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Aortic Valve Failure Single Group Prospective Investigation NCT03381989

BASILICA: Complete Statistical Analysis of BASILICA in Aortic Valve Failure

An independent statistical review of the BASILICA prospective investigation, evaluating intentional aortic leaflet laceration with an ASHI_INTECC Astato XS 20 0.014 guidewire in participants with native and valve-in-valve aortic valve failure.

Study period: 2018-02-14 to 2018-09-30  ·  Status: Completed  ·  Sponsor: National Heart, Lung, and Blood Institute
Scope of this record

This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.

1. Trial at a Glance

BASILICA was a completed, single-group, open-label prospective investigation in participants with native and valve-in-valve aortic valve failure. The intervention was the ASHI_INTECC Astato XS 20 0.014 guidewire, and the registry lists 31 participants enrolled.

31
Enrollment
Single-group study
1
Study arm
Open-label treatment
1 day
Procedure endpoint
Measured at catheterization-lab exit
30 days
Safety endpoint
MACE freedom
FeatureBASILICA
ClinicalTrials.gov identifierNCT03381989
AcronymBASILICA
TitleBioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction (BASILICA) Prospective Investigation
ConditionNative and Valve in Valve Aortic Valve Failure
StatusCOMPLETED
Study typeSingle-group prospective investigation
AllocationNA
MaskingNONE
Primary purposeTREATMENT
Enrollment31
Number of arms1
Lead sponsorNational Heart, Lung, and Blood Institute (NHLBI)
Sponsor typeNIH

2. Clinical Question

The registry-defined clinical setting is native and valve-in-valve aortic valve failure. The central statistical question is not a randomized treatment comparison; instead, the study evaluates whether the BASILICA procedure can achieve its prespecified procedural objectives and whether participants remain free from major adverse clinical events through 30 days.

Population

Participants with native and valve-in-valve aortic valve failure enrolled in the prospective BASILICA investigation.

Intervention

ASHI_INTECC Astato XS 20 0.014 guidewire (device).

Comparator

There was no comparator arm. The registry describes a single-group study with 1 arm.

Primary questions

How many participants achieve procedure success at exit from the catheterization laboratory, and how many remain free from MACE at 30 days?

3. Trial Design

BASILICA used a SINGLE_GROUP design with no allocation procedure and no masking. Because every participant was assigned to the same intervention arm, the principal statistical task is estimation of observed procedural and safety-event proportions rather than estimation of a between-group treatment effect.

01
Enroll31 participants
02
TreatBASILICA device procedure
03
Exit assessmentProcedure success at 1 day
04
Follow-up30-day MACE assessment
05
SafetySerious adverse events by arm
Design model
SINGLE_GROUP
Allocation
NA
Masking
NONE
Primary purpose
TREATMENT
SINGLE ARM · Enrollment = 31

Open-label treatment

  • ASHI_INTECC Astato XS 20 0.014 guidewire
  • Single-group prospective investigation
  • No masking
  • No comparator arm
SAFETY REPORTING · 13/30

Serious adverse events

  • Single Arm: Open-label Treatment
  • 13 affected participants
  • 30 participants at risk

The difference between the enrollment figure of 31 and the serious-adverse-event denominator of 30 is important when reading the registry record. The safety result is explicitly reported using 30 participants at risk; that denominator should be retained rather than substituted with the overall enrollment count.

4. Primary Endpoints

The registry identifies two primary endpoints. Both are count-based outcomes evaluated within the single treatment group rather than comparisons between randomized groups.

Primary endpointTime frameRegistry definition
Number of Participants With Procedure Success, Measured at Exit From the Catheterization Laboratory 1 day Successful BASILICA traversal and laceration; immediate survival; successful first TAVR device implantation; absence of coronary artery obstruction; and freedom from emergency cardiac surgery or reintervention related to the BASILICA or TAVR procedure.
Number of Participants Were Safety Endpoint is Freedom From Major Adverse Clinical Events (MACE) 30 days Freedom from major adverse clinical events (MACE) according to Valve Academic Research Consortium (VARC-2) at 30days.

Statistically, each primary endpoint can be represented as a binary outcome: participants either satisfy the complete endpoint definition or they do not. That structure is different from a continuous endpoint, where a mean change might be the primary quantity of interest, and different from a time-to-event endpoint, where the timing of an event is central to the analysis.

