The Intra-arterial Vasospasm Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Intra-arterial Vasospasm Trial (NCT01996436), a randomized phase 4 study. The primary outcome is Post Infusion Improvement Ratio (PIIR).

2. Clinical Question

3. Trial Design

The Intra-arterial Vasospasm Trial is listed as a Phase 4, randomized, double-masked, parallel-group study. Its condition is cerebral vasospasm, and the registry record lists enrollment of 92. The listed interventions are nicardipine, verapamil, and the combination of nicardipine, verapamil, and nitroglycerin. Arm descriptions identify intra-arterial administration and describe the procedures as pharmacological angioplasty. The brief summary says that the procedures are standard hospital care procedures and that the drugs are FDA approved.

The stated primary objective is to identify an optimal intra-arterial drug treatment regimen for arterial lumen restoration after cerebral vasospasm following aneurysmal subarachnoid hemorrhage. The registry's hypothesis is that combination infusion of multiple vasodilators is more efficacious than single-agent treatment. This is a stated hypothesis, not a reported finding. A secondary objective concerns clinical outcome at 90 days post discharge, with disability or dependence in daily activities assessed by the Modified Rankin Score.

The registry lists the study status as terminated. The recorded start date is 2016-08-29, and the primary completion date is 2024-04-29. These record details describe the study's listed status and dates; they do not explain why the study was terminated or whether the stated enrollment was achieved as planned. The reason for termination and the recruitment history are not reported in the registry record.

Although randomized allocation and double masking are listed, the registry record does not report the randomization method, masking procedures, allocation ratio, or the roles of people who were masked. Detailed inclusion and exclusion criteria, study sites, and treatment assignment procedures are also not reported in the registry record. The available design description therefore establishes the broad trial structure but does not provide enough detail to assess those operational features.

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.

Before assignment: Of 92 enrolled participants, 91 met inclusion criteria and were randomized to treatment.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Includes all participants who received intervention.

6. Primary Endpoint

The registry lists the primary outcome as Post Infusion Improvement Ratio (PIIR), measured over pre pharmacological angioplasty blood vessel diameter - 0 min, post pharmacological angioplasty blood vessel diameter- 10 min after infusion.

The primary endpoint is titled Post Infusion Improvement Ratio (PIIR). The registry describes it as a measure based on blood-vessel diameter before infusion and after pharmacological angioplasty. The stated time points are 0 min before pharmacological angioplasty and 10 min after infusion. In the endpoint description, A is the pre-infusion blood-vessel diameter and B is the post-infusion blood-vessel diameter; PIIR is defined as ((B - A) / A) *100. The endpoint is intended to represent the change in vessel diameter relative to the pre-infusion diameter.

In general, measuring a vessel before and after an intervention can describe an immediate anatomical response. A ratio expresses the change in relation to the starting measurement rather than only as an absolute change. That may be useful when starting diameters vary, although the registry record does not explain the rationale for selecting this endpoint or how diameter was measured.

The endpoint lists its unit as participants and its parameter as a count of participants, while its description defines a ratio based on diameters. This difference in presentation makes it unclear how the endpoint was categorized or summarized in the results. The registry record does not report a primary-outcome result, a comparison between regimens, or details of the analysis used for PIIR. It also does not report the handling of repeated vessel measurements or any threshold used to classify improvement.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is a method for assigning participants to treatment groups by chance. In general, random allocation can reduce systematic differences between groups at the start of a study, especially when allocation is implemented as planned. It does not guarantee that groups will be identical, and it does not remove the need to report baseline characteristics, outcome availability, and the analysis method. The registry labels this study randomized, but the random sequence method, concealment procedures, and allocation ratio are not reported in the registry record.

Double masking generally means that more than one relevant party is kept unaware of treatment assignment. Masking can reduce the chance that expectations influence care, measurement, or assessment. The precise parties masked and the procedures used to maintain masking are not reported in the registry record. Because the primary endpoint is based on vessel diameter, the method of measurement and whether assessors were masked are details that would help readers evaluate potential measurement bias; those details are not reported.

