Comparison of Curosurf and Infasurf in the Treatment of Preterm Infants With Respiratory Distress Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Curosurf and Infasurf in the Treatment of Preterm Infants With Respiratory Distress Syndrome (NCT02834624), a randomized na study. The primary outcome is Change From Baseline in Blood C-reactive (CRP) Protein.

2. Clinical Question

The comparison concerns two surfactant treatments for respiratory distress syndrome in preterm infants. The registry record describes poractant as containing added phospholipids and says the investigators planned to compare samples from the windpipe and blood. That description gives the motivation for the comparison; it does not establish that any biological difference or safety difference occurred.

The posted primary outcome is specifically a change in C-reactive protein (CRP), rather than a clinical event or a measure of breathing support. Pulmonary hemorrhage and change in tracheal macrophages are also identified as secondary outcomes. The record does not report a separate quantitative pulmonary hemorrhage outcome result. The CRP comparison therefore addresses one measured aspect of the trial’s stated question, not every aspect of safety or treatment experience.

3. Trial Design

The registry record identifies NCT02834624 as a completed, randomized, triple-masked, parallel-group trial sponsored by the University of Missouri-Columbia. Enrollment was 30. The record lists the phase as NA. It lists respiratory distress syndrome as the condition under study and describes the participants as preterm infants.

Participants were assigned to poractant or calfactant. The posted primary outcome reports 15 participants in each group. The arm descriptions identify the products as Curosurf and Infasurf, respectively, and specify doses of 3ml/kg, repeated as needed according to the attending neonatologist. The record does not give further detail about the randomization sequence, allocation concealment, or the procedures used to maintain masking.

The study dates listed in the registry record are a start in 2013-07 and primary completion in 2015-02. The trial status is completed. These dates describe the registered study timeline; they do not give the timing of each participant’s treatment or follow-up.

The primary outcome was change from baseline in blood CRP at 48 hours. The record also lists presence of pulmonary hemorrhage and change in the number of tracheal macrophages as secondary outcomes. The macrophage outcome is reported as a mean and standard deviation, with measurements at baseline and 48 hours. A quantitative pulmonary hemorrhage outcome result is not reported in the registry record.

The registry record does not report the trial’s original sample-size justification, its planned statistical analysis protocol, or the specific analysis population. Those omissions limit what can be said about whether the completed enrollment matched an original target or how participants with missing outcome measurements were handled.

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.

Population: Preterm infants less than 35 weeks gestation who required intubation for RDS and surfactant administration

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Blood C-reactive (CRP) Protein, measured over baseline, 48 hours.

The primary endpoint is the change in blood C-reactive protein (CRP) from baseline to 48 hours after surfactant administration, measured in mg/dL. The registry record describes it as the difference between the CRP measurement at baseline and the measurement at 48 hours. It reports the mean change and standard deviation for each treatment group.

CRP is a blood protein used as a marker associated with inflammation. As a general clinical measurement, changes in a marker can help describe a biological response over a specified period. That makes a measured change different from a single value: the comparison concerns how the measurement changes between the stated time points. The record’s description of the study emphasizes concern about inflammation and irritation, but it does not report a detailed rationale for selecting CRP as the primary endpoint.

This endpoint is a laboratory measure, not a direct measure of breathing function, survival, or a clinical diagnosis. A difference in average CRP change therefore describes the laboratory outcome reported for these groups; by itself it does not establish a difference in other outcomes or overall safety. The 48-hour measurement also represents the stated endpoint time, not a longer-term assessment.

7. Results Posted in the Registry

• Calfactant: mean 0.19 versus 1.30 on control; difference -1.11 (95% CI -1.96 to -0.26), standardized effect d = -0.93; z-test p = 0.011.

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.