5. Results

The registry marks results as posted for both primary endpoints. However, no numerical endpoint results, effect estimates, confidence intervals, or p-values are contained in the registry material represented here, and no formal statistical analyses were posted to ClinicalTrials.gov.

Procedure Success

Primary endpoint · 1 day

Results posted: Yes

Endpoint: Number of Participants With Procedure Success, Measured at Exit From the Catheterization Laboratory

The registry defines success using the combined criteria of BASILICA traversal and laceration, immediate survival, successful first TAVR device implantation, absence of coronary artery obstruction, and freedom from emergency cardiac surgery or reintervention related to BASILICA or TAVR.

Clinical Biostats interpretation

This is a composite binary procedural endpoint. A participant must satisfy all elements of the registry definition to count as a procedure success. Therefore, the endpoint is more demanding than simply documenting successful device use or successful leaflet laceration.

The clinically meaningful statistical quantity would normally be the observed proportion of participants meeting the complete success definition, accompanied by a confidence interval. Because the registry does not report the numerical endpoint result here, there is no reported proportion or confidence interval to interpret.

A confidence interval, when available for a single-group proportion, describes uncertainty around the estimated population proportion; it does not describe the range of outcomes that an individual participant might experience. A p-value, if one had been prespecified against a benchmark, would address evidence against that benchmark under the stated testing framework; it would not measure the magnitude of procedural success.

Freedom From Major Adverse Clinical Events

Primary safety endpoint · 30 days

Results posted: Yes

Endpoint: Number of Participants Were Safety Endpoint is Freedom From Major Adverse Clinical Events (MACE)

Registry definition: freedom from major adverse clinical events according to Valve Academic Research Consortium (VARC-2) at 30 days.

Clinical Biostats interpretation

This endpoint is also a binary proportion, but its interpretation is safety-focused. The relevant outcome is whether a participant remains free from the registry-defined MACE endpoint at the specified 30-day assessment.

The registry does not report the numerical count for this primary endpoint in the material represented here. Consequently, a success proportion, confidence interval, or formal hypothesis-test result is not available for interpretation.

The distinction between the procedure endpoint and the 30-day MACE endpoint is statistically important. Procedure success is assessed at the catheterization-laboratory exit with a 1-day time frame, whereas MACE freedom evaluates a later 30-day clinical status. They therefore capture different stages of the treatment pathway.

6. Safety Results

The registry reports serious adverse events by treatment arm as 13/30 for the single open-label treatment arm. The denominator is the number of participants at risk specified by the registry for this safety measure.

Safety measureSingle Arm: Open-label Treatment
Participants affected by serious adverse events13
Participants at risk30
Reported format13/30

Because this is a single-arm study, the safety result describes the observed frequency within the treated cohort. It does not estimate an excess risk relative to an untreated or alternative-treatment population. Without a comparator group, a causal attribution of the observed serious-adverse-event frequency to the device cannot be obtained from a between-group randomized comparison.

Safety denominator matters: the registry reports 13 affected participants among 30 participants at risk. The enrollment count is 31, so the safety denominator should not automatically be replaced by the overall enrollment figure.

7. Statistical Methodology

Single-group proportion estimation

Both primary endpoints have a binary structure: procedure success versus no procedure success, and freedom from MACE versus MACE. In a single-group design, the natural descriptive statistic is the observed proportion meeting the endpoint.

Conceptual form
p̂ = x / n

where x is the number of participants meeting the endpoint and n is the corresponding number evaluated for that endpoint.

For a study of this size, an exact binomial confidence interval would generally be preferable to relying on a large-sample normal approximation when the observed number of events or successes is small. The exact method remains defined by the binomial sampling model and does not require the estimated proportion to be comfortably away from 0 or 1.

Why a single-arm study does not produce a treatment hazard ratio

A hazard ratio is fundamentally a comparative measure: it describes the relative instantaneous event rate between two groups under a specified survival model. BASILICA has one treatment arm, so there is no randomized control hazard against which a treatment hazard can be compared.

Comparative versus single-group analysis
Two-arm trial → treatment effect comparison   |   Single-arm trial → observed proportion / outcome distribution

The statistical question changes when there is no comparator. Estimation focuses on what was observed in the treated cohort rather than on a randomized contrast.

