CALIPSO: Calfactant for Acute Lung Injury in Pediatric Stem Cell Transplant and Oncology Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CALIPSO: Calfactant for Acute Lung Injury in Pediatric Stem Cell Transplant and Oncology Patients (NCT00999713), a randomized phase 2, phase 3 study. The primary outcome is All-cause Mortality at the Time of Pediatric Intensive Care Unit (PICU) Discharge.

2. Clinical Question

The registry also lists secondary outcomes concerning ventilator-free days, total duration of stay and change in oxygenation after the first and second interventions. These outcomes provide context for the study’s broader aims, but their numerical results are not reported in the registry record. The primary comparison is therefore the focus of the statistical interpretation. The posted counts describe the observed participants in each randomized group; they do not, on their own, establish why outcomes differed or whether a similar pattern would occur in other settings.

3. Trial Design

CALIPSO was a randomized, parallel-group trial with quadruple masking. The registry lists both phase 2 and phase 3. Milton S. Hershey Medical Center was the sponsor. The trial started in 2010-06, reached primary completion in 2015-09 and is listed as completed. Enrollment was 43 participants.

Participants were assigned to endotracheal calfactant or endotracheal air placebo. The posted primary results include 26 participants in the calfactant group and 17 in the placebo group. These are the group sizes shown for the primary outcome. The registry does not report additional details about the randomization procedure, the identities of the people or roles covered by quadruple masking, or the reasons for the group-size imbalance.

The primary endpoint was all-cause mortality by PICU discharge, with the outcome period extending from PICU admission to discharge and capped at up to 120 days. The registry lists four secondary outcomes: ventilator-free days, total duration of stay, and changes in oxygenation after the first and second interventions. Although these outcomes are named, numerical findings for them are not reported in the registry record.

The registry record does not report the trial’s original sample-size justification, planned analysis methods, handling of missing data, or any interim-analysis plan. Those details should not be inferred from the posted sample-size illustration or the reported estimates. The study’s registered phase, allocation, masking and endpoint describe its general structure, but do not establish the specific analytic procedures used by the investigators.

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:

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 All-cause Mortality at the Time of Pediatric Intensive Care Unit (PICU) Discharge, measured over Admission to PICU discharge, up to 120 days.

The primary endpoint was the count of participants who died from any cause between PICU admission and PICU discharge, with follow-up specified as up to 120 days. The registry describes it as overall mortality from admission to PICU discharge. For this binary endpoint, each participant contributes an outcome classified as death or no death within the specified period.

Mortality is an outcome that can be counted directly and compared across randomized groups. In this trial, the posted primary results report 15 deaths among 26 participants assigned to calfactant and 6 among 17 assigned to air placebo. The comparison is therefore about the observed proportion with the endpoint in each group, as well as the uncertainty around the estimated difference. Counts and group sizes are important together: the same number of events can imply different event proportions when the denominators differ.

The endpoint is tied to the PICU episode rather than an unrestricted period after discharge. It does not describe all later mortality, and the registry does not report longer-term follow-up for this outcome. The stated limit of up to 120 days defines the reported outcome window; it does not mean every participant was observed for that duration. The registry record does not report additional details about how discharge, transfers, or incomplete follow-up were handled in the analysis.

7. Results Posted in the Registry

• Calfactant: 57.7% (15/26) versus 35.3% (6/17) on control; risk difference 22.4 percentage points (95% CI -7.2 to 52.0), risk ratio 1.63 (0.79–3.37); unadjusted two-proportion z-test p = 0.151.

8. Statistical Interpretation

9. Statistical Methods Explained

A binary endpoint has two possible states for each participant. For this primary outcome, those states are death or no death by PICU discharge within the specified outcome window. The registry reports the number of participants with an event and the number in each group. These counts are the starting point for the comparison, while the group denominators indicate how many participants contributed to each arm’s reported result.

A risk difference compares the event proportions in two groups by subtracting one proportion from the other. Its sign depends on the direction in which the groups are ordered. In the posted comparison, the estimate is 0.224 for calfactant relative to placebo. The positive sign therefore denotes a higher event proportion in the calfactant group under this ordering. A difference of zero would correspond to equal event proportions; values below or above zero indicate opposite directions of difference. This statistical description does not by itself establish a treatment effect.