The parallel-group label indicates that the study is described as assigning participants to groups that receive different regimens rather than describing a crossover design. The registry lists nicardipine, verapamil, and the combination regimen. It does not report the allocation ratio or a complete analysis plan, so the intended statistical contrasts cannot be reconstructed from the design labels alone. A randomized design is not by itself evidence that a treatment difference exists.

What does the primary endpoint represent?

PIIR is defined from vessel diameter before infusion and at 10 min after infusion. As a general statistical concept, a change score uses information from measurements at more than one time point. A relative change expresses the change in relation to a starting value, whereas an absolute change is expressed in the original measurement scale. The choice can affect interpretation, particularly when baseline values vary. The registry gives the formula but does not report measurement reliability, the measurement scale, rules for handling multiple vessels, or the analysis model.

The endpoint description presents PIIR as a ratio, but the listed unit is participants and the parameter is a count of participants. These descriptions imply different forms of summary: a continuous ratio and a participant count are not interchangeable. The record does not explain whether a threshold was used to turn a ratio into a count, or whether the outcome was categorized in another way. The endpoint's result structure should therefore not be inferred beyond the definitions actually stated.

Why do uncertainty and dispersion matter?

In general, an estimate from a sample is subject to sampling variation. A confidence interval conveys uncertainty around an estimate, and a standard error is one way of expressing the estimate's sampling variability. The form of interval and model should suit the type of outcome and the design. For a count or binary outcome, the statistical method should account for the outcome's distribution and the number of participants contributing data. For repeated or clustered measurements, methods may also need to account for dependence among observations. These are general considerations; the analysis approach for this trial is not reported in the registry record.

Over-dispersion is a general issue when observed variation in count data exceeds what a chosen statistical model expects. If it is ignored, uncertainty can be understated and statistical tests can be poorly calibrated. This concern cannot be evaluated for the primary endpoint from the registry information because no analysis or outcome distribution is reported. The term is relevant as a general methods consideration, not as a claim that over-dispersion occurred in this trial.

What can planning calculations establish?

Planning calculations use assumptions about an effect, variability, significance level, allocation, and analysis method to illustrate the amount of information a future study might need. The registry record does not report its sample-size justification, assumed effect, or a formal power calculation. Any planning illustration based on the observed effect is not the trial's design justification and is not observed power. Without a posted primary effect estimate, a planning illustration also cannot supply evidence that the treatment effect is real or precisely estimated.

In general, power is a design property: it concerns the chance that a specified analysis would detect a specified effect under stated assumptions. It is not a retrospective measure of whether a completed study succeeded. A sample-size figure generated under a hypothetical effect and allocation is therefore a planning aid, not a result about the participants enrolled in this study. No interim analyses or stopping rules are reported in the registry record.

How should the safety counts be approached?

Counts of participants with events are descriptive summaries. A participant count differs from an event count if a participant can experience more than one event. The registry's event-count meaning describes participants with an event, but the record does not provide further counting rules or definitions for the displayed adverse-event categories. In general, comparisons of event counts require consideration of denominators, follow-up duration, event definitions, and uncertainty. The registry does not report an inferential safety analysis or enough detail to establish those elements fully.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, including the primary PIIR endpoint and the secondary outcome of disability or dependence in daily activities assessed by the Modified Rankin Score. The brief summary places the secondary clinical outcome at 90 days post discharge. The record does not report a statistical analysis plan explaining how these outcomes were ordered, prioritized, or analyzed together. It also does not report adjustments for multiple comparisons, a hierarchy of hypotheses, or a strategy for controlling the chance of false-positive findings across outcomes and treatment contrasts.

Multiplicity matters in general when several outcomes, time points, categories, or pairwise comparisons are examined. The more opportunities there are to identify an apparently notable result, the more important it is to understand whether comparisons were prespecified and how interpretation accounts for them. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. No analyses are listed, so the record does not permit assessment of how those categories or time points were handled.

