Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement (NCT00448864), a randomized phase 2 study. The primary outcome is Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively.

2. Clinical Question

The study’s primary objective was to assess the efficacy and safety of two ecallantide dose levels relative to placebo in reducing blood loss following cardiopulmonary bypass. The endpoint was postoperative chest tube drainage. This is a measure of blood leaving through the surgical drainage system, rather than a direct measure of every source of blood loss.

The stated secondary objectives included comparing participants treated with either ecallantide dose pooled together against placebo, and comparing the high-dose group with the low-dose group. The registry’s posted primary comparisons instead present each dose group separately against placebo. Other stated secondary objectives were to evaluate pharmacokinetics and antibody formation. The posted secondary outcomes include chest tube drainage at 24 hours, treatment-emergent adverse events, and pharmacokinetics. Antibody formation results are not reported in the registry record.

The trial record reports enrollment of 75 and status as terminated. The reason for termination is not reported in the registry record. The record identifies the population and comparison, but it does not give a complete account of eligibility criteria or all features of treatment administration. Conclusions from the posted measurements therefore concern the recorded groups and outcomes, rather than a wider population or outcomes that were not reported.

3. Trial Design

This was a phase 2, randomized, parallel-group study with quadruple masking. The three posted groups were ecallantide at a low dose, ecallantide at a high dose, and placebo. The registry lists enrollment of 75. The primary outcome data are reported for 26 participants in the low-dose group, 25 in the high-dose group, and 18 in the placebo group. The primary outcome population is described as participants who received at least 1 dose of study drug.

Participants were undergoing primary coronary artery bypass grafting, single valve repair, or single valve replacement requiring cardiopulmonary bypass. The primary outcome timeframe was up to 12 hours after admission to the intensive care unit. Drainage was measured during the first 12 hours postoperatively or until chest tube removal, whichever came first. The posted secondary drainage outcome covers up to 24 hours after admission to the intensive care unit.

The registry describes staged intravenous infusions for the ecallantide and placebo groups. The low-dose description states a maximum of 15 milligrams, while the high-dose description states a maximum of 91 mg. The full treatment descriptions are incomplete in the registry record, so details beyond the text recorded there are not available. Allocation concealment procedures and the exact masking roles are not reported in the registry record.

The registry lists a randomized allocation and parallel model, but the sequence-generation method and procedures for maintaining allocation concealment are not reported in the registry record. The study is marked terminated; the reason for termination and whether it was related to recruitment, safety, or another consideration are not reported in the registry record. The trial’s original sample-size assumptions, planned analysis methods, and any interim analyses are also not reported in the registry record. The posted planning illustrations are separate calculations based on observed effects, not documentation of the trial’s original design.

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: All participants who received at least 1 dose of study drug.

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: Randomized participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively, measured over Up to 12 hours post admission to intensive care unit (ICU).

The primary endpoint is cumulative chest tube drainage, expressed in milliliters and summarized as a mean with a standard deviation for each treatment group. It covers the first 12 hours postoperatively or ends when the chest tube is removed, whichever comes first. The registry gives the timeframe as up to 12 hours after admission to the intensive care unit. The outcome population consists of participants who received at least 1 dose of study drug.

Chest tube drainage is used as a measurable postoperative indicator of blood loss following cardiac surgery with cardiopulmonary bypass. It captures fluid collected through the chest drainage system during a defined period. It does not by itself describe all bleeding, transfusions, reoperations, or other clinical consequences; those outcomes should not be inferred from the drainage measurement. The registry separately lists adverse events and a 24-hour drainage outcome.

A group mean describes the average measured drainage in that group, while the standard deviation describes how dispersed individual measurements are around that average. A lower mean indicates less average drainage in the posted group summaries, but the mean alone does not show how much individual participants’ outcomes overlap. The comparison estimates and intervals are useful for assessing the uncertainty around differences between group means. In this trial, the intervals are broad, so the group averages should be read alongside the uncertainty rather than as precise estimates of an effect.

The measurement window is important to interpretation: the outcome is not a total over an identical period for every participant because drainage could be counted only until chest tube removal when that occurred first. The registry does not report how chest tube removal decisions were made or how the analysis handled different observation durations.

7. Results Posted in the Registry

• Ecallantide - Low Dose Regimen: mean 729.90 versus 1,401 on control; difference -670.80 (95% CI -1,326 to -15.74), standardized effect d = -0.72; z-test p = 0.045.
• Ecallantide - High Dose Regimen: mean 935.80 versus 1,401 on control; difference -464.90 (95% CI -1,129 to 199.57), standardized effect d = -0.48; z-test p = 0.170.

