CardioLogical Interventions and Acute strOke Treatment sTudy

CLOT is a multicenter, observational, ambispective real-world study involving acute ischemic stroke cases occuring after cardiological procedures.

Patients will be recruited at different emergency services and stroke units in Europe. The study will encompass a retrospective (CLOT-R) and prospective (CLOT-P) data collection.

CLOT-R will include cases the occured in the 5 years befor the initation of the study; CLOT-P has a duration of 2 years of enrollement from the study approval at each site and follow-up of 180 days (total duration of 2 years and 180 days). The inclusion criteria are: acute ischemic stroke in adult patient (18 years of age or older) as diagnosed according to the World Health Organization (WHO) criteria; stroke with evidence of CT/MRI DWI/FLAIR acute lesion in the first neuroimaging or in the follow-up at 24-48 h; interventional cardiological procedures performed within 28 days since the stroke onset (Percutaneuous Coronary Intervention - PCI, Transcatheter Aortic Valve Replacement - TAVR, Baloon Aortic Valvuloplasy - BAV, Percutaneous Mitral Valve Repair or Replacement, Patent Formaen Ovale - PFO - or Atrial Septal Defects - ASD - Closure, Left Atrial Appendage Closure, Transcatheter Pulmonary Valve Replacement, Percutaneous Closure of Paravalvular Leaks); written informed consent provided by the patient himself or by proxy (for unconscious patients, cognitively impaired, or aphasic).

Exclusion criteria are: Stroke-like symptoms due primarily to another non-ischemic/hemorrhagic acute neurological condition or stroke mimics (e.g. severe hypo- or hyperglycemia, migraine with aura, functional disorders, etc); Spontaneous and post traumatic hemorrhagic stroke or spontaneous/post-traumatic subarachnoid hemorrhage or subdural hematoma; Impossibility to achieve written informed consent.

The primary outcome of CLOT-R is a descriptive analysis of baseline demographic, clinical, neuroimaging, cardiological procedural and acute stroke treatment characteristics. The secondary outcomes are: effectiveness and safety of intravenous thrombolysis (IVT) with or without mechanical thrombectomy (MT), or MT alone; 90-day post-stroke risk of all-cause and vascular mortality, new ischemic stroke or transient ischemic attack (TIA), myocardial infarction, intracranial hemorrhage or other major bleeding events, disability as measured by the modified Rankin Scale (mRS) score.

The primary outcome of CLOT-P is effectiveness and safety of IVT with or without MT, or MT alone. The secondary outcomes are 90-day and 180-day post-stroke risk of all-cause and vascular mortality, new ischemic stroke or TIA, myocardial infarction, intracranial hemorrhage or other major bleeding events, disability as measured by the mRS score.

The statistic analyses will include Descriptive statistics (baseline characteristics), Poisson regression analysis (incidence of primary and secondary outcomes at each timepoint), Cox regression analysis (time-to-outcomes comparison between groups, identification of outcomes predictors), generalized linear regression (ordinal mRS distribution comparison between maintainers and switchers), risk ratio and risk difference calculation for primary and secondary outcomes comparison (unadjusted and adjusted for confounders), pseudo-randomization (propensity score matching or inverse probability weighting).

The study aims to include in CLOT-P a minimum sample of 400 patients (100 patients for each acute stroke treatment group and 100 untreated) to have reliable estimates of the primary study outcome.

• CLOT-R secondary outcome - Efficacy [Time frame: 90-day follow-up]
• CLOT-R secondary outcome - Safety [Time frame: 90-day follow-up]
• CLOT-R secondary outcome: Serious Adverse Event (SAE) [Time frame: 90-day follow-up]
• CLOT-P secondary outcome: Serious Adverse Event (SAE) [Time frame: 90-day and 180-day follow-up]