Missing-data methods are not reported in the registry record. There is no posted accounting of participants with missing PIIR measurements or Modified Rankin Score assessments, reasons for missingness, or methods used to include incomplete records. The final analysis population and any distinction between intention-to-treat and per-protocol analyses are also not reported. These details matter because missing measurements can change which participants contribute to an estimate and can affect how broadly that estimate applies.

The record does not report interim analyses, early stopping criteria, or the reason for termination. It therefore does not establish whether results were reviewed before termination or whether any stopping rule was applied. These are unknowns, not evidence that such procedures were or were not used.

11. 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: poor prognosis leading to death (6.9%), respiratory failure secondary to subarachnoid hemorrhage leading to death (3.4%), elevated intracranial pressure (3.4%), stroke (3.4%), subarachnoid hemorrhage leading to death (3.1%).

The posted safety counts are organized by treatment group. For nicardipine, 32 participants were at risk for serious adverse events and 4 were affected; 32 were at risk for other adverse events and 21 were affected; deaths numbered 2. For verapamil, the corresponding figures are 31 at risk for serious adverse events and 0 affected, 31 at risk for other adverse events and 13 affected, and 0 deaths. For nicardipine + verapamil + nitroglycerin, 29 were at risk for serious adverse events and 5 were affected, 29 were at risk for other adverse events and 27 were affected, and deaths numbered 3.

These are counts, not adjusted comparisons or evidence of causation. A count of affected participants is not necessarily a count of all events, because the registry record does not report whether a participant could contribute multiple events or how events were grouped. The record does not report the safety-analysis method, follow-up duration for these counts, or treatment attribution. Group counts should therefore be read descriptively rather than as a ranking of regimen safety.

The registry also lists serious-event terms with percentages: Poor prognosis leading to death, 6.9%; respiratory failure secondary to Subarachnoid hemorrhage leading to death, 3.4%; Elevated Intracranial Pressure, 3.4%; Stroke, 3.4%; Subarachnoid hemorrhage leading to death, 3.1%; and Intracranial Hemorrhage, 3.1%. The denominator and calculation basis for these term percentages are not reported in the registry record, so they should not be converted into participant counts or compared directly with the group counts.

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

The registry record establishes that a randomized, double-masked, parallel-group study was registered to examine intra-arterial regimens for cerebral vasospasm. It identifies a primary endpoint based on vessel diameter before infusion and 10 min after infusion, and a secondary clinical outcome assessed by the Modified Rankin Score at 90 days post discharge. It also records enrollment of 92 and a terminated status. These registry entries describe the study's stated purpose and record status; they do not establish its findings.

No primary-outcome analysis is reported. As a result, the registry record does not show which regimen produced a larger PIIR, whether any between-group difference was estimated, or how uncertain such an estimate would be. The registry's hypothesis that a combination of vasodilators is more efficacious than single-agent treatment remains a hypothesis in the absence of reported analysis. No conclusion about comparative efficacy can be drawn from the endpoint definition or the stated trial objective alone.

The safety counts describe participants affected in each listed group, along with deaths. They do not by themselves establish that a treatment caused an event, nor do they provide a statistical comparison between regimens. The serious-event terms are accompanied by percentages whose denominator is not reported in the registry record. The counts and percentages therefore need to be understood as posted safety descriptions with limitations in their accompanying detail.

In general, a randomized study can support causal interpretation when allocation, follow-up, outcome measurement, and analysis are adequately reported and conducted. Randomization does not make an incomplete record conclusive. Missing analysis results, missing-data information, and limited detail on implementation leave important uncertainties about precision and potential bias. The registry record also does not explain why the trial was terminated.

The appropriate interpretation is therefore bounded: the record describes the intended comparison, design labels, endpoint, secondary outcome, and safety information, but does not report an efficacy result. It cannot establish that a regimen is superior, equivalent, or ineffective. Nor can it establish that the posted event counts represent a complete or comparative account of harms.

13. Why This Trial Matters Statistically

This trial raises an important statistical distinction between an intended question and an answer supported by results. Its stated objective is to compare intra-arterial drug regimens for arterial lumen restoration after cerebral vasospasm, and its primary endpoint is defined using vessel diameter before and after infusion. Yet the registry record lists no analyses. The endpoint definition and trial hypothesis cannot substitute for an estimated treatment contrast.