Composite endpoint structure

Procedure success is defined using multiple required components. Composite endpoints can increase clinical specificity by requiring a collection of conditions to be satisfied, but they also make interpretation dependent on every component of the definition. Failure of any required component prevents the participant from being counted as a procedure success.

Safety analysis

The registry reports serious adverse events using an affected-versus-at-risk format. This is an appropriate descriptive representation for a single-arm safety assessment because it makes both the numerator and denominator explicit.

Time frames and analysis sets

The primary endpoints have fixed assessment windows of 1 day and 30 days. The statistical denominator should correspond to the participants eligible for or evaluated at the relevant assessment rather than automatically using the overall enrollment count.

8. Statistical Methods Explained

Why are the primary endpoints analyzed as proportions?

Each primary endpoint has a yes-or-no outcome. Procedure success is defined by a complete set of procedural and immediate clinical conditions, while the safety endpoint asks whether participants are free from MACE at 30 days. For this structure, the basic estimand is the proportion of participants meeting the endpoint.

Why is there no treatment-effect hazard ratio?

A hazard ratio requires a comparison between groups or another explicitly defined reference hazard. BASILICA is a single-group study, so the registry does not provide a randomized comparator. An observed proportion is therefore the more direct summary of a binary endpoint.

Why does the 1-day procedure endpoint differ from the 30-day safety endpoint?

The endpoints answer different clinical questions. The 1-day endpoint focuses on immediate procedural success at exit from the catheterization laboratory. The 30-day endpoint evaluates freedom from MACE according to VARC-2 over a longer follow-up period.

Why does a composite procedural endpoint require careful interpretation?

A composite definition can capture several clinically important requirements simultaneously. But the resulting success proportion represents participants satisfying the entire definition, not merely participants achieving one favorable component. This makes the exact endpoint wording essential when interpreting the numerator.

What would a confidence interval add?

A confidence interval around a single-group proportion would quantify statistical uncertainty around the observed estimate. With a relatively small cohort, the interval can be materially wider than the point estimate suggests. The width reflects information available for estimation; it is not a statement about individual patient variability.

Why should the safety denominator be preserved?

The registry explicitly reports serious adverse events as 13/30. Using 31 as the denominator would answer a different question from the one represented by the registry's stated at-risk population. In clinical-trial statistics, denominator definition is part of the endpoint itself.

9. Planned Analysis and Interpretation Framework

The registry reports both primary endpoints as having results posted, but numerical statistical estimates are not reported in the material represented here. For endpoints of this type, the usual statistical presentation would begin with the number of participants meeting the endpoint and the number evaluated, followed by the corresponding observed proportion and an appropriate confidence interval.

Endpoint typeTypical statistical summaryKey interpretation
Procedure successCount and proportion of participants satisfying the complete success definition; confidence interval for the single-group proportionDescribes the observed frequency of complete procedural success
30-day MACE freedomCount and proportion free from MACE; confidence interval for the single-group proportionDescribes the observed 30-day safety outcome
Serious adverse eventsAffected participants / participants at riskDescribes observed serious-adverse-event frequency in the treatment cohort

No comparative treatment-effect estimate is appropriate without a comparator group. Similarly, a p-value would require a prespecified null hypothesis or benchmark. A single-arm descriptive estimate and its confidence interval answer an estimation question rather than a randomized comparative question.

10. Understanding the 13/30 Safety Result

Statistical interpretation

The registry reports 13/30 participants affected by serious adverse events among the participants at risk in the single open-label treatment arm. The numerator identifies the number affected and the denominator identifies the population at risk used for that safety measure.

This result is a descriptive frequency within the study cohort. It is not a relative risk, odds ratio, hazard ratio, or risk difference because there is no comparator arm.

What the result does not establish

The 13/30 figure does not by itself establish how the serious-adverse-event frequency compares with another treatment, historical population, or untreated group. Such comparisons require an appropriate reference population and a prespecified analysis framework.

Why the denominator matters

The registry distinguishes overall enrollment of 31 from the 30 participants at risk used for this safety result. That distinction should remain visible whenever the safety outcome is summarized.

11. Clinical Interpretation vs Statistical Interpretation

Statistical interpretation

BASILICA provides a single-group framework in which procedural success and 30-day MACE freedom are binary endpoints. The registry identifies both primary endpoints as having results posted, but numerical estimates and formal statistical analyses are not reported in the material represented here.

