Study of the Efficacy and Safety of AMAG-423 (Digoxin Immune Fab) in Antepartum Subjects With Severe Preeclampsia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Efficacy and Safety of AMAG-423 (Digoxin Immune Fab) in Antepartum Subjects With Severe Preeclampsia (NCT03008616), a randomized phase 2, phase 3 study. The primary outcome is Proportion of Infants Who Have Severe IVH, NEC, or Death by 36 Weeks Corrected Gestational Age.

2. Clinical Question

The clinical question is whether the study intervention, when used in this setting, is associated with a different frequency of the infant composite outcome than placebo. The endpoint combines three possible outcomes: severe IVH, NEC, or death by the stated age. A composite can capture more than one type of outcome, but its interpretation depends on the definitions of each component and the way events are counted. Those details are not reported in the registry record.

The listed secondary outcomes are change from baseline in serum creatinine and incidence of pulmonary edema. Their analysis results are not reported in the registry record. The primary endpoint is described in terms of infants, while the trial population is described as antepartum subjects with severe preeclampsia. The registry record does not report the planned analysis population, the method for connecting infant outcomes to study participants, or whether all components were assessed in the same way.

3. Trial Design

The registry describes a Phase 2b/3a, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Its phase fields identify Phase 2 and Phase 3. The reported allocation was randomized, the masking was quadruple, and the model was parallel-group. These design features describe the intended comparison: participants were allocated to AMAG-423 or placebo, with masking intended to limit knowledge of assignment among designated parties. The registry does not report further details about the randomization procedure or which parties were masked.

The study evaluated AMAG-423, identified as digoxin immune Fab, in addition to expectant management, compared with placebo. The AMAG-423 regimen was 3.2 mg/kg by intravenous infusion over 30 minutes every 6 hours for 4 days. The placebo regimen was normal saline by intravenous infusion over 30 minutes every 6 hours for 4 days. The registry does not report additional details about the expectant management approach or how it was standardized between groups.

Enrollment was 58. The study started on 2017-04-12, and the primary completion date is listed as 2020-08-13. Its status is terminated. The registry record does not report the reason for termination, whether termination occurred before or after the planned enrollment was reached, or whether the primary completion date reflects completion of follow-up for all enrolled participants.

The listed primary endpoint is an infant outcome assessed by 36 weeks corrected gestational age. Secondary outcomes are change from baseline in serum creatinine and incidence of pulmonary edema. The registry record lists three outcome measures but zero analyses. It does not report a statistical analysis plan, the number of participants assigned to each group for the primary analysis, or the analysis populations. These omissions limit interpretation of the study's intended and completed comparisons.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Infants Who Have Severe IVH, NEC, or Death by 36 Weeks Corrected Gestational Age, measured over 36 weeks corrected gestational age.

The primary endpoint is the proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age. It is a composite endpoint: an infant qualifies by experiencing at least one of the listed outcomes by the specified assessment age. The registry record does not report operational definitions for severe IVH or NEC, how events were adjudicated, how infants with more than one component event were handled, or the denominator used to calculate the proportion.

In general, a composite endpoint can represent several clinically important outcomes in one measure and may capture a broader range of events than any single component. It can also be difficult to interpret if the components differ in severity or frequency. An overall composite result does not by itself show which component contributed to a difference between groups. Component-specific counts and estimates are needed for that interpretation; they are not reported in the registry record.

The endpoint is stated in terms of infants, whereas the trial population is described as antepartum subjects with severe preeclampsia. The registry record does not report details of the planned infant-level analysis, including whether outcomes were linked to each enrolled subject, how multiple infants related to one subject would be handled, or how missing infant assessments would be treated. Without a reported comparison, event counts, and analysis details, the endpoint definition alone does not establish an observed treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on what was measured, how participants were assigned, which observations were included, and how uncertainty was quantified. The registry record gives some design information, but does not report an analysis plan or results for the primary endpoint. The explanations below describe general statistical concepts and distinguish them from methods documented for this trial.

What does randomization contribute?

In general, randomization assigns participants to study groups by a chance-based process. If implemented as planned, it can reduce systematic differences between groups at the point of assignment, making the comparison more interpretable. It does not guarantee that groups will be identical, particularly in a study with limited enrollment. The registry record identifies the study as randomized but does not report the sequence-generation method, allocation concealment details, stratification factors, or procedures used to maintain assignments.

What does masking mean?

The registry lists quadruple masking. In general, masking is intended to reduce the influence of knowledge about treatment assignment on care, reporting, assessment, or analysis. The label alone does not identify which four parties were masked or whether masking was maintained throughout the study. Those details are not reported in the registry record. The infusion schedules were described for both groups, but the registry record does not report whether the placebo was designed to match other features of the active infusion.

How should a composite endpoint be read?

