This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety Study of Kedbumin 25% Versus Normal Saline in the Treatment of Post-Surgical Hypovolemia in Pediatric Patients (NCT01531803), a randomized phase 4 study. The primary outcome is Incidence, Severity, and Seriousness of Fluid Overload and Edema (Pulmonary Portal or Systemic) and/or Other Complications Secondary to Fluid Resuscitation With Kedbumin 25% Compared to Normal Saline..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01531803 |
| Phase | Phase 4 |
| Condition | Hypovolemia |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Kedrion S.p.A. |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric patients undergoing major elective surgery who developed post-surgical hypovolemia were the intended population. The registry describes an intended age range from 0 days to 12 years and cardiac, abdominal, orthopedic, or transplant surgery. The study was prematurely stopped, and the reported enrollment was 3 participants.
Intervention
Kedbumin 25% was administered by intravenous infusion. The registry describes a dose of 0.5 to 1g/kg body weight, or 2 to 4 mL/kg. The treatment duration description is incomplete in the registry record.
Comparator
The comparator was normal saline solution, described as 0.9% saline given by intravenous infusion at 10 to 20 mL/kg as appropriate to clinical status and response to treatment.
Primary question
The primary safety question concerned the incidence, severity, and seriousness of fluid overload, edema, and other complications secondary to fluid resuscitation, assessed over 3 days. The posted results record zero participants with the primary outcome in each arm, but the very small enrollment and non-estimable two-arm comparison limit what can be inferred from that observation.
3. Trial Design
The registry describes a prospective, randomized, multicenter, controlled, open-label study of Kedbumin 25% compared with normal saline in pediatric patients with post-surgical hypovolemia. The phase is listed as Phase 4. Masking is listed as none. Although the record identifies random allocation, the design model is listed as single group; this classification does not align neatly with the two named treatment arms and the randomized, controlled description. The exact allocation procedure and the reason for this model classification are not reported in the registry record.
The planned study population was at least 60 male and female pediatric participants aged 0 days to 12 years, with an approximately equal number in three specified age cohorts. The brief summary describes approximately 5 surgical and pediatric intensive care units in the US and a planned study period of 19 months. These are planning descriptions, not the enrollment or conduct reported in the results. Actual enrollment was 3, and the study status is terminated. The primary outcome population note says the study was prematurely stopped.
The listed start date is 2015-02-05, and the primary completion date is 2015-07-15. The registry lists 3 outcome measures, including the primary safety endpoint and secondary outcomes concerning resolution of hypovolemia and adverse events. Two secondary outcomes are posted. The registry record does not report an analysis plan, the reasons for termination, the actual number of participating sites, or the timing and process used to assign participants to treatment.
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
| Stage | Kedbumin 25% | Normal Saline Solution |
|---|---|---|
| STARTED | 1 | 2 |
| COMPLETED | 1 | 2 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The study has been prematurely stopped.
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: This study has been prematurely stopped. Only 3 participants have been enrolled.
| Characteristic | Unit | Kedbumin 25% | Normal Saline Solution | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 2 | 3 | |
| Age, Categorical: <=18 years | Participants | 1 | 2 | 3 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 2 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence, Severity, and Seriousness of Fluid Overload and Edema (Pulmonary Portal or Systemic) and/or Other Complications Secondary to Fluid Resuscitation With Kedbumin 25% Compared to Normal Saline., measured over 3 days.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with fluid overload, edema, or other complications considered secondary to fluid resuscitation. It covers incidence, severity, and seriousness, with assessment over 3 days. The endpoint combines clinical signs and measurements: pulmonary rales, specified chest X-ray or Doppler findings, oxygenation measures, changes in body weight relative to preoperative weight, and physical examination for edema. The registry also says safety measurements were to be collected, reviewed, and recorded until hemodynamic stability was achieved.
This type of endpoint is used to describe safety events that may arise during or following fluid resuscitation. Combining clinical findings can capture different manifestations of fluid overload and edema, while recording severity and seriousness distinguishes event occurrence from its clinical classification. The registry does not report how findings across the listed criteria were combined into a participant-level outcome, how disagreements in assessment were handled, or whether all criteria had to be assessed for each participant. Those operational details are not reported in the registry record.
