaries are therefore descriptive, and the comparative effect and its precision remain unresolved.