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.

Cumulative Chest Tube Drainage at 24 Hours Postoperatively

• 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:
  • Ecallantide - Low Dose Regimen: mean 82.90 versus 225.30 on control; difference -142.40 (95% CI -353.92 to 69.12), standardized effect d = -0.48; z-test p = 0.187.
  • Ecallantide - High Dose Regimen: mean 149.80 versus 225.30 on control; difference -75.50 (95% CI -291.37 to 140.37), standardized effect d = -0.24; z-test p = 0.493.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ecallantide - Low Dose Regimen and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ecallantide - High Dose Regimen and the control. The interval gives the range of effects that remain compatible with the data.

Pharmacokinetics: Area Under the Concentration Time Curve

• 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:
  • Ecallantide - High Dose Regimen: mean 13.60 versus 1.39 on control; difference 12.21 (95% CI 10.79 to 13.63), standardized effect d = 4.81; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Ecallantide - High Dose Regimen than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes offer context but do not settle the primary question. The 24-hour drainage summaries have the same broad directional pattern as the primary summaries, with lower group means for ecallantide than placebo, while the recalculated intervals for both dose comparisons include zero. The pharmacokinetic outcome separates the dose groups, but drug exposure is not itself a measure of postoperative blood loss or a patient-centered clinical outcome.

Treatment-emergent adverse events are also listed as a secondary outcome, and the registry provides counts for serious and other adverse events by group. These descriptive safety summaries complement the efficacy measurements but do not establish whether observed events were caused by treatment. The registry’s stated secondary objectives included antibody formation, but results for that objective are not reported in the registry record.

The secondary drainage findings do not materially resolve the uncertainty in the primary comparison. A pattern of lower means across measurement windows can be descriptively consistent, yet intervals that include zero leave substantial uncertainty about the size and direction of the underlying differences. Pharmacokinetic differences show that the dose groups had different measured exposure, but they cannot substitute for evidence about the clinical endpoint.

Unadjusted secondary results carry less weight when multiple outcomes and comparisons are examined. Without a reported multiplicity strategy, the record does not show whether any result was selected from a wider set of tests or how the overall chance of false-positive findings was managed. The registry also lists no reported analyses for these outcomes. These results are therefore best treated as supportive descriptive information and as prompts for further evaluation, rather than as independent confirmation of the primary finding.

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

• Cumulative Chest Tube Drainage at 24 Hours Postoperatively
• Number of Participants With Treatment-emergent Adverse Events
• Pharmacokinetics: Area Under the Concentration Time Curve

9. Statistical Interpretation

10. Statistical Methods Explained

The posted outcome is a continuous measurement, summarized by a mean and standard deviation for each arm. The mean is the arithmetic average of the recorded drainage values. The standard deviation describes how spread out those values are around the average. When individual measurements vary widely, the group mean can be estimated less precisely, especially when the group contains relatively few observations.

What does a mean difference describe?

The comparison is expressed as an unadjusted mean difference between an ecallantide group and placebo. Negative estimates in the posted comparisons mean that the ecallantide group’s reported mean was lower than the placebo mean. The estimate is an absolute difference in milliliters, not a percentage change or a relative risk. It summarizes the observed contrast in group averages and does not describe the difference for every participant.

The estimates are recalculated from the posted arm-level summaries. The registry record does not include a reported inferential analysis for the primary outcome. This distinction matters: the recalculated comparisons can help readers understand the posted means and their uncertainty, but they are not a substitute for a prespecified sponsor analysis. The discrepancy flag is false, so there is no recorded conflict requiring a sponsor result to take precedence.

How should an interval be read?

In general, a confidence interval gives a range of values compatible with the data under the assumptions of the calculation. A narrower interval indicates greater precision; a wider interval indicates less precision. For a difference between means, zero represents no difference between the group means. An interval that includes zero is compatible with no mean difference, while an interval that excludes zero indicates that zero is outside that particular interval. Neither feature establishes clinical importance on its own. The confidence level and full interval calculation method are not reported in the registry record.

The low-dose interval runs from -1326.0 to -15.74 milliliters, whereas the high-dose interval runs from -1129.0 to 199.6 milliliters. The first lies below zero, and the second includes zero. These are unadjusted recalculated intervals; the record does not report whether the trial’s own analysis used the same method, or whether it used adjusted analyses.

