Intensive Ambulance-delivered Blood Pressure Reduction in Hyper-Acute Stroke Trial

Study Overview
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Brief Summary
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A multicentre, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) study to assess the effects of hyperacute intensive blood pressure (BP) lowering initiated in ambulance setting on (i) functional outcome in patients with acute stroke (ii) safety in patients with confirmed acute stroke and other conditions that were initially suspected as acute stroke (i.e. stroke mimic).

Detailed Description
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As an investigator initiated and conducted, multicentre, ambulance-delivered, prospective, randomised, open-label, blinded outcome (PROBE) study. INTERACT4 aims to evaluate the effects of functional outcome according to an ordinal analysis of the full range of scores on the mRS, the safety in all randomised patients; reperfusion treatment (thrombolysis and/or thrombectomy) related symptomatic ICH (sICH, according to standard definitions), infarct size, the time to and overall rate of reperfusion treatment in AIS patients; hematoma volume and early expansion in ICH.

Official Title
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Intensive Ambulance-delivered Blood Pressure Reduction in Hyper-Acute Stroke Trial

Conditions
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Cerebrovascular Disorders, Stroke, Acute

Intervention / Treatment
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* Drug: urapidil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥18 years; Acute syndrome that is due to presumed acute stroke, defined as FAST（Face, Arm, Speech, Time） scores of ≥2 with an arm motor deficit and time ≤2 hours from last seen well; Systolic BP ≥150 Able to provide brief informed consent (if a waver of consent is not approved by the ethics committee) Exclusion Criteria: Coma - no response to tactile stimuli or verbal stimuli; Severe co-morbid disease (e.g. cancer, chronic airflow disease, severe dementia,severe heart failure,pre-stroke disability[needed help]); History of epilepsy or seizure at onset; History of recent head injury (<7 days); Hypoglycemia(glucose<2.8mmol/L)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: central randomization with stratification
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>If systolic blood pressure>180:IV Urapidil 25mg If systolic blood pressure>150 (or 5 mins after first bolus) : IV Urapidil 25mg and to maintain this level after admission to hospital in those with confirmed acute stroke for the next 7 days (or hospital discharge if earlier) | Drug: urapidil<br>* A standard treatment regime based on intravenous (IV) bolus of 25mg urapidil administered over 1 minute. For those patients initial systolic blood pressure 180, another 25mg urapidil bolus will be given if the systolic blood pressure level persists >150 after 5 minutes.<br>* Other names: Intensive BP lowing;|
| No Intervention: control group<br>To receive blood pressure management according to standard local guidelines which recommend blood pressure lowering in hospital if systolic level is >220mmHg. This level will be considered by ambulance staff as a threshold for treatment if considered clinically important. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| level of physical function | Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with serious adverse events | total number of serious adverse events reported during follow-up, according to standard definitions | Day 90 | 
| number of patients with any intracranial hemorrhage | reperfusion treatment (thrombolysis/thrombectomy) related symptomatic intracerebral number of cases of intracranial hemorrhage, according to standard definitions | Day 7 | 
| size of cerebral infarction | overall size of cerebral infarction on MRI within 2 days in cases of ischaemic stroke | Day 2 | 
| number of patients who receive reperfusion treatment | total number of cases of reperfusion (thrombolysis and/or thrombectomy) in ischemic stroke | Day 0 | 
| time to use of reperfusion treatment | time from symptom onset to reperfusion treatment in patients with ischemic stroke | Day 0 | 
| size of hematoma volume | change in volume of hematoma from baseline to 24 hours, measured on brain imaging | Day 1 | 
| size of hematoma volume | volume of hematoma at baseline measured on brain imaging | Day 0 | 
| death or major disability | Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. mRS(3-6) | Day 90 | 
| Death |  | Day 90 | 
| Disability | Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. | Day 90 | 
| death or dependency measured by a shift in NIHSS |  | day 1 and day 7 | 
| Health related quality of life | according to the EQ-5D | day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, blood pressure control, hypertension, clinical trial, ambulances