Change in Number of Tracheal Macrophages

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Calfactant: mean 2.00 versus 2.30 on control; difference -0.30 (95% CI -1.39 to 0.79), standardized effect d = -0.20; z-test p = 0.591.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Calfactant and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add context to the primary laboratory comparison, but they do not provide a consistent set of results across all aspects of the study’s stated safety question. The macrophage outcome is reported quantitatively, while pulmonary hemorrhage is identified as a secondary outcome without a dedicated numerical result in the registry record. The secondary evidence therefore has gaps as well as statistical uncertainty.

The macrophage comparison does not show the same degree of separation as the recalculated primary CRP comparison: its confidence interval includes zero, and its unadjusted p-value is 0.591. The sponsor’s reported one-sided test gives p=0.63. These summaries do not establish a difference, but they also do not demonstrate that the groups are equivalent. A result that is not statistically distinguishable from zero can reflect a small effect, considerable uncertainty, or both.

Secondary outcomes are generally interpreted with less weight than a prespecified primary outcome, particularly when several outcomes are examined. If each outcome is tested separately without adjustment, the chance of at least one apparently notable result can increase across a family of comparisons. The registry record does not report whether a multiplicity adjustment was planned or used. The secondary results should therefore be treated as exploratory context rather than as independent confirmation of the primary result.

The difference in the amount of available information also matters. One named secondary outcome has posted group summaries and a comparison; the other does not have a quantitative result reported in the registry record. Taken together, the secondary outcomes do not resolve the broader safety question or establish that the primary CRP pattern extends to other measures.

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

• Presence of Pulmonary Hemorrhage
• Change in Number of Tracheal Macrophages

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical change in CRP, summarized by a group mean and standard deviation. A mean difference compares the average outcome between two groups. In this comparison, the stated direction is calfactant relative to poractant. A negative mean difference indicates a lower average change in the calfactant group based on the posted group summaries; it does not describe every participant’s result.

The recalculated comparison uses the posted means, standard deviations, and group sizes to estimate an unadjusted difference. “Unadjusted” means that the calculation compares the group summaries without accounting for additional covariates or other adjustments. The posted primary summaries are a mean change of 1.3 mg/dL for poractant and 0.193 mg/dL for calfactant, with 15 participants in each group. The resulting recalculated mean difference is -1.107 mg/dL. This is a reconstruction from summary statistics, not a substitute for the trial’s own participant-level analysis.

A standard deviation describes how spread out observations are around a group mean. It is not the same as a standard error, which describes uncertainty in an estimated mean. For the primary outcome, the posted standard deviations are 1.644 in the poractant group and 0.337 in the calfactant group. Differences in spread matter because they affect the uncertainty of a mean comparison. With a small sample, a few observations can have substantial influence on a mean and its estimated uncertainty.

The registry record reports the sponsor’s primary analysis as a one-sided t-test and gives its p-value as <.05, without reporting the test statistic or an exact p-value. A t-test assesses whether a difference in group means is inconsistent with a specified null hypothesis under the test’s assumptions. A one-sided test evaluates evidence in a single direction, unlike a two-sided test, which allows evidence in either direction. The registry does not report the sponsor’s full statistical plan or enough detail to reconstruct that analysis exactly.

The independent recalculation reports an unadjusted p-value of 0.011 and a confidence interval for the mean difference. These values are not the sponsor’s reported analysis. The record flags a discrepancy between the posted analysis and the recalculated result, so the sponsor’s own analysis takes precedence. The recalculation can still help readers understand the group summaries, but it should not be presented as the definitive trial analysis.

A p-value describes how unusual results at least as inconsistent with a null hypothesis would be under the test’s assumptions if that null hypothesis were true. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The sponsor’s threshold-style result, <.05, is less specific than an exact p-value. Neither the sponsor’s p-value nor the recalculated p-value, on its own, describes the uncertainty and magnitude as fully as an estimate with a confidence interval.

A confidence interval gives a range of estimates compatible with the data under a specified statistical procedure. For the primary recalculation, the interval lies entirely below zero, which is consistent with a negative mean difference for calfactant relative to poractant. The interval does not account for every possible bias, design limitation, missing-data issue, or choice of analysis. It also does not imply that individual participant outcomes lie within the interval.