What does a p value contribute?

In general, a p value describes how incompatible the observed data are with a specified null model, assuming that model and the calculation’s assumptions are appropriate. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The unadjusted p values are 0.045 for the low-dose comparison and 0.17 for the high-dose comparison. The registry’s original significance threshold and testing procedure are not reported. The 0.05 level appears in the planning illustration assumptions, but that does not establish the trial’s own inferential threshold.

Because the posted p values are unadjusted, they do not account for the collection of comparisons across doses and outcomes. When many hypotheses are examined, the chance of at least one apparently notable result can increase. A multiplicity adjustment or a prespecified hierarchy can address this issue, but the registry does not report such a method. The p values therefore require cautious interpretation, especially alongside the limited group sizes and broad intervals.

Why can over-dispersion matter?

General statistical explanation: over-dispersion means that observed variation is greater than a model’s assumptions allow. If a method assumes more uniform data than are actually present, standard errors may be too small and intervals too narrow. The posted standard deviations show substantial variability, including especially wide spread in the placebo group. The registry does not report a model-based assessment of over-dispersion or a particular method for handling it. These summaries support caution about treating a simple mean comparison as a complete account of the data distribution.

What analyses are documented?

The registry provides group means, standard deviations, and sample sizes, along with recalculated unadjusted comparisons. It lists no reported analyses for the primary or posted secondary outcomes. The protocol’s analysis population beyond the primary outcome description, handling of missing measurements, covariate adjustment, and treatment of participants with incomplete follow-up are not reported in the registry record. Randomization supports a controlled comparison in principle, but it does not remove uncertainty arising from small groups, missing information, or analysis choices that are not documented.

The posted planning calculations use a normal approximation and assume equal allocation between two arms, a two-sided significance level of 0.05, and an effect set to a stated fraction of the observed effect. Those are assumptions for the planning illustration only. The trial’s own design assumptions are not reported in the registry record. The planning output should not be used as evidence that the trial had a particular probability of detecting an effect.

11. Confidence Intervals and Precision

The primary mean-difference intervals are broad. For the low-dose comparison, the recalculated difference is -670.8 milliliters, with an interval from -1326.0 to -15.74. The interval excludes zero, but its endpoints cover a wide range of possible differences. For the high-dose comparison, the estimate is -464.9 milliliters, with an interval from -1129.0 to 199.6. That interval includes zero and permits both lower and higher average drainage in the ecallantide group than in placebo.

These intervals express uncertainty around group-average contrasts, not the range of individual outcomes. The standard deviations indicate considerable variation within arms, and the arm sizes are limited. Both features contribute to the need for caution when interpreting an estimated mean difference. The interval does not show that every value within its limits is equally plausible, and it does not identify which value is clinically important.

General statistical explanation: an interval that excludes zero is evidence against a zero difference under the assumptions used to construct that interval. It is not a guarantee that the effect is real, important, or reproducible. An interval that includes zero does not prove there is no effect; it can reflect imprecision as well as a small underlying difference. The registry does not report the confidence level or calculation method for these intervals, and the comparisons are unadjusted recalculations rather than reported sponsor analyses.

The low-dose interval’s upper endpoint is close to zero, while the high-dose interval spans zero. That contrast should not be treated as evidence that the dose groups differ from each other: both intervals compare an ecallantide dose with placebo, and no direct high-dose versus low-dose analysis is reported in the registry record. Precision is therefore limited both for estimating each placebo contrast and for answering the separate question of whether dose levels differ.

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 illustrations are planning calculations, not a record of the trial’s original design. For continuous outcomes such as drainage, the figures are participants per arm, not total participants or total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to 100%, 75%, or 50% of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm that would correspond to 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 number per arm for a higher target chance of detection. These are design targets, not probabilities calculated from the completed trial.

The scenarios use fractions of the observed effect. If a future study aims to detect a smaller effect, it generally needs more participants to distinguish that effect from random variation under otherwise similar assumptions. The planning entries illustrate this pattern: the figures rise as the assumed effect is reduced from the full observed effect to 75% and then 50%. The required number also differs between the low-dose and high-dose comparisons because the observed effects and variability differ.

These numbers are not observed power. Observed power calculated from the final estimate would not resolve the uncertainty in the actual results; the confidence intervals and estimates are more informative for that purpose. The planning calculations also assume two-arm comparisons and equal allocation, so they do not reproduce the trial’s three-group design or establish what design choices were made before enrollment.