A confidence interval describes a range of estimates compatible with the observed data under the procedure used to calculate it. It gives information about precision as well as direction. The interval reported for the risk difference extends from -0.072 to 0.520 when shown to three decimal places. Because it includes zero and spans values on both sides, it does not pin down the direction or size of the underlying difference precisely. The registry record does not identify the confidence-interval method or state the confidence level, so those details should not be inferred.

The unadjusted p-value is 0.151. In general, a p-value measures how compatible observed data are with a null hypothesis under the test’s assumptions. It is not the probability that a treatment has no effect, and it does not measure clinical importance. “Unadjusted” indicates that the reported value is not adjusted for multiplicity in the posted comparison. The registry record does not report the test used, whether any covariates were included, or whether this analysis matches the protocol’s planned test.

Other effect measures can present the same two-group comparison on different scales. A risk ratio compares the event proportions as a ratio; an odds ratio compares the odds of an event. The posted risk ratio is 1.635, with an interval from 0.793 to 3.368. The posted odds ratio is 2.5, with an interval from 0.707 to 8.839. The different numerical scales are not interchangeable, and their interpretation depends on the measure. Both intervals are broad and include the value representing no relative difference. They should be read as alternative descriptions of uncertainty, not as independent findings.

Randomized allocation is intended to make assigned groups comparable on average, including with respect to factors that may affect outcomes. It does not guarantee that every characteristic will be balanced in a particular trial, especially when the enrolled sample is small. The registry identifies the allocation as randomized but does not report sequence generation, concealment procedures, stratification, or other randomization details. The description of quadruple masking also does not identify which groups of people were masked.

For count outcomes, over-dispersion is not the central issue in the same way it can be for repeated or rate-based measurements. In general, over-dispersion means that observed variability exceeds what a statistical model assumes. It can make standard errors too small if ignored. The primary endpoint is reported as participant counts with a binary event, and the registry record does not state that an over-dispersion adjustment was used or needed. More broadly, the record does not provide enough analytic detail to reconstruct the investigators’ full model or reproduce their primary analysis.

The registry lists four secondary outcomes, but their numerical results are not reported in the registry record. Without those results, it is not possible to describe their estimates or their uncertainty. Nor does the record explain whether the primary comparison was analyzed by assigned group, whether any participants were excluded from the analysis, or how missing outcome data were treated. These are important details for understanding the estimand and the strength of the inference, and they remain unreported in the registry record.

10. Confidence Intervals and Precision

The primary estimate is a risk difference of 0.224. The reported interval extends from -0.072 to 0.520 when rounded to three decimal places. That span is wide relative to the point estimate and includes zero. It therefore leaves considerable uncertainty about the direction and magnitude of the underlying difference. The endpoints also permit values on both sides of zero, rather than concentrating the interpretation on one direction.

The posted group counts help explain why precision is limited: the primary outcome was reported for 26 participants in the calfactant group and 17 in the placebo group, with 15 and 6 deaths, respectively. With relatively few participants and events, estimates of group differences can vary substantially across samples. This is a general statistical point, not a claim that the observed counts are inaccurate. The data describe the enrolled trial participants, while the interval reflects uncertainty in using those data to estimate a broader group contrast.

The risk-ratio interval, 0.793 to 3.368, and odds-ratio interval, 0.707 to 8.839, are also broad and include the respective null value of one. These measures express the comparison on relative rather than absolute scales. Their ranges reinforce that the registry results do not precisely determine the size or direction of the underlying contrast.

The registry record does not state the confidence level or method used for the intervals, so those properties cannot be evaluated from the record. Precision is distinct from statistical significance: an interval communicates plausible values under its calculation procedure, while the p-value addresses compatibility with a null hypothesis under a test. Neither removes uncertainty, and neither alone establishes the clinical importance of the observed result.

11. 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 assumptions. They are expressed as participants per arm, not as total events. 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 trial’s own original sample-size justification and design assumptions are not reported in the registry record.

For planning based on 100% of the observed effect, the illustration gives 77 participants per arm for 80% power and 103 participants per arm for 90% power. For planning based on 75% of the observed effect, it gives 136 participants per arm for 80% power and 182 participants per arm for 90% power. For planning based on 50% of the observed effect, it gives 302 participants per arm for 80% power and 403 participants per arm for 90% power.

