Albumin for Intracerebral Hemorrhage Intervention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Albumin for Intracerebral Hemorrhage Intervention (NCT00990509), a randomized phase 2 study. The primary outcome is Mean Hyperintense Acute injuRy Marker (HARM).

2. Clinical Question

The clinical question is therefore identifiable from the registered endpoint and comparison, but the posted results do not permit a direct estimate of the difference between albumin and placebo on mean HARM. The record reports that 11 of 14 participants received a Day 5 MRI and that HARM readings could be performed for only 4 of the 7 placebo participants, because of insufficient sequences or the presence of subarachnoid blood. The arm results list no Albumin endpoint value and no estimable comparison. These gaps limit what can be concluded from the posted endpoint data.

3. Trial Design

The study is listed as a randomized, quadruple-masked, parallel-group Phase 2 trial sponsored by Georgetown University. Its condition is intracerebral hemorrhage. The registry lists enrollment of 14 and status as terminated. The start is recorded as 2009-09, with primary completion recorded as 2013-06. The registry record does not explain why the study was terminated or describe the timing and circumstances of that decision.

The planned comparison was albumin versus placebo. The study summary describes three daily injections after enrollment, followed by monitoring and assessments through Day 90. It describes continuous monitoring in the Georgetown ICU through 96 hours after enrollment, with daily blood tests and clinical evaluations through post-enrollment Day 5, as well as daily chest x-rays and EKGs. It also describes clinical evaluations at Day 30 and Day 90. These are descriptions of the study plan; they do not establish which procedures were completed by each participant.

The record lists brain MRI with and without contrast as a procedure, and the primary endpoint is mean HARM at the Day 5 MRI. Although the trial is identified as parallel-group and randomized, the registry record does not report the allocation ratio, the detailed randomization method, or the masking roles. The arm descriptions are blank. It also does not report a sample-size justification or a detailed statistical analysis plan. The small enrollment and incomplete endpoint availability are important context for interpreting the posted results, but the record does not establish why enrollment was limited or why endpoint readings were unavailable.

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.

6. Primary Endpoint

The registry lists the primary outcome as Mean Hyperintense Acute injuRy Marker (HARM), measured over Day 5 MRI.

The primary endpoint is mean Hyperintense Acute injuRy Marker (HARM), measured at the Day 5 MRI and reported in points. The registry describes HARM as characterizing the frequency and severity of blood-brain barrier disruption. It states that the post-contrast study uses a previously developed 5 point scale (0 to 5), where a score of 0 indicates no HARM and a score of 5 indicates diffuse and generalized HARM.

An imaging endpoint can describe a biological or structural feature relevant to a study question. General statistical context: a mean summarizes the average score in a group, while the spread of individual scores indicates how much participants differ from that average. Comparing group means can be informative when scores are available for enough participants and the measurement is sufficiently consistent. The endpoint description does not give a mean or spread for either arm, so the registry record does not permit those features to be assessed.

Availability is particularly important for this endpoint. The record states that 11 of 14 participants received a Day 5 MRI, but that HARM readings could only be performed on 4 of the 7 placebo participants because of insufficient sequences or the presence of subarachnoid blood. It does not provide an Albumin mean, and the posted arm results do not give an estimable two-arm comparison. Consequently, the registry record does not show how HARM scores were distributed or whether the observed scores differed between arms. The measure is registered as primary, but its results are not numerically reported in an interpretable arm-to-arm form.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group comparison with quadruple masking. Randomization is intended, in general, to make treatment assignment independent of participants’ characteristics at assignment. This helps support a fair comparison, particularly when the allocation process is implemented as planned. It does not guarantee that the groups will be alike in every characteristic in a small trial, and it cannot by itself address outcomes that were not measured or reported. The registry record does not describe the randomization procedure, allocation ratio, or which roles were masked.

What would a mean comparison show?

The primary endpoint is a mean HARM score at the Day 5 MRI. General statistical context: a mean is a measure of the center of a set of numerical observations. A comparison of group means would describe the difference in average scores among the participants with usable readings, if group results and an appropriate analysis were reported. The mean alone does not convey how widely scores vary. A measure of spread, such as a standard deviation, can describe variation among individual observations; the registry results do not report one for this endpoint.

A confidence interval is a way to express uncertainty around an estimated quantity. In general, a narrower interval indicates greater precision, while a wider interval indicates greater uncertainty under the analysis assumptions. The registry record gives no confidence interval for mean HARM or for a between-arm contrast. It therefore does not quantify the precision of a treatment comparison. A p-value, if reported, would address compatibility of data with a specified statistical model and null hypothesis; it would not measure the size or clinical importance of an effect. No p-value for the primary endpoint is reported.

Why does endpoint availability matter?