The macrophage outcome is also continuous, with group means, standard deviations, and a recalculated mean difference. Its confidence interval includes zero. That pattern indicates uncertainty about both the direction and size of the group difference under the calculation; it does not prove that the groups are identical. The sponsor’s reported one-sided t-test p-value for this secondary outcome is 0.63, while the unadjusted recalculated p-value is 0.591. Since these are secondary results and several outcomes are named, isolated p-values should be interpreted cautiously.

Over-dispersion is a general concern when variability is greater than a model assumes. It can make standard errors and confidence intervals too small if the analysis fails to account for the extra variation. The posted primary group standard deviations are markedly different, and the small group sizes make variance assumptions consequential. The registry record does not report a variance diagnostic, robust analysis, or a detailed model specification, so it is not possible to determine from the record whether alternative variance methods were assessed.

Several parts of statistical interpretation depend on choices that are not reported: the original analysis population, how missing values were handled, whether the analysis followed randomized assignment, and whether outcome comparisons were adjusted for multiplicity. These are not details that can be recovered from the group means and standard deviations. The record also does not report the original sample-size justification, interim analyses, or the full statistical analysis plan. Consequently, the recalculated summaries should be treated as descriptive support for reading the posted results, not as evidence that the original design or analysis followed a particular unreported procedure.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an estimated group difference. The recalculated primary mean difference is -1.107 mg/dL, with a confidence interval whose lower endpoint is -1.956 and whose upper endpoint is below zero. Because the interval does not cross zero, it is consistent with a negative average difference under the calculation. The interval is still broad enough to leave uncertainty about the size of that difference.

A confidence interval is not a guarantee that the true effect lies inside its endpoints, and it is not a range containing most individual participants’ changes. It is a range generated by a statistical method that, under its assumptions, reflects uncertainty in the estimated group difference. It does not incorporate unreported design or analysis choices, possible missing data, or other sources of bias.

The primary comparison includes 15 participants in each group. That small number limits precision, even though the recalculated interval lies on one side of zero. The group standard deviations are 1.644 and 0.337, showing different levels of observed variability. A confidence interval should therefore be read alongside the group sizes and variability, not as a standalone verdict.

For the secondary macrophage comparison, the recalculated interval extends from -1.395 to an upper endpoint above zero. Its inclusion of zero indicates substantial uncertainty about the direction and magnitude of the difference. This does not prove there is no difference; it means the posted summaries do not estimate that difference precisely enough to exclude zero under this calculation.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculation. They give participants per arm for a continuous outcome, not total events. The stated 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 original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the number of participants per arm in a hypothetical study that would have an 80% chance of detecting the specified effect under those planning assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. These are design calculations for a possible study, not estimates of the probability that the completed trial detected an effect.

The rows use different planning effect sizes: 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The smaller the effect a future study is intended to detect, the more participants it generally requires, all else equal. For the primary outcome, the listed planning figures rise as the assumed fraction of the observed effect becomes smaller. They are especially sensitive to the observed effect because the trial itself enrolled only 15 participants per arm.

These figures are not observed power. Observed power is not a useful substitute for interpreting the estimate and its uncertainty after results are known; the planning figures instead illustrate how different target effects translate into possible enrollment needs under stated assumptions. They do not correct for missing data, multiplicity, or limitations not included in the planning assumptions.

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 = -1.107; pooled standard deviation σ = 1.187.
2. n = 2 × (1.96 + 0.842)² × 1.187² / -1.107² = 18.0, rounded up to 19 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 <- -1.107                      # observed difference in means
sigma <- 1.18665601586981                     # 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(2834624)
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 = 19 (80% power), 25 (90% power)
 75% of observed effect: n per arm = 33 (80% power), 43 (90% power)
 50% of observed effect: n per arm = 73 (80% power), 97 (90% power)
power.t.test: 19 
Simulated power at n = 19 per arm: 0.800 (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 record reports the sponsor’s primary analysis as a one-sided t-test with p <.05. It does not report an exact p-value, a test statistic, or a sponsor confidence interval for the primary comparison. For the macrophage outcome, the sponsor’s reported one-sided t-test p-value is 0.63.