The primary measure combines severe IVH, NEC, or death by 36 weeks corrected gestational age. In general, a composite endpoint treats occurrence of any listed component as meeting the outcome definition. This can make the endpoint capture a wider range of events, but an overall result does not explain whether one component or several components account for the observed pattern. Component definitions, event counts, and any hierarchy for components would be needed to examine those questions. They are not reported in the registry record.

The endpoint is expressed as a proportion, which generally requires a defined numerator and denominator. The numerator depends on the count of infants meeting the endpoint definition; the denominator depends on which infants are included in the analysis. The registry record does not report those values, the analysis population, or the approach to infants with incomplete follow-up. It also does not report how the infant endpoint was associated with the antepartum subjects enrolled in the study.

What do confidence intervals and p-values describe?

In general, a confidence interval describes the range of values reasonably compatible with an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. A p-value describes how compatible the observed data are with a specified null model, assuming that model and the analysis assumptions are appropriate. Neither quantity, by itself, establishes clinical importance or proves that a treatment caused an outcome.

No primary endpoint estimate, confidence interval, or p-value is reported in the registry record. The lack of these results means the magnitude and precision of any group difference cannot be evaluated. A statement that no analysis is listed is not equivalent to a finding of no difference; it means that the registry record does not present an analysis from which such a finding could be assessed.

How do sample-size illustrations differ from trial results?

In general, a sample-size calculation is a planning tool that estimates how many observations may be needed for a specified design and assumed effect. It is not an observed result and does not describe the probability that the completed trial demonstrated an effect. The planning framework associated with this study uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. The registry record does not report the trial's own sample-size justification or the assumptions used in its original design.

Any sample-size illustrations should be understood as planning exercises rather than observed power. They do not replace a reported treatment estimate with uncertainty bounds, and they cannot resolve the absence of a primary endpoint analysis. The record does not report whether interim analyses were planned or conducted, or whether any changes were made to the statistical plan.

Why can count outcomes require care?

In general, counts may be analyzed using methods that account for their distribution and variability. If count data vary more than a simple model expects, over-dispersion can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. This is a general consideration, not a method documented for this trial. The primary endpoint is described as a proportion of infants, and the registry record does not report the statistical model, variance assumptions, or any adjustment for clustering or repeated observations.

The record reports serious adverse event counts by group, but does not provide a statistical analysis of those counts. Descriptive counts can be informative about what was recorded, but they do not by themselves quantify the precision of a between-group comparison. No adjusted or unadjusted safety comparison is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was addressed. Multiplicity arises when several outcomes, comparisons, time points, or analyses are considered: the more opportunities there are to detect an apparent difference, the more important it is to understand whether and how the analysis controlled the chance of false-positive findings. The record lists a primary endpoint and secondary outcomes, but does not report a hierarchy of testing, an adjustment procedure, or whether secondary outcomes were intended to be confirmatory or exploratory.

The registry lists three outcome measures and zero analyses. It does not report results for the primary endpoint or the listed secondary outcomes. Therefore, there are no reported outcome-specific estimates to evaluate for multiplicity, and the absence of a reported analysis should not be read as a negative result.

Missing-data methods are also not reported in the registry record. For the infant endpoint, the record does not state how missing assessments, loss to follow-up, or incomplete outcome information would be handled. It does not report whether the analysis would include all randomized participants or another defined population. The analysis populations for the serum creatinine and pulmonary edema outcomes are also not reported.

In general, missingness can affect interpretation when the probability of an outcome being observed is related to treatment assignment or the outcome itself. Analysis choices may include assumptions about missing observations, but those assumptions and any sensitivity analyses are not reported for this study. The registry record also does not report whether analyses were adjusted for baseline characteristics or other covariates. Without a stated statistical plan, analysis population, and missing-data approach, it is not possible to determine how the listed outcomes were intended to be tested or how robust any estimates would have been.

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 serious adverse event terms

Serious events with the highest arm-level rate: nasal congestion (7.1%), rash (7.1%), vomiting (6.9%), nausea (3.6%), fatigue (3.6%).

The registry reports serious adverse events for 15 of 28 at risk in the AMAG-423 group and 8 of 29 at risk in the placebo group. It reports zero other adverse events in each group and zero deaths in each group under the listed safety fields. These figures describe what the registry records for the groups; they are not, by themselves, a statistical comparison or evidence that an observed difference is reliable.

The registry also lists serious adverse event terms with percentages: nasal congestion and rash at 7.1%, vomiting at 6.9%, and nausea, fatigue, and respiratory tract infection at 3.6% each. The record does not report arm-specific denominators for these term percentages, so they cannot be attributed to a specific group based on the available information. It does not provide event-level narratives, timing, severity grades, or details about recurrence.

In general, safety counts are interpreted in light of the population assessed, duration of observation, event definitions, and completeness of reporting. Those details are not fully reported in the registry record. A count of zero in a listed field does not establish that no event of any kind occurred; it describes the field as recorded. No inferential comparison or uncertainty interval for these safety counts is reported.

