Curosurf and Survanta Treatment(CAST)of RDS in Very Premature Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Curosurf and Survanta Treatment(CAST)of RDS in Very Premature Infants (NCT00767039), a randomized phase 4 study. The primary outcome is Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration..

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group, phase 4 study with no masking. It lists 52 enrolled participants and a terminated status. The study start is recorded as 2005-01 and primary completion as 2008-09. The reason for termination is not reported in the registry record. The record lists Alan Fujii as sponsor.

Participants were assigned to beractant (Survanta) or poractant alfa (Curosurf). The regimens differed in initial dose, spacing of subsequent doses, and the maximum number of doses: the beractant regimen used an initial dose of 100 mg/kg and up to 4 doses, while the poractant alfa regimen used an initial dose of 200 mg/kg and up to 3 doses. Both were described as intratracheal treatment for very premature infants with respiratory distress syndrome who required mechanical ventilation. The registry does not report additional details about how randomization was generated or concealed.

The primary endpoint was mean airway pressure at 48 hours after surfactant administration. The record says the primary analysis included enrolled subjects surviving >= 3 days and excluded two subjects in the beractant groups who died during that period. The displayed primary comparison has 25.0 participants in each arm. How those analysis counts relate to the total enrollment of 52, including the precise accounting of participants who did not contribute to the endpoint, is not reported in the registry record.

The registry lists 11 outcome measures and 11 analyses, including secondary outcomes concerning extubation, patent ductus arteriosus, cerebral artery blood flow, bronchopulmonary dysplasia, and death. It reports a result for the primary mean airway pressure endpoint and for a secondary patent ductus arteriosus endpoint. Numerical results for the other listed secondary outcomes are not reported in the registry record. The original sample-size target and the trial's own design assumptions 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: Enrolled subjects surviving \>/= 3 days were included in the analysis. Two subjects in the Survanta (beractant) groups died in this period and were eliminated from this portion of the analysis.

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 Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration., measured over 48 hours after surfactant administration.

The primary endpoint is mean airway pressure, measured in cm H20, 48 hours after surfactant administration. The registry describes it as pressure delivered by a mechanical ventilator or nasal CPAP. For mechanically ventilated infants, it notes use of a volume cycle ventilator strategy that allowed airway pressure to vary as lung and chest wall compliance changed; inspired oxygen concentration was controlled by the clinical team.

Mean airway pressure is a continuous measure of respiratory support at a defined time point. In general, a measure of support can help describe the respiratory assistance being delivered, but it is not identical to a direct measure of lung injury, survival, or overall clinical benefit. Its interpretation depends on the clinical context and on how support was managed. The registry's description of variable ventilator pressure and clinician-controlled oxygen underscores that the recorded value reflects both an infant's condition and the care being delivered.

The comparison is therefore about the average airway pressure in the two groups at 48 hours, among the population specified for analysis. It does not, by itself, describe the full course of respiratory support, later outcomes, or every complication of prematurity. The registry does not report a protocol-defined threshold for interpreting a difference in this measure, nor does it report a minimum clinically important difference. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Poractant Alfa Arm: mean 6.40 versus 8.60 on control; difference -2.20 (95% CI -3.95 to -0.45), standardized effect d = -0.70; z-test p = 0.014.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Poractant Alfa Arm: 32.0% (8/25) versus 76.0% (19/25) on control; risk difference -44.0 percentage points (95% CI -68.8 to -19.2), risk ratio 0.42 (0.23–0.78); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Poractant Alfa Arm than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes span several domains: successful extubation at 48 hours and 72 hours, hemodynamically significant PDA, changes in PDA blood flow after a second surfactant dose, change in anterior cerebral artery blood-flow velocity after a second dose, bronchopulmonary dysplasia defined by supplemental oxygen at 36 weeks post menstrual age, and bronchopulmonary dysplasia or death before NICU discharge. The registry reports a numerical comparison for hemodynamically significant PDA. Numerical results for the other listed secondary outcomes are not reported in the registry record.

