Seeking clarification on the operational definition of the primary endpoint in the TRACE trial: a perspective from Chinese neurointerventional practice

We read with great interest the published study protocol for the TransRadial versus transfemoral Access for CErebral angiography (TRACE) trial in the Journal of Neurointervention (1). As neurointerventionalists practicing in China, we commend the investigators for this pivotal multicenter, randomized trial. Its outcomes are eagerly anticipated and hold the potential to significantly influence clinical practice, particularly in our region where the adoption of transradial access (TRA) is accelerating.

Our clinical experience, however, highlights a pertinent reality in many Chinese centers: routine TRA cerebral angiography often aims for selective catheterization of the proximal great vessels (e.g., subclavian and common carotid arteries), with successful superselective cannulation of distal vessels [e.g., the internal carotid artery (ICA) or vertebral artery (VA)] being less consistently achieved compared to the standard transfemoral access (TFA) approach. This context makes the precise operational definition of the primary endpoint in TRACE—“the rate of successful diagnostic cerebral angiography”—of paramount importance for its interpretation and applicability.

The protocol defines the primary endpoint as “the successful superselection of the aortic arch vessel without changing the arterial approach, with angiography results meeting diagnostic requirements” (1,2). We have identified two key areas where clarification would be invaluable.

First, there is an inherent ambiguity in the term “superselection of the aortic arch vessel”. Anatomically, this could be interpreted as successful catheterization of the first-order branches (e.g., the left common carotid artery). However, the “Intervention” section specifies that the procedure includes superselective angiography of “bilateral internal carotid arteries, common carotid arteries, and vertebral arteries” (1). Is successful catheterization and contrast injection at the level of the ICA and VA, therefore, a mandatory criterion for the primary endpoint adjudicated by the blinded core laboratory? The technical success rate for TRA can differ substantially depending on whether the benchmark is selective common carotid artery angiography versus the more technically demanding selective ICA/VA angiography, especially when navigating from the right radial artery to the left-sided vessels. Clarifying this operational definition is critical for a valid non-inferiority comparison.

Second, the phrase “meeting diagnostic requirements” would benefit from elaboration regarding the completeness of the angiographic series. A truly successful diagnostic angiogram is defined not just by the quality of a single view but by its comprehensiveness in evaluating the neurovascular system. For instance, diagnosing a cavernous sinus dural arteriovenous fistula necessitates a complete six-vessel angiogram (including bilateral ICAs, external carotid arteries, and VAs) to fully assess hemodynamics and identify potential dangerous anastomoses. Was a standardized minimal angiographic series predefined as part of the “diagnostic requirements” for endpoint adjudication?

Providing clarity on these specific operational criteria would greatly strengthen the trial’s validity and ensure its findings are translated appropriately into clinical practice. We respectfully request the authors’ elaboration on the core laboratory’s specific checklist for adjudicating the primary endpoint. We thank the investigators for their valuable contribution and look forward to the trial’s results.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://jni.amegroups.com/article/view/10.21037/jni-26-0006/coif). The author has no conflicts of interest to declare.

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References

1. Yang H, Su J, Gao X, et al. TransRadial versus transfemoral Access for CErebral angiography (TRACE): study protocol for a multicenter randomized trial. J Neurointerv 2025;1:6.
2. ClinicalTrials.gov. Transradial Versus Transfemoral Access for Cerebral Angiography. Identifier: NCT05401669. Available online: https://clinicaltrials.gov/ct2/show/NCT05401669