Remote Ischemic Conditioning in Patients With Acute Stroke (RESIST)

Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors.

the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death)

If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency.

• If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made.
• If disagreement occurs between one face-to-face assessment and one telephone assessment

• the face-to-face will be considered the final assessment
• If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Neurological deficits are documented using Prehospital Stroke Score (PreSS). Prehospital Stroke Score is assessed in the the ambulance and at 24-hour or at discharge (if discharge occurs before 24 hours). The PreSS score consists of the Cincinnati Prehospital Stroke Scale (CPSS) with an additional opportunity to report other neurological symptoms (e.g. ataxia, sensory disturbances and visual field loss), and PASS (Prehospital Acute Stroke Severity Scale). The PreSS score range from 0-6, with 6 representing the most severe neurological deficits.

Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). TThe assessment will performed by two independent telephone or face-to-face assessors.

the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency.

If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made.

If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Clinical outcome (modified Rankin Scale) at 3 months inacute ischemic stroke receiving reperfusion therapy (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors.

the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency.

If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made.

If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Clinical outcome (modified Rankin Scale) at 3 months in patients with intracerebral hemorrhage (ICH) (generalized ordinal logistic regression).

The assessment will performed by two independent telephone or face-to-face assessors.

the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency.

If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made.

If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Difference in proportion of patients with complete remission of symptoms within 24 hours (TIA; both with and without DWI) Diagnosis of TIA is documented in the electronic case report form

MACCE is defined as: Cardiovascular events (cardiovascular death, myocardial infarction, acute ischemic or hemorrhagic stroke)

Cardiovascular death: Death from known cardiovascular cause or sudden death from unknown cause (no identified cause of death in medical history and/or autopsy)

Acute myocardial infarction: Admission with a discharge diagnosis of ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP)

Stroke: Admission with a discharge diagnosis of acute ischemic or hemorrhagic stroke. Evaluation is performed using the Danish National Patient Register (LPR) and the DSR at two time points (6 and 15 months after the inclusion of the last patient).

Diagnosis of AIS/TIA, ICH and MI (STEMI, NSTEMI, and UAP) are made according to national clinical practice guidelines.

Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function.

Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function.

Quality of life (WHO-5 Well-Being Index) measures in AIS and ICH patients at 3 months

Bed-day use, measured at 3 months, in AIS and ICH patients

All-cause mortality is assessed and subdivided into cardiovascular mortality versus non-cardiovascular mortality

Clinical outcome [modified Rankin Scale (mRS) at 3 months in ischemic stroke patients and the extended remote ischemic postconditioning protocol Ordinal logistic regression analysis will be performed.The assessment will performed by two independent telephone or face-to-face assessors.

the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency.

If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made.

If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Clinical outcome (modified Rankin Scale (mRS) at 3 months in intracerebral hemorrhage patients and the extended remote ischemic postconditioning protocol The assessment will performed by two independent telephone or face-to-face assessors.

the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency.

If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made.

If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Proportion of RIC treated AIS patients with large vessel occlusion (LVO) eligible to EVT treatment compared to standard treatment, adjusted for prehospital stroke severity (PreSS) and symptom duration

• Severe Stroke (NIHSS ≥ 10)
• Groin puncture feasible within 6 hours from stroke onset
• MRI-time-of-flight (TOF) documented internal carotid artery (ICA), Intracranial ICA (ICA-T) and first and second stem of the middle cerebral artery (M1 and M2, respectively)
• No contraindications to MRI (pacemaker, vomiting, respiratory insufficiency, obesity)
• MRI-Diffusion weighted imaging (DWI) lesion volume ≤ 70 mL

24-hour infarct growth on DWI-MRI (Difference in lesion volume between acute and 24-hour DWI-MRI) (Substudy at Aarhus University Hospital)

24-hour hematoma growth (Difference in hematoma volume between acute and 24-hour CT/MRI) (Substudy at Aarhus University Hospital)

7-day hematoma reduction (Difference in hematoma volume between acute and 7-day (day 5 to 9) CT ) (Substudy at Aarhus University Hospital)

Ektacytometry for Erythrocytic Deformability and Analytical Flow Cytometry (FC) for eryNOS3 phosphorylation (pNOS3Ser1177) and s-nitrosylation (-SNO) in RBC

MicroRNA and extracellular vesicle characterization of a possible RIC treatment profile (substudy at Aarhus University Hospital)

Diagnostic abilities of a prehospital microRNA and extracellular vesicles blood samples profile combined with prehospital stroke severity on the differentiation of hemorrhagic from ischemic stroke and to grade ischemic stroke severity

Predictive abilities of Glial Fibrillary Acidic Protein (GFAP) in prehospital obtained blood samples combined with prehospital stroke severity to differentiate hemorrhagic from ischemic stroke and to grade ischemic stroke severity

Functional and immunologic plasma assays will be employed to analyze proteins and pathways in coagulation and fibrinolysis (substudy at Aarhus University Hospital)