The posted PDA comparison is directionally compatible with the primary comparison in the limited sense that both report a difference between treatment groups. It does not establish that all respiratory, circulatory, neurologic, or later outcomes followed the same pattern. With no numerical findings for the other secondary endpoints, an overall consistency across outcomes cannot be assessed from the registry record. Nor can the primary airway-pressure measure be treated as a proxy for every secondary outcome: the endpoints measure different events and processes.

Secondary findings generally carry less confirmatory weight when many outcomes are examined without a reported adjustment for multiple testing. If each outcome is tested separately, the chance of at least one apparently notable result can increase as the number of tests grows. This is a general statistical concern, not evidence that any particular finding is false. The registry lists 11 outcome measures and 11 analyses, but whether the analysis plan specified a hierarchy, adjustment, or other approach to multiplicity is not reported in the registry record. The PDA result is therefore best interpreted as a secondary comparison within a broader outcome set, rather than as independent confirmation of the primary result.

Because results are unavailable for several listed secondary outcomes, the posted evidence is incomplete for assessing the wider clinical picture. The absence of posted numbers should not be read as showing no difference or no events. It means the registry record does not permit those comparisons to be evaluated quantitatively.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
• Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
• Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)
• Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf)
• Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant
• Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age)
• Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) or Death Before Discharge From NICU.

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference describe?

A mean difference expresses the gap between two group averages on the original measurement scale. Here, the recalculated comparison is poractant alfa minus beractant, so a negative value corresponds to a lower average mean airway pressure in the poractant alfa group. The estimate is -2.2 cm H20. Keeping the units attached to the estimate makes its scale clear; it is not a standardized effect or a percentage change. The reported group means are 6.4 cm H20 for poractant alfa and 8.6 cm H20 for beractant.

The registry reports standard errors of 0.4 and 0.8 for the two group means. A standard error describes uncertainty in an estimated mean, rather than the spread of individual participants' measurements. The recalculation uses the posted summaries to estimate the difference and its uncertainty. It is described as unadjusted because it does not incorporate covariate adjustment or other features of a model that are not included in the posted summaries. The registry does not report a primary model specification beyond a two-sided t-test.

What does the t-test contribute?

A two-sided t-test evaluates evidence against equal group means while allowing a difference in either direction. In general, the p-value describes how compatible the observed data are with the test's null model; it is not the probability that the null hypothesis is true, nor does it measure the clinical importance of the estimate. The registry reports p < 0.05 for the primary comparison. The unadjusted recalculation reports p = 0.014. Since a discrepancy is flagged, the sponsor's own result takes precedence. The registry does not post enough detail to determine whether its analysis used exactly the same calculations or assumptions as the simple recalculation.

Why do the analyses have different levels of detail?

The primary registry analysis identifies a two-sided t-test but does not provide a test statistic, exact p-value, or confidence limits. The recalculated result supplies an estimate and interval based on the arm-level summaries. These are not interchangeable accounts of the analysis: the registry's result is the sponsor's stated test, while the recalculation is a simple, unadjusted reconstruction. A difference between them can arise when the underlying methods or data differ, but the registry does not report a reason for the flagged discrepancy. It would therefore be inappropriate to infer which unreported analytic choice caused it.

For the patent ductus arteriosus outcome, the registry reports a Mantel Haenszel risk ratio. This method combines comparisons across strata when stratified data are available. However, stratification details are not reported in the registry record. The recalculation instead describes the difference between the posted proportions in the two arms. A risk ratio and a risk difference answer related but distinct questions: one compares relative occurrence, while the other expresses the difference on the probability scale. The posted registry estimate is 2.38 for its stated risk-ratio analysis; the recalculated risk difference is expressed as poractant alfa minus beractant. They should not be treated as duplicate versions of one estimate.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when the variability in observed data is greater than a statistical model expects. If a model assumes less variability than the data contain, its uncertainty estimates can be too small and its statistical evidence can appear more precise than warranted. A suitable model may need to account for extra variability, clustering, or other features of the data. The registry does not report whether over-dispersion was assessed or relevant to these analyses. The primary continuous endpoint is described with a t-test; no extra variance adjustment is specified in the registry record.