For a group mean to describe the intended study population, it matters which participants have observed scores and which do not. General statistical context: complete-case summaries use only participants with usable measurements. If missingness is related to participant condition, imaging quality, or the outcome itself, the observed participants may differ from those without readings. The direction and size of any resulting bias cannot be inferred without additional information and assumptions. The record identifies insufficient sequences or subarachnoid blood as reasons HARM reads could not be performed for some placebo participants, but it does not report a missing-data analysis or provide enough information to determine how missing readings relate to the underlying HARM scores.

The endpoint account reports 11 of 14 Day 5 MRI scans, while noting that only 4 of 7 placebo participants had readings that could be performed. The posted arm results list no Albumin mean and no estimable two-arm comparison. These registry entries mean that the available record does not support reconstruction of a mean difference or its uncertainty. Reconstructing an analysis would require outcome summaries and assumptions that are not reported in the registry record.

What can be inferred from the trial design?

The randomized design establishes the intended basis for comparing Albumin and Placebo, but the registry does not give the allocation ratio, detailed treatment assignment procedure, or analysis population. An intention-to-treat analysis generally compares participants according to their randomized assignment, regardless of treatment received, while other analysis populations may use different inclusion criteria. These approaches answer related but distinct questions. The registry record does not report which population was used for the endpoint analysis, and the available results do not permit identification of an analysis population.

Quadruple masking indicates a masking designation in the registry, but the record does not specify which study roles were masked or how masking was maintained. Masking is generally used to limit the influence of knowledge of assignment on care, measurement, or interpretation. It does not prevent missing data, and it cannot substitute for transparent reporting of outcomes and analyses.

What does the planning information mean?

General statistical context: a sample-size calculation is a planning tool based on assumptions about the effect to detect, outcome variability, significance level, power, allocation, and analysis. It is not a result observed in the trial and is not “observed power.” The registry description of the planning illustration specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a stated fraction of an observed effect. Such calculations depend on having an observed effect estimate and other required inputs. The posted primary endpoint does not include an estimable arm comparison, so it does not support an interpretation of the observed effect for this endpoint. The registry record does not report the trial’s own sample-size justification.

Over-dispersion is a general concern when count data vary more than a chosen model expects; ignoring it can make uncertainty estimates too small. That concept is not a reported feature of the HARM endpoint, which is described as a score, and the registry record does not report a model for it. More broadly, no endpoint analysis method, variance assumption, adjustment method, or hypothesis-testing plan is reported. As a result, there is no basis in the registry record for describing a particular inferential procedure as the trial’s prespecified method.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and no posted analyses. It identifies mean HARM at the Day 5 MRI as the primary endpoint, but does not report numerical arm results or a comparison. It lists no secondary posted results. The record does not describe whether statistical testing was planned for multiple outcomes, whether any outcome hierarchy or multiplicity adjustment was used, or whether an interim analysis was planned. Those details are not reported in the registry record.

General statistical context: multiplicity arises when several outcomes, time points, or comparisons are tested. Repeated testing can increase the chance of a result that appears unusual under a null model, so a prespecified strategy may be used to control that risk. The number of registered outcome measures alone does not establish how many formal statistical tests were carried out. Since no analyses are posted, it is not possible to determine how multiplicity was handled.

Missing endpoint data are a separate concern. The record reports Day 5 MRI completion for 11 of 14 participants and says HARM readings could only be performed on 4 of 7 placebo participants for the stated imaging reasons. It does not report an imputation method, sensitivity analysis, or analysis population for the primary endpoint. General statistical context: imputation and sensitivity analyses can examine how conclusions depend on assumptions about missing observations, but they cannot recover unobserved outcomes without assumptions. No such approach is described in the registry record.

The record does not report whether all randomized participants were included in the primary analysis, nor does it report treatment receipt by arm. It also does not report a protocol-deviation analysis or an explanation of missing Albumin endpoint results. These omissions prevent assessment of how participants entered the primary endpoint analysis and whether the analysis followed a prespecified plan.

11. 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

Serious events with the highest arm-level rate: pulmonary edema (40.0%), death (22.2%), neurologic deterioration (20.0%).

The registry reports serious adverse events affecting 4 of 5 participants at risk in the Albumin group and 2 of 9 participants at risk in the Placebo group. These counts describe participants reported as affected among those listed at risk; they are not a randomized comparison adjusted for other factors. The record gives no statistical comparison or uncertainty interval for these figures, so the counts should be read descriptively.

The listed top serious adverse event terms are Pulmonary Edema at 40.0%, Death at 22.2%, and Neurologic Deterioration at 20.0%. The registry does not specify in this listing which arm each term belongs to or provide enough context to interpret these percentages as arm-specific risks. Death appears as a listed serious adverse event term, but group-specific death counts are not reported in the registry record.

The adverse event figures do not establish causation. They do not by themselves show whether events were related to albumin, placebo, the underlying condition, or other circumstances. The record also lists no other adverse events in the at-risk groups. Given the limited enrollment and the absence of a reported comparative safety analysis, these data describe what was recorded but do not quantify a precise difference between groups.