In plain language, a power target describes the chance that a planned study will meet its statistical detection criterion if the effect assumed for planning is the true effect and the other planning assumptions hold. The 90% column uses a higher detection probability target than the 80% column, and therefore calls for more participants in these illustrations. Smaller assumed effects also require more participants, because a less pronounced difference is harder to distinguish from random variation.

These figures are not observed power for CALIPSO. They are hypothetical planning values tied to the observed effect and stated assumptions; they do not show that the completed trial had a particular chance of detecting an effect. They also should not be read as evidence that the original study was planned using those assumptions.

12. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.353; treatment proportion p₁ = 0.577; average p̄ = 0.465.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7054 = 1.3825.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6874 = 0.5785.
4. n = (1.3825 + 0.5785)² / (0.2240)² = 76.7, rounded up to 77 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
p0 <- 0.352941176470588                          # control proportion
p1 <- 0.576923076923077                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(999713)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 77 (80% power), 103 (90% power)
 75% of observed effect: n per arm = 136 (80% power), 182 (90% power)
 50% of observed effect: n per arm = 302 (80% power), 403 (90% power)
power.prop.test: 76.7 
Simulated power at n = 77 per arm: 0.789 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and four secondary outcomes. When several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiple testing. In general, multiplicity procedures can control that risk by adjusting thresholds or interpreting results within a prespecified hierarchy. The registry record does not report whether such a strategy was planned or used. The posted primary p-value is unadjusted, and no numerical secondary results are reported in the registry record.

Missing data can affect an analysis when outcome status is unavailable for some participants or when follow-up differs across groups. The registry record does not report whether any primary outcome data were missing, how missingness was defined, or what methods were used to address it. The posted group denominators and event counts are available, but they do not describe the handling of any participants outside those counts.

Analysis populations also matter. An intention-to-treat analysis generally compares participants according to randomized assignment, while other analysis sets may exclude or reclassify participants according to post-randomization events. These are general statistical distinctions. The registry record does not specify the analysis population used for the posted primary comparison, so it is not possible to label the result as intention-to-treat or to determine whether another population was used.

The record does not report an interim-analysis plan, stopping rules, a prespecified statistical analysis plan, or adjustment for covariates. It is not appropriate to infer any of these from the completed status or the existence of a p-value. These unreported details limit evaluation of how the analysis was specified before outcomes were known, and how the primary result relates to any other planned comparisons.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (57.7%), hypoxia (15.4%), renal failure (7.7%).

The registry’s serious adverse event entries report 15 affected participants among 26 at risk in the calfactant group and 7 among 17 at risk in the placebo group. The corresponding entries for other adverse events report 8 among 26 and 1 among 17. These are participant counts, not event rates calculated for comparison, and the record does not provide a statistical comparison or uncertainty estimates for them.

The most frequently listed serious terms are Death at 57.7%, Hypoxia at 15.4%, and Renal Failure at 7.7%. The registry record does not state the denominator or detailed coding rules for these term percentages, so they should be read as reported rather than reinterpreted as risks among all randomized participants.

The adverse-event entry reports 7 deaths in the placebo group, while the primary outcome entry reports 6 deaths in that group. The registry record does not explain this difference or whether the entries use different definitions or reporting windows. The two entries should therefore be kept distinct rather than treated as interchangeable. Serious adverse event listings describe safety reporting; they are not, by themselves, a causal comparison of treatment-related harms.

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

The results describe mortality by PICU discharge among participants randomized in CALIPSO. The posted primary outcome counts are 15 deaths among 26 participants assigned to calfactant and 6 among 17 assigned to air placebo. The estimated risk difference is 0.224, and its interval includes zero while extending substantially in both directions. The unadjusted p-value is 0.151. Taken together, these statistics describe an observed difference accompanied by considerable uncertainty.

The results do not establish that calfactant caused the observed difference, nor do they establish that the underlying difference is zero. The interval and small group sizes leave a range of possible contrasts compatible with the data. A non-significant p-value is not proof of equivalence, and a point estimate is not proof of a true effect. The registry findings are best read as estimates from this particular randomized sample.