What is known about analysis populations?

The primary endpoint's stated population is enrolled subjects surviving >= 3 days, with two beractant-group deaths in that period excluded. This rule means that the primary estimate applies to the specified analysis population rather than automatically to every enrolled infant. The registry does not report a broader intention-to-treat analysis for this endpoint, the handling of other missing measurements, or whether participants were analyzed according to randomized assignment in every outcome. These details are not reported in the registry record and should not be inferred from the arm counts alone.

General explanation: excluding participants after randomization can affect how well an estimate represents the original randomized groups, especially when exclusion is related to health status or outcome. In this record, early deaths are explicitly excluded from the primary pressure analysis, so the estimate should be read with that limitation in mind. The registry does not provide sufficient information to quantify the effect of this exclusion or to determine how alternative missing-data approaches would change the result.

What can p-values and confidence intervals say together?

A p-value and a confidence interval present related but different information. The p-value summarizes evidence against a specified null hypothesis under the test assumptions. The interval gives a range of estimates compatible with the data and method at its stated confidence level. Neither removes uncertainty, proves a causal mechanism, or establishes clinical importance. For the primary endpoint, the recalculated interval excludes zero, while the sponsor reports p < 0.05. The discrepancy flag means the sponsor result takes precedence for the trial's own analysis. For the secondary PDA endpoint, the registry and recalculation use different effect measures and confidence levels, so interpretation should preserve those distinctions.

The registry does not report the assumptions behind its primary test in detail, the handling of all potential departures from those assumptions, or whether any sensitivity analyses were performed. Those aspects of the statistical plan are not reported in the registry record. Accordingly, the displayed estimates support a focused reading of the posted comparisons, not a reconstruction of the full analysis plan.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -2.2 cm H20, with a 95% confidence interval from -3.953 to -0.447. In general, a confidence interval describes the uncertainty around an estimate under the statistical method used. It is not a range guaranteed to contain the true effect, and it does not express the probability that an individual participant's value will fall in the interval. The interval is for the group mean difference, not for individual airway pressure readings.

The primary interval lies on the negative side of zero, consistent with the direction of the recalculated estimate: a lower mean airway pressure in the poractant alfa arm in this comparison. Its width also indicates that the estimate is not exact. The sponsor's own analysis reports a two-sided test with p < 0.05 but does not provide its confidence interval. Because a discrepancy is flagged, the sponsor's analysis takes precedence; the recalculated interval is useful as an unadjusted description of precision, not as a replacement for the sponsor's result.

For the secondary PDA comparison, the recalculated risk difference is -0.44 with a 90% confidence interval from -0.688 to -0.192. The sponsor reports a risk ratio of 2.38 with a 95% confidence interval from 1.29 to 4.38. The interval levels and effect measures differ, so their apparent widths cannot be directly compared. In general, wider intervals indicate less precision, and interval width depends on the measure, method, and amount of information available.

The primary arm summaries include 25.0 participants each, while the primary analysis population also excludes two early deaths in the beractant groups. The registry does not report confidence intervals for the arm means or a sponsor-reported interval for their difference. Precision should therefore be judged from the estimates and intervals that are actually posted, while keeping the analysis-population restriction and the discrepancy in view.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial's original design calculation. For the continuous primary endpoint and the PDA comparison, the figures are participants per arm. In a time-to-event planning display, the convention would instead be total events; no time-to-event planning results are reported for the comparisons.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The 80% power column indicates the number of participants per arm under those assumptions for an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are hypothetical design calculations, not guarantees about the result of a future study.