The posted primary results are counts of participants: 0 of 1 in the Kedbumin 25% arm and 0 of 2 in the normal saline arm. With only 3 participants enrolled, these counts describe the observed participants but provide little information about how often such outcomes might occur in a broader population. The comparison is not estimable from the posted binary endpoint results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports no participants meeting the primary endpoint in either arm: 0 of 1 assigned to Kedbumin 25% and 0 of 2 assigned to normal saline. This is a description of the events recorded among the 3 enrolled participants. It is not evidence that the treatments have the same safety profile, and it does not establish that the endpoint cannot occur with either treatment.
The primary comparison is not estimable from these results. A two-arm binary comparison needs enough observed information to estimate a contrast with useful precision. When neither arm has a recorded primary event and the total enrollment is very small, the posted counts do not provide a stable estimate of the difference between treatment groups. The registry identifies the binary comparison as not estimable. No treatment-effect estimate, confidence interval, or p-value for this primary comparison is reported in the registry record.
Precision is central to interpretation. A confidence interval, when available, describes a range of values compatible with the data under the statistical model; a narrow interval indicates greater precision and a wide interval indicates substantial uncertainty. No interval is reported for the primary comparison, so the data do not quantify uncertainty as an estimated range. The small number of participants itself is an important limitation: an event that was not observed in a few participants may still occur in a larger group. This is a general statistical point, not a prediction about either treatment.
The study was prematurely stopped, and the reported enrollment of 3 is far below the intended enrollment of at least 60 described in the brief summary. The registry does not report the reason for stopping, whether recruitment or follow-up differed from plan, or whether the available participants represent the intended population. Without those details, the posted results cannot clarify how the early termination affected the study beyond the limited amount of information available.
The secondary outcomes concern resolution of hypovolemia with fluid resuscitation and hemodynamic stability within 72 hours, and the incidence, severity, and seriousness of expected and unexpected adverse events. Two secondary outcomes are posted, but no secondary statistical analyses are listed. Consequently, the registry record does not provide a basis for drawing comparative conclusions about those outcomes. The adverse-event counts should likewise be read as descriptions of this small group, not as reliable estimates of comparative risk.
9. Statistical Methods Explained
What a binary endpoint represents. The primary endpoint is reported as a count of participants with an event. For a binary outcome, each participant is classified as having or not having the event under the endpoint definition. The count is interpretable only in relation to the number of participants assessed in each arm. Here the registry reports zero primary events among 1 participant in the Kedbumin 25% arm and zero among 2 participants in the normal saline arm. Those counts are the observed results; they do not, by themselves, establish a population event rate or a treatment difference.
Why the comparison is not estimable. A comparative estimate summarizes how the outcome differs between treatment groups. Statistical estimation relies on observed events and non-events in the groups, together with the numbers assessed. With no primary events recorded and very few participants, the comparison does not yield a useful estimate of a between-arm contrast. The registry marks the binary two-arm comparison as not estimable. Accordingly, no recalculated comparison, interval estimate, or hypothesis-test result is presented. In general, a method cannot create information about an event pattern that the observed data do not contain.
Confidence intervals and precision. In general, a confidence interval expresses uncertainty around an estimated quantity under a specified statistical method. It is not a guarantee that the true value lies within the particular interval, nor does it correct for limitations in study design or data collection. A confidence interval for a treatment contrast would help show how much precision the observed results provide. The primary comparison has no reported interval because it is not estimable from the posted binary results. There is therefore no numerical range with which to judge the precision of a comparative effect.
Tests and p-values. In general, a p-value describes how incompatible the observed data are with a specified null hypothesis under the assumptions of a test. It does not measure the probability that a treatment is effective or safe, and it does not measure the size or importance of an effect. The registry reports no primary comparison p-value. With the comparison not estimable, a p-value would not resolve the lack of information in the observed counts. The registry record does not report the statistical test that would have been used under other data conditions.
Planning illustrations are not trial results. Sample-size calculations can illustrate how many participants per arm might be needed to detect an assumed effect under stated design assumptions. Such illustrations depend on the target effect, significance level, allocation, and statistical approximation. The registry describes an illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. These are planning assumptions, not evidence of the trial’s planned sample-size justification. Because the primary comparison is not estimable, an observed-effect planning illustration cannot supply a meaningful comparison for this endpoint. Any sample-size calculation is a planning illustration, not observed power and not a result from the trial.
Over-dispersion and model choice. General statistical models sometimes account for over-dispersion, which occurs when outcome variability exceeds what a simpler model assumes. This issue is more relevant to outcomes with counts or repeated observations than to a single participant-level binary endpoint. The primary outcome is listed as a participant count, and the registry does not report a model, an over-dispersion assessment, or a plan for repeated measurements. It would therefore be inappropriate to infer that such methods were used.
