Fetoscopic NEOX Cord 1K® Spina Bifida Repair: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fetoscopic NEOX Cord 1K® Spina Bifida Repair (NCT04243889), a na na study. The primary outcome is Number of Pregnant Women With Successful Fetoscopic Repair of the Defect Using NEOX Cord 1K®.

2. Clinical Question

The clinical question centers on whether the defect appears successfully closed immediately after the procedure. The proposed rationale is to create a watertight covering and thereby decrease postnatal morbidities, but the primary endpoint is a procedural assessment, not a direct measure of later morbidity. The primary endpoint is defined as a count of participants with successful repair, rather than a comparison of outcomes between treatment groups.

The registry record lists spina bifida, myelomeningocele, and myeloschisis as conditions. It describes patients intending to undergo open in-utero repair as being offered screening for an alternative minimally invasive approach. The record does not establish a comparison between fetoscopic repair and open repair; all eligible fetuses within the trial are described as receiving NEOX Cord 1K®. Specific criteria for screening and eligibility are not reported in the registry record.

3. Trial Design

The registry describes a single-group interventional study of fetoscopic spina bifida repair using NEOX Cord 1K®. The listed intervention is a device, and the arm is titled NEOX Cord 1K applied fetoscopically. Allocation is recorded as NA, and the trial is not a randomized comparison. There is no like-for-like control arm in the record, so the design does not support a direct within-trial comparison of the graft with another repair approach.

The record lists enrollment as 100. It does not clarify in the information available whether this figure represents a planned target or the number ultimately enrolled. The study began on 2020-08-28, has a primary completion date of 2023-05-30, and is listed as active, not recruiting. The phase is listed as NA. The sponsor is The University of Texas Health Science Center, Houston.

Masking is listed as NONE. Separately, the primary endpoint description says that images are sent to 3 independent blinded neurosurgeons for review. These statements concern different parts of the record: the trial-level masking entry and the stated blinding of image reviewers. The registry does not give further details about how reviewer blinding is maintained or whether it applies to other assessments.

The primary endpoint is assessed immediately after repair. The registry also lists 22 outcome measures and two secondary-outcome descriptions concerning infants with an intact repair, defined as no cerebrospinal fluid leakage and no dehiscence at the repair site. Those two descriptions are effectively repeated in the record. No analysis results are listed. The detailed protocol, eligibility criteria, follow-up schedule, and full outcome-assessment procedures 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.

Before assignment: 50 Pregnant women were enrolled each with one fetus for a total of 100 participants enrolled.

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.

Population: Baseline Characteristics were only collected from the pregnant women participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Pregnant Women With Successful Fetoscopic Repair of the Defect Using NEOX Cord 1K®, measured over Immediately after repair procedure.

The primary endpoint is the number of pregnant women with successful fetoscopic repair of the defect using NEOX Cord 1K®. It is a participant count, and the assessment is scheduled immediately after the repair procedure. The description says a digital image of the fetal repair site is captured during and immediately after the procedure and sent to 3 independent blinded neurosurgeons for review of successful closure.

This endpoint focuses on whether the repair appears closed at the operative site. In general, an immediate technical endpoint can describe procedural completion without requiring later clinical follow-up. It does not, by itself, establish whether the repair remains intact or whether postnatal outcomes change. The registry’s proposed purpose is to create a watertight seal and decrease postnatal morbidities, but the primary endpoint itself is the immediate assessment of closure.

The endpoint description says that “More than best of three votes” will be considered as the result. That wording does not make the precise voting rule clear, so the threshold for classifying a repair as successful cannot be determined from the registry record. The number of successful repairs and its statistical uncertainty are not reported in the registry record. As a result, the endpoint is defined, but the posted information does not establish the observed success count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives the primary outcome as a participant count: the number of pregnant women with successful fetoscopic repair. A count records how many participants meet a defined criterion. Here, the criterion is an image-based judgment of successful closure immediately after repair. The outcome description does not provide the observed count, so no estimate of the proportion meeting the criterion can be interpreted from the record.

