Risk Factors and Outcomes of Ischemic Stroke Associated With Tandem or Isolated Cervical Artery Occlusion in Anterior and Posterior Circulation

NCT06965036 | Active Not Recruiting DMC

• 1 other identifier: 0001765/2024
• Study Type: observational
• Target: 2,880
• Locations: 3 countries
• Sites: 3

Brief Summary

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)

Conditions

Acute Ischemic Stroke Related to Tandem Occlusion; Acute Ischemic Stroke Due to Isolated Cervical Artery Occlusion

Keywords

stroke; tandem occlusion; cervical artery occlusion

Outcome Measures

Primary Outcomes (1)

• modified Rankin Scale

  modified Rankin Scale ranges 0 to 6, with 0 being optimal outcome (full autonomy) and 6 being mortality.

  3 months

Secondary Outcomes (6)

• symptomatic ICH

  within the first 24 hours and within the first 7 days after stroke

• Any PH1-2

  within 7 days after intervention

• Early neurological deterioration

  48 hours

• mortality

  3 months

• Complications

  7 days

Study Arms (2)

emergent carotid (or cervical artery) stenting

An aggressive approach characterized by stenting the extracranial occluded vessel (independently from the retrograde or anterograde approach) during the process of mechanical thrombectomy (hyperacute stage).

conservative management

Any management except from emergent carotid stenting (conservative management)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with stroke due to tandem occlusion in the anterior or posterior circulation, and patients with stroke due to isolated cervical artery occlusion, independently from previous thrombolysis, antiplatelet or anticoagulant use

You may qualify if:

• acute ischemic stroke
• tandem or isolated cervical artery occlusion (exploratory group)
• emergent extracranial vessel stenting or no stenting (treatment grouping variable)

You may not qualify if:

• hemorrhagic stroke
• no tandem occlusion and no isolated extracranial cervical vessel occlusion

Sponsors & Collaborators

• Azienda Unità Sanitaria Locale della Romagna: lead
• Hospital Universitari Vall d'Hebron Research Institute: collaborator
• Boston Medical Center: collaborator

Study Sites (3)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Bufalini Hospital Comprehensive Stroke Center

Cesena, 47521, Italy

Location

Vall d'Hebron Institut de Recerca

Barcelona, Spain

Location

Related Publications (3)

• Diana F, Abdalkader M, Behme D, Li W, Maurer CJ, Pop R, Hwang YH, Bartolini B, Da Ros V, Bracco S, Cirillo L, Marnat G, Katsanos AH, Kaesmacher J, Fischer U, Aguiar de Sousa D, Peschillo S, Zini A, Tomasello A, Ribo M, Nguyen TN, Romoli M; APT-eCAS collaboration. Antithrombotic regimen in emergent carotid stenting for acute ischemic stroke due to tandem occlusion: a meta-analysis of aggregate data. J Neurointerv Surg. 2024 Feb 12;16(3):243-247. doi: 10.1136/jnis-2023-020204.

  PMID: 37185107 BACKGROUND

• Diana F, Romoli M, Toccaceli G, Rouchaud A, Mounayer C, Romano DG, Di Salle F, Missori P, Zini A, Aguiar de Sousa D, Peschillo S. Emergent carotid stenting versus no stenting for acute ischemic stroke due to tandem occlusion: a meta-analysis. J Neurointerv Surg. 2023 May;15(5):428-432. doi: 10.1136/neurintsurg-2022-018683. Epub 2022 Apr 15.

  PMID: 35428740 BACKGROUND

• Romoli M, Molina CA, Zapata-Arriaza E, Jaikumar V, Jesser J, Heldner MR, Merlino G, Arba F, Giammello F, Radu RA, D'Anna L, Bigliardi G, Hanning U, Scarcia L, Puetz V, Abu Amara A, Zini A, Michel P, Aguiar De Sousa D, Al Kasab S, Casolla B, Kuhne Escola J, Da Ros V, Pezzini A, Candelaresi P, Alexandre AM, Toni D, Marto JP, Gabrieli JD, Sousa JA, Schwab R, Alpay K, Paciaroni M, Rapillo CM, Yeo L, Greisenegger S, Nolte CH, Caproni S, Anastasiou A, Tassi R, Maus V, Lattanzi S, Thanki SS, Sanna A, Naccarato M, Hawkes C, Abraham MG, Tudisco V, Requena M, Klein P, Ruggiero M, Lafe E, Medina-Rodriguez M, Monteiro A, Reiff T, Ringleb PA, Mohlenbruch M, Mujanovic A, Kaesmacher J, Peycheva M, Valente M, Taglialatela A, Toraldo F, Ferretti S, Toscano A, Ferrau L, Maffei S, Rosafio F, Schulte K, Kaiser D, Migliaccio L, Thevoz G, Soares MD, Abu Qdais A, Gardin A, Kohrmann M, Bellini L, Spina E, Andreone V, Nicolini E, Giacomozzi S, Sepe FN, Rosterman L, Aust A, Psychogios M, Selseth MN, Abdalkader M, Costalat V, Katsanos AH, Siddiqui AH, Longoni M, Tomasello A, Kristoffersen ES, Nguyen TN, Diana F; for CERES-TANDEM. Emergent Carotid Stenting for Acute Anterior Circulation Ischemic Stroke With Tandem Lesions: The Multicenter CERES-TANDEM Study. Neurology. 2026 Jan 27;106(2):e214528. doi: 10.1212/WNL.0000000000214528. Epub 2025 Dec 26.

  PMID: 41453121 DERIVED

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: May 11, 2025
• Study Start: January 1, 2018
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); US (1); IT (1)