Randomization and open-label conduct. Randomization is intended, in general, to reduce systematic differences between groups by assigning participants through a chance-based process. The registry identifies the study as randomized and controlled, but does not report the sequence-generation method, concealment procedures, or details of implementation. Masking is listed as none, indicating an open-label design in the record. The registry does not describe whether outcome assessors were blinded. These omissions matter when evaluating how assignment and outcome assessment may affect comparability, but they do not establish that any particular bias occurred.
How to interpret the posted counts. The primary results are descriptive counts for the participants recorded in each arm. They are not adjusted estimates, and the registry reports no analyses for the primary outcome. The primary endpoint description includes several clinical measures and criteria, but the record does not explain how those components were combined, whether every participant had complete measurements, or how missing component values were handled. Those details are necessary for a full assessment of endpoint construction and analysis. Without them, interpretation should remain close to the reported counts and the registry’s note that the study stopped prematurely.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Kedbumin 25% | 1 | 0 | 0.0% | 0.0% to 97.5% | 0.0% to 79.3% | 1.3% to 84.2% |
| Normal Saline Solution | 2 | 0 | 0.0% | 0.0% to 84.2% | 0.0% to 65.8% | 0.8% to 70.8% |
R code and output
arm <- c("Kedbumin 25%", "Normal Saline Solution")
n <- c(1, 2)
events <- c(0, 0)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Kedbumin 25% 1 0 0.0 0.0 97.5 0.0 79.3 1.3 84.2
ARM Normal Saline Solution 2 0 0.0 0.0 84.2 0.0 65.8 0.8 70.811. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and two posted secondary outcomes. It does not report a multiplicity plan describing how statistical testing across outcomes would be controlled or interpreted. Multiplicity is a general concern when several outcomes are examined: conducting multiple tests can increase the chance of finding an apparently notable result by chance. No claim about the presence or absence of such a problem can be made from this record, because no analysis plan or secondary statistical results are listed.
The registry reports 0 primary events in each arm, but does not give a participant-level accounting of missing outcome data, exclusions, or the number assessed at each time point. The primary outcome population note states that the study was prematurely stopped. The registry does not describe an intention-to-treat population, a per-protocol population, or another analysis population, and it does not report a missing-data method. It is therefore unclear from the registry record how incomplete measurements, if any, were treated.
The planned study population and the final enrollment differ substantially: the brief summary describes at least 60 participants, while the reported enrollment is 3. This limits the amount of information available for both the primary and secondary outcomes. The reasons for termination, recruitment experience, follow-up completion, and any deviations from the planned population are not reported in the registry record. These gaps prevent a fuller assessment of how the stopped study was analyzed and which participants contributed to each posted result.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Kedbumin 25% | 0 | 1 | 0.0% |
| Normal Saline Solution | 0 | 2 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Kedbumin 25% | 0 of 1 |
| Normal Saline Solution | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Kedbumin 25% | Normal Saline Solution |
|---|---|---|---|
| Superficial Wound Infection | Skin and subcutaneous tissue disorders | 0 of 1 | 1 of 2 |
The serious adverse-event counts show 0 affected participants among 1 participant at risk in the Kedbumin 25% arm, and 0 among 2 at risk in the normal saline arm. The registry lists no serious adverse-event terms. These are counts from the small group enrolled; they should not be interpreted as evidence that serious events are absent in either treatment group more broadly. Deaths are not reported in the registry record.
For other adverse events, the registry reports 0 affected participants among 1 at risk in the Kedbumin 25% arm and 1 among 2 at risk in the normal saline arm. These counts describe participants with an event, rather than the total number of event episodes. The record does not provide event descriptions for these other adverse events in the listed results, nor does it explain the collection or coding procedures.
In general, adverse-event counts are easier to interpret when the observation period, event definitions, severity grading, and completeness of follow-up are clear. The registry’s primary safety assessment had a 3-day timeframe, while the adverse-event outcome descriptions refer to events after treatment without a separate timeframe in the posted summary. The registry record does not report further details needed to determine how completely the small cohort was monitored. These results are descriptive and do not support a stable comparison of safety between arms.
13. What the Result Does, and Does Not, Mean
The posted results establish that the registry recorded no primary endpoint events among the 3 participants enrolled: none among the 1 participant in the Kedbumin 25% arm and none among the 2 participants in the normal saline arm. They also record no serious adverse events in either arm and one participant with an other adverse event in the normal saline arm. These are the observed counts in this study, not estimates that can be assumed to describe other patients or settings.