Clinical interpretation

The study was designed around procedural performance and short-term clinical safety in participants with native and valve-in-valve aortic valve failure. Its endpoints therefore describe the feasibility and immediate clinical pathway of the intervention rather than a randomized comparison of treatment strategies.

12. Limitations and Interpretation Issues

13. Why This Trial Matters Statistically

BASILICA is a useful teaching case because it illustrates an important branch of clinical-trial statistics that is different from the familiar randomized phase 3 framework. The central analytical problem is estimation within a single treated cohort, with procedural and safety outcomes defined at specific follow-up times.

ConceptHow it appears in BASILICA
Single-group designOne treatment arm with no comparator
Binary endpointProcedure success and freedom from MACE are expressed as participant-level yes/no outcomes
Composite endpointProcedure success requires successful traversal and laceration, immediate survival, successful first TAVR device implantation, absence of coronary obstruction, and freedom from emergency surgery or reintervention
Fixed assessment timeProcedure success is assessed at 1 day and MACE freedom at 30 days
Proportion estimationSingle-arm binary outcomes are naturally summarized using observed counts and proportions
Confidence intervalsUseful for expressing uncertainty around single-group proportions, particularly in small samples
Safety denominatorSerious adverse events are reported as 13/30, with 30 explicitly identified as the at-risk denominator
No randomized treatment effectWithout a comparator, relative measures such as risk ratios and hazard ratios are not treatment effects estimated from randomization

14. Trial Timeline

2018-02-14

Study start

The registry lists 2018-02-14 as the study start date.

2018-09-30

Primary completion

The registry lists 2018-09-30 as the primary completion date.

Completed

Registry status

The study status is recorded as COMPLETED, with enrollment of 31 participants and 1 study arm.

15. Endpoint-by-Endpoint Statistical Reading

QuestionProcedure success30-day MACE freedom
What is measured?Whether the complete BASILICA procedural-success definition is satisfiedWhether the participant remains free from MACE according to VARC-2
Time frame1 day30 days
Endpoint typeBinary composite outcomeBinary safety outcome
Study structureSingle treatment groupSingle treatment group
Natural summarySuccess count / evaluable participantsMACE-free count / evaluable participants
Comparative effect?No randomized comparatorNo randomized comparator

This distinction also clarifies why the registry endpoints should not be treated like conventional overall-survival or progression-free-survival outcomes. There is no time-to-event modeling requirement inherent in the endpoint definitions as stated. Instead, the registry specifies categorical outcomes assessed at defined clinical time points.

16. What a Formal Statistical Report Would Add

A complete formal statistical presentation of the two primary endpoints would normally identify the endpoint numerator and denominator, calculate the observed proportion, provide a confidence interval using a prespecified method, and state any hypothesis-testing benchmark if one had been specified in the statistical analysis plan.

For the serious-adverse-event result, the registry already supplies the affected count and at-risk denominator as 13/30. For the primary efficacy and safety endpoints, the registry material represented here supplies the endpoint definitions and indicates that results are posted, but it does not provide the numerical estimates needed for a quantitative effect summary.

Interpretation principle: in a single-arm investigation, precision and endpoint definition are central. A proportion without its denominator is incomplete, while a treatment-effect measure without a comparator is not a randomized treatment effect.

17. Sources

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18. Record Summary

BASILICA is a completed single-group prospective investigation of an ASHI_INTECC Astato XS 20 0.014 guidewire intervention in native and valve-in-valve aortic valve failure. Its two primary endpoints focus on procedure success at 1 day and freedom from MACE at 30 days. Statistically, the study is best understood as a single-arm estimation problem rather than a randomized comparative trial: the key quantities are endpoint-specific counts and proportions, together with appropriate measures of uncertainty.

The registry reports enrollment of 31 participants and identifies 1 treatment arm. For serious adverse events, the reported result is 13 affected participants among 30 participants at risk. The registry marks the primary endpoints as having results posted, but numerical endpoint estimates, confidence intervals, and p-values are not reported in the material represented here. That distinction is important because statistical interpretation depends not only on the endpoint definition but also on the denominator, analysis population, and study design.

Clinical Biostats methodology: The statistical story of a clinical investigation depends on its design. For BASILICA, the central concepts are single-arm estimation, binary and composite endpoints, endpoint-specific denominators, fixed clinical assessment windows, and careful separation of descriptive safety frequencies from comparative treatment effects.