The recalculated summaries use the posted group means, standard deviations, and sample sizes to produce unadjusted mean differences, confidence intervals, and p-values. They are not a reproduction of the sponsor’s analysis from participant-level data. The record flags a discrepancy, so the sponsor’s own analysis takes precedence. The recalculation is best understood as an additional way to read the posted summary statistics, not as a correction or replacement for the sponsor’s result.

The primary recalculated p-value is 0.011, while the sponsor reports only that its one-sided result is below .05. Those statements are not identical summaries: the registry’s result is threshold-based and comes from a one-sided test, whereas the recalculation gives an unadjusted p-value from posted summaries. Without the full analysis details, the record does not support attributing the difference to a particular methodological choice. Readers should retain the sponsor analysis as the reported trial analysis and use the recalculation as a separate summary-statistic-based estimate.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and two secondary outcomes, but it does not report whether the statistical plan adjusted for testing multiple outcomes. Multiplicity matters because examining several outcomes can increase the chance of at least one result appearing statistically notable by chance. Without a reported adjustment plan, the p-values for individual outcomes should not be treated as if they necessarily represent a single prespecified test.

The record also does not report the analysis population used for the posted results. It is therefore unclear whether the summaries include all randomized participants, only participants with measurements at both stated time points, or another defined group. The posted primary outcome lists 15 participants in each arm, but that alone does not establish how missing observations or withdrawals were handled.

Missing-data methods and the number of participants with outcome measurements at baseline and 48 hours are not reported in the registry record. If observations were missing, the method used to handle them could affect estimated group means and uncertainty. The record does not say whether any imputation, sensitivity analysis, or other missing-data assessment was performed.

The registry does not report a full statistical analysis plan, the original sample-size justification, or interim analyses. It also does not provide enough detail about the randomization procedure, allocation concealment, or analysis model to assess those features from the posted summaries. These omissions do not show that a particular method was or was not used; they mean the relevant information is not reported in the registry record.

16. 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.

For both treatment groups, the adverse-event summaries list 15 participants at risk for serious adverse events and 15 at risk for other adverse events. The record lists zero serious adverse events, zero other adverse events, and zero deaths in each group. No serious adverse-event terms are listed.

These figures describe the events recorded for the listed groups; they do not establish that no adverse effects occurred outside the registry’s reported categories or observation period. The record does not report the duration or completeness of safety follow-up, definitions used for adverse-event categories, or whether all randomized participants contributed to these summaries. With 15 participants per group, an absence of recorded events is also limited evidence about uncommon events.

The safety counts should be read alongside the study’s stated purpose and its laboratory outcomes, not as a complete comparison of all possible harms. The registry record’s zero counts do not, by themselves, establish that the treatments have equal safety profiles.

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

The posted results show a lower average change in CRP for the calfactant group than for the poractant group at the stated 48-hour endpoint. The recalculated mean difference is -1.107 mg/dL, and its confidence interval lies below zero. The sponsor’s own analysis reports a one-sided t-test with p <.05; because the record flags a discrepancy, that sponsor analysis takes precedence over the recalculation.

This result concerns the mean change in one blood measurement among the participants represented in the posted summaries. It does not establish a difference in breathing outcomes, long-term health, or every dimension of safety. The macrophage outcome is less conclusive, and a quantitative pulmonary hemorrhage result is not reported in the registry record. The adverse-event summaries list no events in either group, but the small groups and unreported follow-up details limit what can be inferred from those counts.

The trial enrolled 30 participants, with 15 per arm for the primary outcome. Such a small study can provide a preliminary estimate but leaves substantial uncertainty about how well the result would generalize to other participants or settings. The record also lacks details on missing data, analysis populations, multiplicity, and the original sample-size rationale. These reporting gaps make it difficult to assess the robustness of the result beyond the posted summaries.