The record also illustrates why clear outcome specification matters. PIIR is described as a ratio derived from diameter measurements, while its unit is listed as participants and its parameter as a count of participants. The record notes that the primary outcome has several categories or time points and is not reduced to one comparison. Without analysis details, readers cannot tell how those features were resolved or how the endpoint was summarized.

Randomization and masking are meaningful design features, but their labels alone do not settle questions about implementation, data completeness, or measurement. Information about allocation, masking roles, endpoint assessment, missing data, analysis populations, and prespecified comparisons helps readers evaluate how much confidence to place in a result. Much of that information is not reported in the registry record.

The safety information offers another useful statistical lesson: raw counts can describe what was recorded without establishing comparative risk or causation. Denominators, event definitions, follow-up, and uncertainty all shape interpretation. The listed serious-event percentages have no reported denominator in the record, which limits their use for comparison.

For clinical researchers and biostatisticians, the central point is that design features, outcome definitions, and posted results serve different purposes. A study can have a clear clinical motivation and a randomized design while still lacking the results needed to quantify an effect. Careful interpretation keeps those distinctions visible and treats unreported analyses as unknown rather than filling gaps with assumptions.

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 registry record does not report the primary-outcome results or any analyses. This is the central limitation for interpreting the study's main question: there is no reported estimate of PIIR by treatment group, no treatment contrast, and no precision measure. The record states that the primary outcome has several categories or time points and is not reduced to one comparison, which further limits interpretation of the intended endpoint.

The outcome description has an apparent presentation ambiguity. PIIR is defined as a ratio using pre-infusion and post-infusion vessel diameters, but the endpoint is also listed as a count of participants with unit participants. The record does not explain whether a threshold or category converted the ratio to a participant count. Measurement procedures, assessor masking, and rules for selecting or combining vessel measurements are not reported.

The record does not report eligibility criteria, baseline characteristics, group allocation procedures, or detailed masking methods. It also does not report missing-data handling, analysis populations, treatment adherence, or the statistical plan. These omissions limit assessment of comparability, outcome completeness, and the relevance of any potential analysis. The reason for termination is not reported in the registry record.

Safety reporting also has limits. The record gives group-level counts for serious adverse events, other adverse events, and deaths, but does not report event timing, duration of follow-up for those summaries, attribution, or full counting rules. The denominators for the listed serious-event percentages are not reported. The safety information is consequently descriptive and cannot support a well-specified comparative risk analysis.

Finally, enrollment of 92 and the listed terminated status do not establish how many participants contributed to each outcome or whether all intended follow-up was completed. The registry record does not report a sample-size justification or interim-analysis plan. These absences should be treated as limits on what can be concluded from the record, not as evidence about procedures that may have been used.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Intra-arterial Vasospasm Trial — NCT01996436.
• Registry record last updated 2025-05-11; status last verified 2025-04.
• Results first posted 2025-05-11.
• 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 Intra-arterial Vasospasm Trial (NCT01996436) is listed as a Phase 4 randomized, double-masked, parallel-group study of intra-arterial nicardipine, verapamil, and a combination of nicardipine, verapamil, and nitroglycerin for cerebral vasospasm. Enrollment is listed as 92. The registry records a start date of 2016-08-29, a primary completion date of 2024-04-29, and a terminated status.

The primary endpoint, Post Infusion Improvement Ratio, is defined from vessel diameter before infusion and 10 min after infusion. A secondary outcome is disability or dependence in daily activities assessed by the Modified Rankin Score, with the summary describing clinical outcome at 90 days post discharge. The registry lists safety counts by treatment group and several serious-event terms.

No analyses are listed, and no primary-outcome result or treatment comparison is reported. The reason for termination, sample-size justification, analysis populations, missing-data methods, and multiplicity plan are not reported in the registry record. The posted information describes the trial's intended question and recorded safety counts but does not establish comparative efficacy.