What does an immediate endpoint measure?

An immediate endpoint concerns the state of the repair at or near the procedure. In general, this can be useful for describing technical completion and making the assessment time explicit. It does not automatically represent outcomes at later follow-up. A repair judged closed immediately may need separate follow-up assessments to establish whether it remains intact, and an immediate technical assessment is not interchangeable with later morbidity or development outcomes. The registry identifies immediate assessment as the primary timeframe; additional timing details are not reported in the registry record.

The endpoint uses digital images reviewed by 3 independent blinded neurosurgeons. Independent review can help make an assessment less dependent on a single reviewer. Blinding, in general, can reduce the influence of knowledge about treatment or other participant information on a judgment. The record does not report how reviewer agreement is evaluated, how disagreements are resolved, or what exact voting threshold defines success. In particular, its wording, “More than best of three votes,” is unclear as a decision rule. The registry therefore identifies a review process but does not fully specify how the individual reviews become the final endpoint classification.

Why does the design matter?

The study is listed as single-group, and allocation is NA. In general, a single-group design can describe outcomes in the treated group but cannot by itself separate an intervention effect from other explanations for those outcomes. A control group gives a concurrent basis for comparison, while random allocation is used to reduce systematic differences between groups. Neither a concurrent comparison arm nor randomized allocation is described. Accordingly, a result from this study would be descriptive of the group studied rather than a randomized estimate of a difference between treatment strategies.

Masking is listed as NONE, while the primary endpoint description states that image reviewers are blinded. These entries do not necessarily refer to the same part of the process: the first is the trial’s masking entry, and the latter concerns endpoint review. The record does not explain the scope of the masking entry or provide further operational detail about the reviewers’ blinding.

What would uncertainty measures add?

In general, an estimate is more informative when accompanied by a measure of uncertainty. A confidence interval describes a range of values compatible with the data and analysis under the method’s assumptions. A hypothesis test addresses whether the data are inconsistent with a specified null hypothesis. Neither can be interpreted without the corresponding estimate, analysis method, and result. The registry record lists no analyses, and it does not report a primary endpoint estimate, confidence interval, or hypothesis-test result. There is therefore no inferential result to interpret for the primary endpoint.

The record’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are assumptions for an illustration, not a description of the trial’s single-group design. In general, sample-size calculations depend on the effect size being targeted and the statistical assumptions used. Such calculations do not show that an effect was observed, and they are not observed power. The trial’s own sample-size justification is not reported in the registry record.

Over-dispersion is a general concern for count outcomes when the variability exceeds what a simple model assumes. It can affect standard errors and the reliability of model-based uncertainty estimates. The primary endpoint is described as a count of participants meeting a binary success criterion, rather than a rate of repeated events. The registry does not report a model for this endpoint or an over-dispersion assessment. No such model should be inferred from the endpoint label alone.

How should adverse-event counts be read?

The adverse-event information gives counts of participants affected, alongside the numbers at risk, for pregnant women and children. These are descriptive summaries. A serious adverse event is distinct from the primary endpoint and may have a different definition, assessment window, and clinical meaning. In general, event counts do not establish causation. Attribution, timing, event handling, and the method used to collect events affect interpretation. Those details are not reported in the registry record. The serious-event terms and affected-participant counts should therefore be read as reported safety information, not as comparative estimates of intervention-related harm.

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("NEOX Cord 1K Applied Fetoscopically")
n      <- c(49)
events <- c(49)
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  NEOX Cord 1K Applied Fetoscopically  49  49  100.0  92.7  100.0  92.7  100.0  92.9  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 22 outcome measures, including a primary endpoint and secondary outcome descriptions about intact repair without cerebrospinal fluid leakage or dehiscence. Two secondary-outcome descriptions are repeated in substantially the same terms. The record does not report a multiplicity strategy for interpreting results across these outcomes. In general, testing or emphasizing many outcomes can increase the chance of findings that appear noteworthy by chance, so a prespecified hierarchy or adjustment approach can help clarify interpretation. No such approach is reported in the registry record.