The result should therefore be read narrowly: it is a comparison of average CRP change in this randomized trial, not a determination of overall treatment benefit or harm. A statistically notable difference in a laboratory endpoint does not by itself show that a treatment works or does not work, or that one treatment is safer overall.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation needs to distinguish an outcome estimate from the broader clinical question. The stated motivation concerns safety, while the primary endpoint is a short-term change in a blood biomarker. A precise interpretation keeps the claim tied to what was measured rather than extending it to unmeasured clinical outcomes.

It also shows the value of separating sponsor analyses from recalculations based on group summaries. The registry reports a one-sided t-test with a threshold p-value, while the recalculation supplies an unadjusted mean difference and confidence interval. These answer related but not identical statistical questions. The record flags a discrepancy, so the sponsor’s analysis takes precedence, while the recalculated estimate can still clarify the direction and scale of the posted group difference.

The small group sizes make precision an important part of the story. A confidence interval can indicate the range of differences compatible with the data, while the sample-size illustrations can show how a future study’s required enrollment depends on its target effect. Neither should be confused with proof that a finding will replicate or with observed power.

Finally, reporting gaps are statistically consequential. Without information about missing data, analysis populations, multiplicity, and the original design assumptions, readers cannot fully assess how the reported comparisons were planned or how sensitive they might be to analytic choices. This trial is a useful example of reading numerical results alongside the limits of what the registry record reports.

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 trial enrolled 30 participants, with 15 in each group for the primary outcome. The small sample constrains precision and makes the group estimates vulnerable to influence from individual observations. It also limits the information available about uncommon safety events; zero recorded events in these groups cannot rule out such events.

The primary endpoint is a laboratory measure of CRP change over the stated baseline-to-48-hour interval. It does not capture every clinical aspect of respiratory distress syndrome or safety. The record identifies pulmonary hemorrhage as a secondary outcome but does not report a dedicated quantitative result for it. The macrophage result is also statistically uncertain, so the secondary outcomes do not provide a complete or decisive assessment of the broader safety question.

The registry record does not report the original sample-size justification, a full statistical analysis plan, interim analyses, the analysis population, or the handling of missing data. It also does not report whether multiplicity was addressed. These missing details limit evaluation of whether the analyses followed a prespecified plan and how robust the estimates are to alternative analysis choices.

The sponsor’s analysis and the summary-statistic recalculation are not identical forms of evidence. The record flags a discrepancy, and the sponsor’s own analysis takes precedence. The recalculation does not use participant-level data and cannot resolve the reason for the discrepancy. Further details about randomization procedures, allocation concealment, and the duration of safety follow-up are also not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Comparison of Curosurf and Infasurf in the Treatment of Preterm Infants With Respiratory Distress Syndrome — NCT02834624.
• Registry record last updated 2017-06-06; status last verified 2017-05.
• Results first posted 2017-06-06.
• 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

NCT02834624 is a completed, randomized, triple-masked, parallel-group trial sponsored by the University of Missouri-Columbia. It enrolled 30 preterm infants with respiratory distress syndrome and compared poractant alfa with calfactant. The registry lists the study start as 2013-07 and primary completion as 2015-02.

The primary outcome was mean change in blood CRP from baseline to 48 hours. The posted group sizes were 15 per arm. The sponsor reported a one-sided t-test with p <.05; a recalculation from posted summary statistics estimated a mean difference of -1.107 mg/dL and an unadjusted p-value of 0.011. Because the registry flags a discrepancy, the sponsor’s analysis takes precedence.

Secondary outcomes included pulmonary hemorrhage and change in tracheal macrophages. A quantitative pulmonary hemorrhage result is not reported in the registry record. The posted adverse-event summaries list zero serious adverse events, zero other adverse events, and zero deaths in both groups. The original design assumptions, missing-data handling, analysis populations, and multiplicity procedures are not reported.