The rows consider 100%, 75%, and 50% of the observed effect. For the primary mean difference, the corresponding figures are 33, 58, and 130 participants per arm for 80% power, and 44, 78, and 174 participants per arm for 90% power. For the PDA endpoint, they are 19, 34, and 73 participants per arm for 80% power, and 25, 45, and 97 participants per arm for 90% power. These are illustrations under the stated assumptions, not the trial's enrollment target.

Smaller effects require more participants to detect with the same planned power, because a smaller signal is harder to distinguish from random variation. In general, a curve based on these planning values depicts that relationship across effect sizes. The trial's original design assumptions and sample-size justification are not reported in the registry record. This is not observed power: it does not measure the probability that the completed trial detected an effect, and it should not be used to reinterpret the observed p-value.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.200; pooled standard deviation σ = 3.162.
2. n = 2 × (1.96 + 0.842)² × 3.162² / -2.200² = 32.4, rounded up to 33 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.2                      # observed difference in means
sigma <- 3.16227766016838                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(767039)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 33 (80% power), 44 (90% power)
 75% of observed effect: n per arm = 58 (80% power), 78 (90% power)
 50% of observed effect: n per arm = 130 (80% power), 174 (90% power)
power.t.test: 33.4 
Simulated power at n = 33 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry's primary analysis is a two-sided t-test and reports p < 0.05. It does not post the sponsor's estimated mean difference, confidence interval, or exact p-value. A separate unadjusted recalculation from the posted arm summaries gives a mean difference of -2.2 cm H20, a 95% confidence interval from -3.953 to -0.447, and p = 0.014. The direction of that recalculation corresponds to a lower mean airway pressure in the poractant alfa group.

The record flags a discrepancy. Under that circumstance, the sponsor's own analysis takes precedence over a simple recalculation. The recalculated estimate and interval can still help describe the magnitude and precision implied by the posted summary statistics, but they should not be presented as the sponsor's original result. The registry does not explain the discrepancy or provide sufficient details to identify its cause. It is therefore not appropriate to attribute the difference to a particular test assumption, data adjustment, or analysis population.

For the PDA outcome, the registry's own analysis is a Mantel Haenszel risk ratio of 2.38, with a 95% confidence interval from 1.29 to 4.38 and p < 0.01. The recalculation gives a risk difference rather than a risk ratio, with a 90% confidence interval and a different p-value. Since these are distinct effect measures, the recalculated risk difference is not a substitute for the sponsor's stated risk-ratio analysis. For both outcomes, sponsor-reported analyses should be distinguished clearly from unadjusted recalculations based on posted summaries.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and 11 analyses, including one primary endpoint and multiple secondary endpoints. The record does not report whether the statistical plan used a testing hierarchy, adjusted significance thresholds, or another method to address multiplicity. That information is not reported in the registry record. In general, when many outcomes are tested, some results may appear statistically notable by chance even if there is no underlying difference for those outcomes. This is why unadjusted secondary results are usually interpreted more cautiously than a single prespecified primary comparison.

The registry reports two-sided testing for the primary endpoint, but does not describe a broader multiplicity strategy. The PDA analysis is reported as a Mantel Haenszel risk ratio with p < 0.01; the registry does not state whether this test was adjusted for the number of secondary outcomes. The unadjusted recalculation is explicitly an unadjusted comparison. Without a reported plan, it is not possible to determine whether the posted p-values were intended as confirmatory evidence or as descriptive analyses.

The analysis population for the primary endpoint is described as enrolled subjects surviving >= 3 days. Two subjects in the beractant groups died in this period and were excluded from that analysis. The display gives 25.0 participants in each arm for the primary comparison, while total enrollment is 52. The registry does not report a complete accounting of all randomized participants, endpoint availability, or the reasons for any other exclusions or missing measurements.

