Cerebral large vessel occlusion stroke multiomics biosample cohort (CLOMB): a multicentre cohort protocol.

BACKGROUND: Acute ischaemic stroke with large vessel occlusion (AIS-LVO) is a significant subtype of ischaemic stroke which always requires endovascular treatment (EVT). Although EVT has a high recanalisation rate, nearly 40% of AIS-LVO patients experience futile recanalisation. Studying the occlusion microenvironment (OME), comprising thrombus and intracranial arterial blood, is essential to understand the localised markers of stroke and futile recanalisation. DESIGN: Cerebral Large Vessel Occlusion Stroke Multiomics Biosample Cohort (CLOMB) is a multicentre, multiomics ambispective cohort study conducted in five stroke centres in China. A total of 500 patients with AIS-LVO who undergo EVT will be included in the study. After enrolment, each participant undergoes a comprehensive clinical assessment including questionnaires, physical examinations, laboratory tests and imaging. We collect matched peripheral (arterial and venous) blood, thrombus and innovatively intracranial blood by microcatheter or aspiration catheter when first passing through the occlusion site. All biosamples are collected for subsequent multi-omics analysis (metabolomic, proteomic and transcriptomic). A 3-month and 1-year follow-up will be performed to collect the outcome data. METHODS: Systemic and local samples undergo untargeted metabolomic and proteomic analysis. For a representative subset (10%-15%), single-cell RNA sequencing (Switching Mechanism at 5' End of the RNA Transcript) is performed. Targeted omics will be selectively implemented to further clarify their contents. To minimise selection bias, patients without retrieved thrombi remain in the cohort for clinical analysis. CONCLUSION: CLOMB establishes a standardised protocol for OME biosampling and multiomics profiling. It aims to explore candidate biological pathways and provide a foundation for developing hypothesis-generating models for improving stroke outcomes, facilitating AIS-LVO diagnosis and classification. TRIAL REGISTRATION NUMBER: NCT06963489.