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

The posted results establish that this was a randomized Phase 2 study of albumin versus placebo in intracerebral hemorrhage, with enrollment of 14 and a primary endpoint of mean HARM at the Day 5 MRI. They also establish that the endpoint was not available for a complete set of participants: 11 of 14 received an MRI, and HARM readings could only be performed for 4 of 7 placebo participants for the stated imaging reasons. The registry results do not report an estimable mean for either arm or a numerical between-arm comparison.

Accordingly, the registry record cannot show the direction, magnitude, or precision of an albumin-placebo difference in mean HARM. It does not report a confidence interval or hypothesis-test result for the primary endpoint. The absence of an estimable result is not evidence that the groups had the same scores, nor does it establish that one group had higher scores. The relevant numerical comparison is simply not reported in an interpretable form.

The serious adverse event counts provide descriptive safety information, but they are not a formal comparison and do not establish that any event was caused by a treatment. The listed serious event terms are not accompanied by clear arm-specific percentages, and group-specific death counts are not reported. These limitations are distinct from the missing primary endpoint results.

General statistical context: a trial’s design and its results answer different questions. Randomization describes how participants were intended to be assigned; an analysis of observed outcomes is needed to estimate a group contrast. Incomplete measurement and absent analysis details can limit that estimate even when a randomized design was intended. The registry record does not report the trial’s sample-size justification, analysis plan, missing-data method, or reason for termination. Those gaps prevent a fuller assessment of how the study was intended to address its clinical question.

13. Why This Trial Matters Statistically

This trial illustrates the difference between registering a primary outcome and reporting an estimable result for that outcome. Mean HARM at the Day 5 MRI is clearly identified as the primary endpoint, and its measurement is described. Yet the registry results provide no mean by arm and no comparison. Without those values, readers cannot evaluate the size or precision of the primary result, regardless of the randomized design.

Endpoint availability also matters for the interpretation of small trials. The record reports 11 Day 5 MRI scans among 14 enrolled participants, with HARM reads possible for only 4 of 7 placebo participants for the stated imaging reasons. When outcome availability is incomplete, the observed subset may not fully represent the participants who entered the study. A transparent account of which readings were available, why others were missing, and how missingness was handled is important to assess the reliability of an endpoint comparison.

The safety listings demonstrate another statistical distinction: counts and event terms are descriptive evidence, not necessarily a comparative analysis. Counts among small groups can be unstable, and this record does not provide uncertainty estimates or an adjusted safety comparison. The listed percentages also lack clear arm attribution in the record.

More generally, the record does not report the trial’s own sample-size rationale or detailed analysis plan. A planning calculation and a trial’s observed evidence serve different purposes: planning assumptions do not replace reported outcomes, while a completed analysis needs to show both the estimate and its uncertainty. This record makes the design and some safety information visible, but leaves the primary treatment contrast unquantified.

14. 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 central limitation is that the registry record does not report an estimable primary endpoint result. No mean HARM value is listed for Albumin or Placebo, and no between-arm estimate or uncertainty measure is reported. The trial’s primary question therefore cannot be answered quantitatively from the posted results.

Endpoint availability was incomplete. The record states that 11 of 14 participants received a Day 5 MRI, and that only 4 of 7 placebo participants had HARM readings that could be performed because of insufficient sequences or the presence of subarachnoid blood. The record does not give a corresponding reason for the missing Albumin endpoint value, nor does it describe a missing-data strategy or sensitivity analysis. The potential effect of this incomplete measurement on the comparison cannot be assessed.

The registry identifies the trial as randomized and quadruple-masked, but does not report the allocation ratio, detailed randomization method, or which roles were masked. The arm descriptions are blank, and the record does not identify the analysis population or state whether analyses followed randomized assignment. It reports no posted analyses and no secondary outcome results.

Safety information is also limited. Group-specific counts of deaths are not reported, and the top serious adverse event terms are not clearly attributed by arm in the listing. No comparative analysis or uncertainty estimates are provided. The record lists the study as terminated but does not report the reason. It also does not report the trial’s sample-size justification, interim analyses, or detailed statistical plan. These are limitations of the available registry record and do not establish what may have been assessed outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Albumin for Intracerebral Hemorrhage Intervention — NCT00990509.
• Registry record last updated 2014-08-29; status last verified 2014-08.
• Results first posted 2014-08-29.
• 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.

18. Record Summary

The registry record describes a randomized, quadruple-masked, parallel-group Phase 2 study sponsored by Georgetown University, comparing albumin with placebo for intracerebral hemorrhage. Enrollment was 14. The study is listed as terminated, with start recorded as 2009-09 and primary completion as 2013-06.

The primary endpoint was mean HARM at the Day 5 MRI. The record reports incomplete MRI and HARM-reading availability and gives no estimable arm values or primary comparison. It lists serious adverse events affecting 4 of 5 participants at risk in the Albumin group and 2 of 9 at risk in the Placebo group, but does not report a formal comparative safety analysis or group-specific death counts. No analyses are posted. The registry record does not report the reason for termination, the trial’s own sample-size justification, or a detailed statistical analysis plan.