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 = -670.800; pooled standard deviation σ = 934.147.
2. n = 2 × (1.96 + 0.842)² × 934.147² / -670.800² = 30.4, rounded up to 31 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 <- -670.8                      # observed difference in means
sigma <- 934.14655861711                     # 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(448864)
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 = 31 (80% power), 41 (90% power)
 75% of observed effect: n per arm = 55 (80% power), 73 (90% power)
 50% of observed effect: n per arm = 122 (80% power), 164 (90% power)
power.t.test: 31.4 
Simulated power at n = 31 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. Multiplicity, Missing Data and Analysis Populations

The registry lists several treatment comparisons and outcomes, including two ecallantide doses versus placebo, a stated objective to compare the two doses, postoperative drainage at more than one timeframe, adverse events, and pharmacokinetic measurements. Testing multiple outcomes can make isolated unadjusted results harder to interpret. The registry does not report a multiplicity adjustment, testing hierarchy, primary-versus-secondary testing sequence, or other strategy for controlling the overall false-positive risk. The unadjusted comparisons should therefore not be interpreted as if a trial-wide testing plan were documented.

The record contains no reported analyses for the primary or secondary outcomes. It does not report whether the statistical analysis plan was finalized before unmasking, what covariates were considered, how deviations from assigned treatment were handled, or how incomplete measurements were treated. The registry identifies the primary outcome population as participants who received at least 1 dose of study drug, but does not report whether an intention-to-treat analysis or another population was used for inferential analyses.

Missing-data methods and the extent of missing primary outcome measurements are not reported in the registry record. The endpoint could end at chest tube removal before the stated observation window, but the record does not explain how differing observation periods or early removals entered the analysis. It also does not report whether any sensitivity analyses assessed the consequences of missing measurements or varying follow-up.

The original sample-size justification, planned interim analyses, and prespecified statistical thresholds are not reported in the registry record. The planning illustration’s significance level is not evidence of the trial’s own testing threshold. The trial is marked terminated, but the reason for termination is not reported. Without these details, it is difficult to assess whether the posted results reflect the planned analyses or how the study’s conduct affected the amount of information available.

15. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: haemorrhage (16.7%), post procedural haemorrhage (8.0%), wound infection (5.6%), dehydration (5.6%), convulsion (5.6%).

The registry reports serious adverse events affecting 9 participants in the low-dose group, 4 in the high-dose group, and 7 in the placebo group. The corresponding groups at risk were 26, 25, and 18. Other adverse events are reported for 25 participants in the low-dose group, 23 in the high-dose group, and 18 in the placebo group. These are descriptive counts; they do not establish that an event was caused by ecallantide or that the groups differ in safety.

The registry lists serious event terms including haemorrhage, post procedural haemorrhage, wound infection, dehydration, convulsion, and syncope, with the percentages recorded for those terms. The record does not provide enough information in this summary to assign every listed term to a treatment group or to establish the relationship of each event to treatment. Death counts are not reported in the registry record.

Safety comparisons require particular caution because the groups are small and the registry does not report a comparative safety analysis, event definitions, severity grading beyond the serious-event classification, or attribution procedures. Counts alone do not describe event timing, recurrence, duration, or clinical consequences. The registry’s adverse-event data should be read as a descriptive record of reported events, not as a definitive estimate of comparative risk.

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

The posted primary summaries show lower mean chest tube drainage in both ecallantide groups than in placebo. The low-dose comparison has an unadjusted recalculated interval that excludes zero, while the high-dose interval includes zero. This is a description of the observed group means and their uncertainty, not a determination that ecallantide reduces blood loss or that it does not.

The uncertainty is substantial. The intervals are broad, the group standard deviations indicate marked variability, and the treatment groups are limited in size. The observed estimates leave room for materially different underlying mean differences. In addition, the posted comparisons are unadjusted recalculations, and the registry does not report the sponsor’s inferential analyses or the trial’s analysis plan. The nominal pattern should not be presented as a definitive treatment effect.

The data also do not establish a dose-response relationship. Although the low-dose group has a lower posted mean than the high-dose group, the registry does not report a direct statistical comparison between those groups. Separate comparisons against placebo cannot determine whether the two ecallantide regimens differ from one another.

The endpoint captures chest tube drainage during a defined postoperative period. It does not by itself answer questions about all blood loss, transfusion requirements, recovery, or other outcomes not included in the posted results. The secondary measures provide additional context, but unadjusted secondary findings and the pharmacokinetic outcome do not replace a clear, adequately precise primary comparison.