The study does not provide an estimable primary comparison. The zero counts in both arms do not show equivalence, non-inferiority, or equal safety. No margin for such a conclusion, comparative estimate, confidence interval, or p-value is reported. The sample is too limited to characterize uncommon outcomes with useful precision, and the registry’s early termination further constrains interpretation. This is a statement about the information available in the record, not a judgment about either treatment.
The record also does not establish why the trial ended early, whether the planned recruitment process was completed, or whether follow-up and outcome assessment were complete for every participant. The intended population, planned enrollment, and actual enrollment should be kept distinct. The brief summary describes a larger planned pediatric study, while the posted results concern only 3 enrolled participants.
More broadly, a safety endpoint can be clinically detailed yet remain statistically uninformative when few participants are observed. The primary definition uses multiple clinical signs and measurements, but the registry does not explain the participant-level rule used to classify the outcome or report component-level findings. The result therefore supports only a narrow statement about the recorded primary counts. It does not settle the safety comparison or provide a basis for conclusions about the treatments beyond those observations.
14. Why This Trial Matters Statistically
This trial is a useful example of the distinction between a study’s intended design and the information available from its completed record. The registry describes a randomized, controlled, open-label comparison and an intended pediatric population of at least 60 participants. The posted enrollment is 3, and the study is terminated. The difference matters statistically because planned design features cannot compensate for a very small observed dataset.
The example also shows why zero events should not be mistaken for proof of no risk. When few participants are observed, an event may simply not occur in the enrolled group. The primary counts are zero in both arms, but the comparison is not estimable, so the record cannot quantify a treatment contrast. This illustrates the role of precision: a result can be easy to state as a count while remaining highly uncertain as evidence about a broader population.
Finally, the record highlights how reporting details affect interpretation. Randomization is identified, but its implementation is not described; the trial is labeled both randomized and controlled and as a single-group model; and the primary outcome description does not fully specify how its components became a participant-level event. These are not reasons to assume a particular flaw. They are limits on what can be assessed from the registry record. Reading the results carefully means keeping the observed counts, the stated design, and the missing methodological details separate.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation is the very small enrollment: 3 participants, compared with the intended enrollment of at least 60 described in the brief summary. The study was prematurely stopped, but the reason for termination is not reported in the registry record. The posted results therefore have limited capacity to characterize primary safety outcomes or compare the treatment groups.
The primary outcome comparison is not estimable from the binary results. There is no reported comparative estimate, confidence interval, or p-value. The record does not describe the randomization method, allocation concealment, or outcome-assessor masking. Masking is listed as none, but whether outcome assessors were blinded is not reported in the registry record. The design model is listed as single group despite the randomized, controlled description and two named arms; the record does not explain this classification.
The primary endpoint combines several clinical criteria, but the record does not fully state how these criteria were combined to classify participants or how missing measurements were treated. It does not report participant-level completeness, analysis populations, or a statistical analysis plan. The actual number of sites and the reasons for stopping are also not reported in the registry record. These limitations restrict assessment of study conduct and analysis; they do not show that any particular bias or data problem occurred.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Safety Study of Kedbumin 25% Versus Normal Saline in the Treatment of Post-Surgical Hypovolemia in Pediatric Patients — NCT01531803.
- Registry record last updated 2023-11-15; status last verified 2023-10.
- Results first posted 2021-02-18.
- 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.
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19. Record Summary
NCT01531803 is a Phase 4, open-label study of Kedbumin 25% compared with normal saline for post-surgical hypovolemia in pediatric patients. The registry describes randomized, controlled conduct, while the design model is listed as single group. The study is terminated and was prematurely stopped. It began on 2015-02-05, with primary completion on 2015-07-15.
The primary safety endpoint concerns fluid overload, edema, and other complications secondary to fluid resuscitation over 3 days. Enrollment was 3. The registry reports 0 primary endpoint participants among 1 in the Kedbumin 25% arm and 0 among 2 in the normal saline arm; the two-arm binary comparison is not estimable. Serious adverse events affected 0 of 1 and 0 of 2 participants, respectively. Other adverse events affected 0 of 1 in the Kedbumin 25% arm and 1 of 2 in the normal saline arm. No primary or secondary statistical analyses are listed. The reasons for termination and further analysis details are not reported in the registry record.