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

The registry supports a clear description of the study question and design: it evaluated AMAG-423 alongside expectant management against placebo alongside expectant management in antepartum subjects with severe preeclampsia. It was randomized, quadruple-masked, and parallel-group, and the listed primary endpoint concerned an infant composite by 36 weeks corrected gestational age. The study is marked terminated.

The registry record does not report a primary endpoint analysis. It gives no group-specific infant counts for severe IVH, NEC, or death; no estimate comparing the groups; and no confidence interval or p-value. It is therefore not possible to characterize the direction, size, or precision of the primary comparison from this record. The absence of reported results does not show that the groups were the same, and it does not show that one group had better outcomes.

The reported serious adverse event counts are descriptive: 15 of 28 at risk in the AMAG-423 group and 8 of 29 at risk in the placebo group. The registry lists zero other adverse events and zero deaths for each group in the corresponding fields. These entries do not establish a causal effect or a statistically reliable safety difference. The record does not report an inferential comparison, event-level details, or the reason the study was terminated.

In general, conclusions about a treatment comparison require an estimate, its uncertainty, and enough detail to judge the analysis and data completeness. Such information is not reported for the primary endpoint. The findings should therefore be read as a registry description of the study and selected safety reporting, not as a completed statistical assessment of efficacy or as evidence for a clinical decision.

13. Why This Trial Matters Statistically

This trial is statistically notable because the registry describes a randomized, masked comparison but does not report analyses of its primary endpoint. Randomization can support a more interpretable comparison when properly implemented, yet the design alone cannot establish what the study found. Without outcome counts and an estimate with its uncertainty, readers cannot assess the size or precision of a difference in the infant composite.

The endpoint also raises an important analysis question: the study population is described as antepartum subjects with severe preeclampsia, while the primary outcome is expressed as a proportion of infants. The registry does not report the planned analysis population or how infant outcomes were linked to enrolled subjects. These details matter to the denominator, the handling of more than one infant per subject if applicable, and the assumptions used for inference. The record does not report the relevant procedures.

Termination is another reason to distinguish study status from study findings. The registry marks the trial terminated, but does not report why it ended. That status does not establish whether the reason was scientific, operational, or otherwise, and it does not substitute for endpoint results.

The safety entries illustrate the difference between descriptive reporting and a comparative analysis. Counts by group are available, but no uncertainty estimates or statistical comparison are reported. Overall, the record allows readers to identify the question, intervention, comparator, and selected safety counts while making clear how much statistical information is unavailable. That distinction is essential: a randomized design is a framework for inference, not itself a result.

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.

Several trial-specific limitations restrict interpretation of the registry record. The study is marked terminated, but the reason for termination is not reported in the registry record. It is also not reported whether the primary completion date represents completion of follow-up for all enrolled participants or how termination affected the planned analyses.

The primary endpoint concerns infants, whereas the listed study population is antepartum subjects with severe preeclampsia. The registry record does not explain the planned unit of analysis, the relationship between infants and enrolled subjects, or how the endpoint denominator was defined. It does not provide component definitions for severe IVH or NEC, event counts, or the approach to infants with multiple component outcomes.

No primary or secondary outcome analyses are reported. The registry does not report the statistical analysis plan, analysis populations, missing-data procedures, multiplicity approach, interim analyses, or covariate adjustments. It does not report the protocol's sample-size justification. These omissions prevent assessment of whether the planned methods were followed and how much uncertainty would surround any result.

Safety reporting is also limited. Serious adverse event counts are listed by group, but event-level descriptions, timing, duration of observation, and statistical comparisons are not reported. The listed serious-event term percentages do not include arm-specific denominators in the record. The reported zero counts for other adverse events and deaths should be understood as entries in the registry's safety fields, not as proof that no other clinical events occurred.

Finally, the registry record does not report detailed participant characteristics or the allocation procedures. These limitations are specific to the information available for this trial and should be considered alongside the absence of a primary endpoint analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of the Efficacy and Safety of AMAG-423 (Digoxin Immune Fab) in Antepartum Subjects With Severe Preeclampsia — NCT03008616.
• Registry record last updated 2026-05-22; status last verified 2024-08.
• Results first posted 2026-05-22.
• 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

NCT03008616 is a terminated randomized, quadruple-masked, parallel-group study of AMAG-423 (digoxin immune Fab) versus placebo, both alongside expectant management, in antepartum subjects with severe preeclampsia. It is described as Phase 2b/3a and has Phase 2 and Phase 3 phase fields. Enrollment was 58; the study started on 2017-04-12, with primary completion listed as 2020-08-13.

The primary endpoint is the proportion of infants with severe IVH, NEC, or death by 36 weeks corrected gestational age. Secondary outcomes are change from baseline in serum creatinine and incidence of pulmonary edema. The registry lists zero analyses, and primary endpoint results are not reported in the registry record.

Serious adverse event counts are 15 of 28 at risk for AMAG-423 and 8 of 29 at risk for placebo. The registry lists zero other adverse events and zero deaths in each group. It does not report the reason for termination or a statistical analysis plan.