The study is marked terminated, and the reason is not reported in the registry record. The trial’s original sample-size assumptions, handling of missing data, multiplicity approach, and interim analyses are also not reported. These gaps limit assessment of how the study was planned and how fully the observed data address its objectives. The results can inform statistical discussion of variability, uncertainty, and outcome selection, but the registry record alone does not establish a clinical conclusion.

17. Why This Trial Matters Statistically

This trial illustrates how the direction of a point estimate and the strength of the evidence about that estimate are different questions. Both ecallantide group means are below the placebo mean for the primary drainage measure, but the precision differs: one unadjusted interval excludes zero and the other includes it. Neither pattern by itself answers whether a difference is clinically important or reproducible.

The record also shows why the scale and dispersion of an outcome matter. Chest tube drainage is measured continuously, and the posted standard deviations are substantial. A group mean can summarize the data clearly while concealing considerable variation among participants. Intervals around the differences help show how that variation and the available group sizes limit precision.

A further statistical lesson is the distinction between a trial’s reported analysis and a recalculation from summary statistics. The registry gives group means and standard deviations but lists no reported analyses. Recalculated comparisons offer a transparent way to examine the summaries, yet they cannot reveal whether a prespecified analysis differed, how missing measurements were handled, or how multiple outcomes were treated.

The trial also highlights the difference between planning illustrations and trial design. The displayed sample-size calculations use specified assumptions based on observed effects; they do not document the assumptions used to plan enrollment. This distinction is important when interpreting small studies and when considering what future research might need to estimate effects more precisely.

Finally, the several outcomes serve different purposes. Drainage measures a postoperative clinical quantity, adverse-event counts describe safety observations, and pharmacokinetics characterizes drug exposure. Keeping those roles distinct prevents a result on one measure from being treated as proof about another. The incomplete analysis and design reporting makes that separation especially important.

18. 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 comparisons are recalculated from posted summary statistics, while the registry lists no reported primary analyses. The full statistical analysis plan, the confidence-interval method, the original significance threshold, and any covariate adjustment are not reported. These omissions prevent a direct assessment of how the recalculations compare with the trial’s prespecified analysis.

The observed group sizes are limited, and the standard deviations are large. This combination contributes to wide uncertainty around the mean differences. The registry does not report the distribution of individual drainage values, so it is not possible to judge from these summaries whether unusual values or a non-normal distribution strongly influenced the means.

The primary endpoint observation period could end when the chest tube was removed, even if that occurred before the end of the stated period. The record does not report removal criteria, individual observation durations, missing outcome counts, or the method used to account for varying measurement time. These details could affect interpretation of a cumulative drainage measure.

The study’s status is terminated, but the reason is not reported. The record does not explain whether the trial stopped as planned or for another reason. It also does not report the original sample-size justification, interim monitoring, or how enrollment and follow-up compared with the original plan. The posted enrollment figure should not be used to infer the reason for termination or the adequacy of the original design.

Other limitations include the absence of a reported direct comparison between the ecallantide dose groups, no stated multiplicity strategy, and incomplete reporting of secondary objectives such as antibody formation. The registry’s intervention descriptions are also incomplete. Consequently, readers cannot fully reconstruct treatment administration or determine how the study addressed all of its stated objectives from this record alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement — NCT00448864.
• Registry record last updated 2019-06-25; status last verified 2019-06.
• Results first posted 2015-07-08.
• 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.

22. Record Summary

The registry record describes KALAHARI-1, a randomized, quadruple-masked, parallel-group phase 2 study of low-dose ecallantide, high-dose ecallantide, and placebo in participants undergoing primary coronary artery bypass grafting or single valve surgery requiring cardiopulmonary bypass. The registry lists enrollment of 75 and marks the study terminated.

The primary outcome was mean chest tube drainage during the first 12 postoperative hours or until chest tube removal, whichever came first. The posted means were 729.9 milliliters for low-dose ecallantide, 935.8 milliliters for high-dose ecallantide, and 1401.0 milliliters for placebo. The unadjusted recalculated comparison intervals are broad, and the registry lists no reported analyses.

Secondary information includes 24-hour drainage, adverse events, and pharmacokinetics. The registry does not report the reason for termination, the trial’s original sample-size assumptions, its analysis plan, missing-data methods, or multiplicity procedures. The record therefore supports cautious description of the posted summaries, not a definitive conclusion about treatment effects.