Fattori di Rischio ed Outcome Dell'Ictus Ischemico da Occlusione Tandem di Circolo Anteriore e Posteriore

CERES-TANDEM is a multicenter study designed to improve the understanding of "tandem" ischemic stroke -those caused by two blockages in series, one in a neck artery and one in a brain artery-. Because tandem occlusion-related stroke tend to cause more severe brain injury and have been under-represented in major clinical trials, there is no clear consensus on which treatments work best. This study will help identify who is most at risk and which therapies lead to the best recovery.

OBJECTIVES:

Identify Risk Factors: Compare common stroke risk factors (e.g., high blood pressure, diabetes, high cholesterol, smoking) in patients with tandem occlusion versus those with single-site large vessel occlusions.

Compare Clinical Outcomes of Reperfusion: Evaluate whether acute reperfusion treatments-such as clot-dissolving drugs (thrombolysis), mechanical clot removal (thrombectomy), and emergent carotid stenting-lead to better 3-month functional outcome (assessed by the modified Rankin Scale, ranging 0 to 6, with good functional outcome identified with mRS score 0-2) compared to medical management alone in tandem occlusion and isolated cervical artery occlusion.

Assess Post Stent Therapy: Among patients who receive emergent stenting, determine whether different post-stenting regimens (antiplatelet agents, anticoagulants, or no additional therapy) affect functional outcomes, bleeding events, or stroke recurrence.

STUDY DESIGN:

Type: cohort study pooling data from prospective registries of cerebrovascular diseases at participating sites Setting: Stroke Unit, Cesena Hospital (PI MR), Interventional Neuroradiology, Vall d'Hebron Research Institute, Barcelona (PI FD), Radiology, Boston Medical Center (PI TN); and other participating stroke centers Time Frame: Patients treated between 2018 and 2024. Sample Size: Approximately 2800 cases overall

DATA COLLECTION:

Sources: Clinical records, imaging reports (CT perfusion, angiograms), lab results, hospital discharge summaries, and longitudinale stroke registry databases.

Data Safety: case information is anonymized using encrypted study IDs; only aggregate data will be reported.

Follow-Up: Standard-of-care follow-up visits at 3 months (minimum) and up to 12 months or until death. Outcomes include functional status (mRS), recurrence of stroke or TIA, symptomatic intracranial hemorrhage, major bleeding, and all-cause mortality

OUTCOMES AND ANALYSIS:

Primary Outcome: Functional outcome, identified by the mRS and tested between groups with ordinal shift between mRS categories (0-6).

Secondary Outcomes: functional status at 3 months (excellent outcome mRS 0-1, good outcome mRS 0-2) Additional outcomes: early neurological deterioration; symptomatic intracerebral hemorrhage and successful recanalization (defined as TICI 2b or higher).

PLANNED ANALYSIS (see Detailed Description for full analytical protocol):

• Compare outcomes in emergent stenting vs no stenting groups depending on stent subtype and endovascular approach
• Compare outcomes in emergent stenting vs no stenting groups depending on antithrombotic treatment before, during and after the endovascular procedure
• Define the potential impact of early statin treatment on the interplay between stenting vs no stenting and the outcomes.

STATISTICS:

Medians with IQRs and means with SDs together with percentages will be used to present the distribution of ordinal, continuous, and categorical variables. Baseline characteristics across groups will be compared using the Pearson χ2 test for categorical variables and t test or the Kruskal-Wallis test, as appropriate, for continuous and ordinal variables.

Given the nature of data deriving from prospective registries, inverse probability of treatment weighting (IPTW) will be implemented, which is an application of propensity scores that calculates the probability of being exposed to one treatment versus the other and creates a pseudo-population based on the probabilities so that potential confounders are equally distributed across the treatment groups.

Models will be weighted for prespecified variables known to potentially impact the outcome, and will also consider factors of imbalance between groups. In case of crossovers, a stratum-based analysis according to predefined estimand will be applied (direct intervention effect on outcomes and total-effect; estimand approach in detailed description).

DISSEMINATION The results will be disseminated in international peer reviewed journals.

CERES-TANDEM is promoted by

• Bufalini Stroke Center, AUSL Romagna, Cesena, Italy (PI Dr. M. Romoli)
• Interventional Neuroradiology Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain (PI Dr. F. Diana)
• Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA (PI Dr. T. Nguyen)