The registry does not report how missing data were handled for the primary endpoint or other outcomes, whether any imputation was used, or whether sensitivity analyses assessed the consequences of missingness. It also does not provide enough detail to establish whether every analysis followed randomized assignment. These points should not be filled in by assumption. The stated exclusion of early deaths is particularly important because it means the primary endpoint is conditional on surviving the specified period, rather than an endpoint that directly incorporates those deaths.

The reason for the terminated status, the original sample-size rationale, interim analyses, and the complete statistical analysis plan are not reported in the registry record. Without those details, readers cannot determine whether trial conduct or analysis changed over time, or whether the posted comparisons reflect all planned analyses. This limits the degree to which the statistical findings can be assessed beyond the information explicitly recorded.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: rop stage ii-iv (43.5%), death (18.5%), necrotizing enterocolitis (16.0%), significant pulmonary hemorrhage (11.1%), severe intraventricular hemorrahge (grade 3-4) (4.0%).

The registry reports serious adverse events for 19 of 27 participants at risk in the beractant arm and 9 of 25 participants at risk in the poractant alfa arm. It reports other adverse events for 17 of 27 at risk in the beractant arm and 8 of 25 at risk in the poractant alfa arm. These are the posted counts and denominators; they should not be converted into a comparative safety conclusion without additional information about definitions, event timing, follow-up, and the way participants could contribute to more than one event category.

The registry lists serious-event terms and percentages: ROP Stage II-IV, 43.5%; Death, 18.5%; Necrotizing Enterocolitis, 16.0%; Significant Pulmonary Hemorrhage, 11.1%; and Severe Intraventricular Hemorrahge (Grade 3-4), 4.0%. The denominator and precise calculation underlying these percentages are not reported in the registry record. The group-level death fields are null, so a death count by arm is not available from those fields; the listed Death percentage should not be used to infer one.

These figures describe what the registry posts, not whether one treatment is safer. The record does not provide enough detail to establish event severity rules, adjudication, exposure time, or comparative uncertainty for the adverse-event counts. Safety interpretation should remain descriptive and account for the trial's limited enrollment and terminated status.

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

The posted primary result indicates that the two groups had different average mean airway pressures at 48 hours in the analysis population described by the registry. The recalculated difference is -2.2 cm H20 for poractant alfa relative to beractant, with a 95% confidence interval from -3.953 to -0.447. The sponsor reports a two-sided p-value of p < 0.05. Because the record flags a discrepancy, the sponsor's own analysis takes precedence; the recalculation is an unadjusted description based on the posted summaries.

This statistical result does not, on its own, establish that one treatment improves survival, prevents complications, or produces a clinically important benefit. Mean airway pressure is a respiratory-support measure at a specific time, not a complete summary of an infant's clinical course. It can be influenced by both patient condition and clinical management. The endpoint population also excludes two beractant-group deaths during the initial period described by the registry, so the pressure comparison does not incorporate those deaths as part of the endpoint.

The secondary PDA comparison adds a separate posted result, but the record does not provide numerical results for most listed secondary outcomes. It therefore cannot establish whether differences in mean airway pressure aligned with extubation, blood-flow measures, bronchopulmonary dysplasia, or death. The reported secondary result also sits among multiple outcomes, and a multiplicity adjustment is not reported.

Confidence intervals and p-values describe statistical uncertainty under particular methods; they do not answer whether an observed difference matters to patients or clinicians. The registry does not report a minimum clinically important difference for mean airway pressure, nor does it provide a complete account of missing data, analysis populations, or the reason for termination. These limitations constrain interpretation. The findings should be understood as comparisons in the posted record, not as medical advice or a recommendation about treatment.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint and its analysis population need to be read together. Mean airway pressure at 48 hours is a continuous measure of respiratory support. The reported primary analysis is restricted to enrolled subjects surviving >= 3 days, with two early deaths in the beractant groups excluded. A statistical comparison of pressure among that population does not answer the same question as a comparison that includes every randomized participant or an outcome that combines death and respiratory support.