The endpoint covers mortality through PICU discharge, up to 120 days. It does not answer questions about mortality after discharge or outcomes beyond that period. Although oxygenation, ventilator-free days and duration of stay are listed as secondary outcomes, their numerical results are not reported in the registry record. Thus the posted mortality comparison cannot be combined with those other outcomes to form a broader quantitative assessment.

The findings should not be generalized automatically to every child with acute lung injury or to settings not described by the registry’s population. The enrolled sample included 43 participants and was drawn from the pediatric oncology and HSCT context specified in the trial record. The registry record does not report sufficient detail about eligibility criteria, missing outcomes, analysis populations or original design assumptions to resolve all questions about applicability and analysis.

16. Why This Trial Matters Statistically

This trial raises statistical issues common to randomized studies in small, clinically defined populations. CALIPSO enrolled 43 participants, with 26 in the calfactant group and 17 in the placebo group for the primary outcome. The context is pediatric acute lung injury among patients with leukemia, lymphoma or hematopoietic stem cell transplantation. Such a defined population can be difficult to study in large numbers, but small samples make estimates particularly sensitive to the observed event counts.

The primary result illustrates why effect estimates and uncertainty should be read together. The risk-difference point estimate is 0.224, but its interval includes zero and extends to 0.520 at the upper end when expressed to three decimal places. The p-value of 0.151 does not resolve the uncertainty, and the alternative relative measures also have broad intervals. Looking only at the point estimate, or only at a thresholded p-value, would omit important information about precision.

The registry also distinguishes primary from secondary outcomes in the trial’s aims. Numerical secondary findings are not reported, and the primary p-value is unadjusted. This makes multiplicity and selective emphasis relevant considerations, while leaving the exact planned analysis unknown. The posted sample-size illustration further shows, as a general planning principle, that smaller target effects require larger samples; it is not evidence of the original design or of achieved power.

Finally, the record illustrates the importance of careful endpoint and safety-data reading. The primary mortality count and adverse-event death count differ for placebo, and the record does not explain why. Keeping registry entries distinct and noting what is unreported avoids implying a reconciliation that the record does not support.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary outcome is based on a total enrollment of 43 and the reported group sizes are 26 and 17. The resulting risk-difference interval is broad, so the estimate is not precise. The record does not report the original sample-size justification, and the planning illustration cannot establish whether the trial was designed to detect the effect observed.

Several details needed to assess analysis quality are not reported in the registry record: the randomization procedure, the people covered by quadruple masking, the analysis population, missing-data methods, statistical test, confidence-interval method, interim analyses, and prespecified multiplicity strategy. The registry also does not state the confidence level for the interval. These gaps prevent a full assessment of the planned-versus-posted analysis.

The primary endpoint is limited to PICU discharge and a timeframe of up to 120 days. Longer-term outcomes are not reported. Four secondary outcomes are listed, but their numerical results are not reported in the registry record, limiting interpretation of the broader clinical aims.

There is also a difference between the placebo death count in the primary outcome entry and the adverse-event entry: 6 versus 7. The record does not explain the difference, so the entries cannot be reconciled from the information reported. These limitations do not alter the posted counts, but they constrain interpretation of the estimates and their relevance beyond this trial.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: CALIPSO: Calfactant for Acute Lung Injury in Pediatric Stem Cell Transplant and Oncology Patients — NCT00999713.
• Registry record last updated 2018-03-16; status last verified 2018-02.
• Results first posted 2018-03-16.
• 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.

21. Record Summary

CALIPSO (NCT00999713) was a completed randomized, parallel-group phase 2/3 trial sponsored by Milton S. Hershey Medical Center. It enrolled 43 participants and compared endotracheal calfactant with endotracheal air placebo in pediatric patients with acute lung injury in an oncology and HSCT setting. The registry lists quadruple masking.

The primary endpoint was all-cause mortality from PICU admission to discharge, up to 120 days. The posted counts were 15 deaths among 26 calfactant participants and 6 among 17 placebo participants. The risk difference was 0.224, with a broad interval spanning zero, and the unadjusted p-value was 0.151. Four secondary outcomes are listed, but their numerical results are not reported in the registry record. Important details about the original sample-size justification and analysis methods are also not reported.