The record lists no analyses. It does not report which outcome analyses were planned, whether any interim analyses were conducted, or whether any analysis plan specified how repeated assessments or multiple outcomes would be handled. Interim-analysis information and the statistical analysis plan are not reported in the registry record. The absence of these details means that analysis choices cannot be evaluated from the posted record.

Missing-data handling and analysis populations are also not reported in the registry record. The information does not specify how participants without an evaluable image would be classified, how incomplete outcome follow-up would be treated, or which participants would be included in each analysis. In general, missingness can affect estimates when the availability of an outcome is related to participant characteristics or outcome status. Without a stated approach and accounting of missing observations, the potential effect of missing data cannot be assessed.

The registry’s listed enrollment is 100, but the record does not give a flow of participants through screening, repair, endpoint review, and follow-up. It does not state how many images were available for review or how many participants contributed to each outcome. These omissions limit assessment of the analysis population and of whether the reported safety groups align with the primary endpoint population.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: etv or pv shunt placed (40.0%), preterm premature rupture of membranes (pprom) (38.0%), spontaneous preterm labor (30.0%), neonatal wound dehiscense at birth (12.0%), shunt revision (10.0%).

The serious adverse-event summaries list 50 pregnant women at risk, with 32 affected, and 50 children at risk, with 25 affected. The record separately lists 0 other adverse events affected among 50 pregnant women and 0 among 50 children. Deaths are listed as 0 in both groups. These figures are counts as recorded, not a comparison between an intervention group and a control group.

The registry also lists serious-event terms and percentages: ETV or PV shunt placed, 40.0%; preterm premature rupture of membranes (PPROM), 38.0%; spontaneous preterm labor, 30.0%; neonatal wound dehiscense at birth, 12.0%; shunt revision, 10.0%; and placental abruption at delivery, 8.0%. These are the terms reported in the record. The information does not provide event-level details, timing, attribution, or a breakdown of how the terms map to each participant.

In general, a count of participants affected does not necessarily equal the number of distinct events, because one participant may experience more than one event. The record does not clarify event overlap or establish that events were caused by the device or procedure. The figures should be read as descriptive safety reporting, not as a causal estimate or a comparison of risk with another treatment.

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

The registry record establishes that a trial was designed to evaluate fetoscopic use of NEOX Cord 1K® as a cover for fetal spina bifida defects. It defines an immediate image-based primary endpoint and describes review by 3 independent blinded neurosurgeons. It also lists serious adverse-event counts for pregnant women and children. These details describe the study question and selected reported measures.

The record does not report the result for the primary endpoint. It therefore does not show the number of pregnant women whose repair was judged successful, the uncertainty around such a count, or whether the stated endpoint criterion was met in any particular number of cases. The record also does not report analyses for the listed outcome measures. The design and the posted information do not support a claim of comparative benefit because there is no concurrent control group described.

The intended clinical rationale is to make a watertight seal over the spinal cord defect to decrease postnatal morbidities, with possible use as a skin cover for larger skin defects. That rationale should be distinguished from evidence about outcomes. An immediate image-based assessment of closure is not, on its own, evidence about durability, later morbidity, or comparative outcomes. The registry lists secondary outcomes related to intact repair, but their results are not reported in the registry record.

The adverse-event counts are important descriptive information, but they do not establish that the listed events were caused by the intervention. The registry does not provide a comparative safety analysis or the event-attribution details needed to make a causal interpretation. The listed terms also span different types of events, and the record does not provide enough detail to evaluate their timing or overlap.