It also demonstrates the difference between a sponsor-reported analysis and a summary-statistic recalculation. The registry reports a two-sided t-test with p < 0.05, while the unadjusted recalculation adds a mean difference and confidence interval. The record flags a discrepancy, so the sponsor's analysis takes precedence. Reporting both clearly preserves the distinction between the trial's own result and a simple reconstruction from posted group summaries.

The secondary PDA result raises another statistical distinction: a risk ratio and a risk difference communicate different scales of comparison. The registry's Mantel Haenszel risk ratio is not interchangeable with the recalculated difference in group proportions. In addition, several secondary outcomes are listed without numerical results, and the registry does not report a multiplicity plan. These details matter when deciding how much weight to place on a single secondary finding.

Finally, the sample-size illustrations are based on observed effects and stated planning assumptions, not the original trial design. They demonstrate how planning needs change when the target effect becomes smaller, but they cannot explain why the trial enrolled 52 participants or establish its intended power. The original justification is not reported in the registry record. Together, these features make the trial a useful example of how population definitions, effect scales, uncertainty, and incomplete reporting shape statistical interpretation.

19. 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 registry records a terminated status but does not report the reason. It lists 52 enrolled participants, while the primary comparison has 25.0 participants in each arm and the primary analysis excludes two beractant-group deaths during the first 3 days. A full accounting of enrollment, randomization, exclusions, and endpoint availability is not reported in the registry record. The effect of the population restriction on the estimate cannot be determined from the posted information.

The record describes randomization and a parallel-group design without masking, but details of sequence generation, allocation concealment, or procedures to limit measurement bias are not reported. The primary outcome involves a clinical support measure that can vary with patient condition and clinical management. Although the registry describes how ventilator pressure and inspired oxygen were managed, it does not report whether outcome assessors were blinded or whether standardization beyond that description was used.

The sponsor's primary analysis gives only a two-sided t-test and p < 0.05. The discrepancy flag and absence of a sponsor-reported estimate, interval, or exact p-value limit independent assessment of that analysis. The recalculated primary estimate is unadjusted. The registry does not report a detailed model, covariate adjustments, sensitivity analyses, or assumptions for handling missing measurements.

Most secondary outcomes have no posted numerical results, and adjustment for multiple testing is not reported. The original sample-size assumptions, sample-size justification, interim analyses, and complete statistical plan are also not reported in the registry record. Serious adverse-event percentages are listed without a stated denominator, while group-level death fields are null. These reporting gaps limit assessment of both the full outcome pattern and safety comparisons.

The findings are therefore most informative as a description of the specific posted analyses. They should not be generalized beyond the population, outcomes, and follow-up information recorded in the registry. The reason for termination and the extent to which the posted results represent all planned analyses remain unknown.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Curosurf and Survanta Treatment(CAST)of RDS in Very Premature Infants — NCT00767039.
• Registry record last updated 2011-10-03; status last verified 2008-10.
• Results first posted 2011-09-20.
• 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.

23. Record Summary

NCT00767039 is a randomized, unmasked, parallel-group phase 4 study of beractant (Survanta) and poractant alfa (Curosurf) in very premature infants with respiratory distress syndrome. The registry lists 52 enrolled participants and a terminated status; the reason for termination is not reported in the registry record.

The primary endpoint is mean airway pressure 48 hours after surfactant administration. The registry reports a two-sided t-test with p < 0.05. The unadjusted recalculation gives a mean difference of -2.2 cm H20, with a 95% confidence interval from -3.953 to -0.447; because a discrepancy is flagged, the sponsor's own analysis takes precedence.

A secondary comparison reports hemodynamically significant PDA, while numerical results for most other listed secondary outcomes are not reported in the registry record. The primary analysis excludes two beractant-group deaths during the initial period described. Original design assumptions, multiplicity methods, and a complete account of missing data are not reported.