Thus, the posted record describes a single-group procedural study, its intended endpoint, and selected safety counts. It does not provide the primary outcome result or a comparative analysis. Claims about the frequency of successful repair, precision of that frequency, or outcomes relative to another approach are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable because the central endpoint is a count from a single-group study rather than a randomized comparison. That design can provide a descriptive account of the experience in the treated group, but it does not create a direct estimate of how outcomes differ from another repair strategy. The distinction matters whenever a study’s rationale involves reducing later morbidity: an intended benefit is not the same as a measured comparative effect.

The endpoint also makes the assessment process consequential. The record specifies digital images and review by 3 independent blinded neurosurgeons, but does not clearly define the decision rule for classifying success. A reliable endpoint requires not only a measurement method, but also a reproducible rule for translating observations into a participant-level outcome. The phrase used for the voting threshold leaves that rule uncertain in the registry record.

Timing is another statistical consideration. The primary endpoint is assessed immediately after repair, while the stated rationale concerns postnatal morbidities. These are distinct types of outcomes. An immediate technical assessment may answer whether closure is judged successful at the procedure, but it cannot by itself answer questions about later integrity or morbidity. Separate follow-up outcomes and their results are needed for those questions.

Finally, the registry lists no analyses and does not report the primary endpoint result. Without an estimate and its uncertainty, readers cannot assess the observed frequency or precision of successful repair. The adverse-event counts add descriptive context but do not substitute for an endpoint analysis or a control-group comparison. These features make transparency about endpoint definitions, participant flow, missing data, and analysis plans especially important, yet those details are not reported in the registry record.

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 immediate limitation is that the primary endpoint result is not reported in the registry record. The endpoint is defined, but no count of successful repairs or measure of its uncertainty is available. The record lists enrollment as 100, but does not clarify whether that is the final number enrolled or a target, and it does not give a participant flow through repair and endpoint assessment.

The trial has a single-group design and no like-for-like control comparison. This limits interpretation to description of the group studied and prevents a direct estimate of how outcomes compare with open repair or another approach. The registry says that patients intending to undergo open in-utero repair may be offered screening for an alternative minimally invasive approach, but does not describe a control arm or report comparative results.

The primary endpoint’s voting rule is unclear. Although 3 independent blinded neurosurgeons review images, the phrase “More than best of three votes” does not define a precise classification threshold. Reviewer agreement and handling of disagreement are not described. The masking entry is NONE, while the endpoint description says reviewers are blinded; further details about the scope and conduct of blinding are not reported in the registry record.

The timing of the primary endpoint is immediate after repair, whereas the stated rationale concerns postnatal morbidities. The primary endpoint therefore does not by itself address longer-term integrity or morbidity. Although the registry lists secondary outcomes involving intact repair, their results are not reported in the registry record.

Other limitations include the absence of listed analyses, a statistical analysis plan, missing-data procedures, analysis-population definitions, and information about interim analyses. The registry also does not report detailed eligibility criteria, event attribution, or safety-event timing. These gaps constrain assessment of both effectiveness-related outcomes and safety reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fetoscopic NEOX Cord 1K® Spina Bifida Repair — NCT04243889.
• Registry record last updated 2026-08-25; status last verified 2026-07.
• Results first posted 2026-08-25.
• 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

NCT04243889 is a single-group interventional study of fetoscopic spina bifida repair using the cryopreserved human umbilical cord allograft NEOX Cord 1K®. The listed primary endpoint is the number of pregnant women with successful repair, assessed immediately after the procedure through review of images by 3 independent blinded neurosurgeons. The registry lists enrollment as 100, allocation as NA, and masking as NONE. The study is listed as active, not recruiting.

The record lists 22 outcome measures and no analyses. It reports serious adverse events affecting 32 of 50 pregnant women and 25 of 50 children, with 0 other adverse events affected and 0 deaths in each group. The primary endpoint result, analysis methods, missing-data approach, and comparative outcomes are not reported in the registry record. The design has no concurrent control group, so the posted information is descriptive rather than a randomized comparison.