Manipulation of Arterial Pressure in Acute Ischemic Stroke

Study Overview
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Brief Summary
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This is a controlled clinical trial among non thrombolysed acute ischemic stroke patients to determine the effects of three levels of arterial pressure on death and neurological disability. After the admission in the vascular unit of the Emergency Department the patients are randomized to maintain during the first 24h the Systolic Arterial Pressure in tree levels of pressure: 140 to 160 mmHg; 161 to 180 mmHg and 181 to 200 mmHg. The end point of the study is the Modified Rankin score and mortality in three month after the discharge.

Detailed Description
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To maintain the tree levels of systolic arterial pressure during de first 24h we will use one of the two strategies:1) infusion of 500 to 1000ml of saline solution and/or norepinephrine solution to increase de systolic pressure or 2) infusion of esmolol or nitroprussiate solution to decrease de pressure. Every patient will have a transcranial doppler study in the first 24h to measure the mean velocity of cerebral arteries.

Official Title
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Manipulation of Arterial Pressure Early in Non Thrombolysed Acute Ischemic Stroke: Effects on Death and Neurological Disability

Conditions
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Stroke, Acute

Intervention / Treatment
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* Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR)
* Drug: Esmolol, NPS or NOR
* Drug: manipulation of SAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years or older, with the first Acute Ischemic Stroke within the first 6 hours of the symptoms and not candidate to thrombolysis We will also include patients with previous Ischemic Stroke with Ranking score 0 or 1 Exclusion Criteria: Improuvment of the symptoms rapidly (in the first 15 min after admission) Seizures not related do the acute ischemic stroke Previous ischemic stroke in the last 6 weeks and with Ranking score > 1 Haemorrhagic stroke Anticoagulation Hypoglycemia Shock Acute heart failure

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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Accepts Healthy Volunteers

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1, 140 to 160 mmHg<br>Esmolol, NPS or NOR | Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR)<br>* Esmolol(2,5g /10ml + SG5% 240ml = 10mg/ml). Start with a bolus of 500mcg/kg in 1 min (ou 0,5mg/kg)and maintain the dose of 50mcg/kg/min (or 0,05mg/kg/min). Increase de infusion in 25mcg/kg/min after each 5 min until the randomized SAP or if the heart beat is lower than 60. The maximum dose is 200ug/kg/min (ou 0,2 mg/kg/min). If the randomized SAP do not reach the goal pressure with the maximum dose of esmolol, start a infusion of sodium nitroprussiate (NPS). NPS (50mg + SG5% 250ml= 200mcg/ml). No bolus. Start the infusion with 0,2 mcg/kg/min and maintain 0,5 a 5mcg/kg/min. Increase de dose each 15 min to a maximum of 10mcg/kg/min. NOR: (8mg/8ml + SG5% 242ml=32mcg/ml)No bolus. Start 1 to 5 mcg/min to a maximum dose of 20mcg/min.<br>* Other names: Esmolol, NPS or NOR;Drug: Esmolol, NPS or NOR<br>* We use one of the three drug to manipulate the systolic arterial pressure<br>Drug: manipulation of SAP<br>* Esmolol or NPS or NOR<br>* Other names: Esmolol or NPS or NOR;|
| Active Comparator: 2, 161 to 180 mmHg<br>Esmolol, NPS or NOR | Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR)<br>* Esmolol(2,5g /10ml + SG5% 240ml = 10mg/ml). Start with a bolus of 500mcg/kg in 1 min (ou 0,5mg/kg)and maintain the dose of 50mcg/kg/min (or 0,05mg/kg/min). Increase de infusion in 25mcg/kg/min after each 5 min until the randomized SAP or if the heart beat is lower than 60. The maximum dose is 200ug/kg/min (ou 0,2 mg/kg/min). If the randomized SAP do not reach the goal pressure with the maximum dose of esmolol, start a infusion of sodium nitroprussiate (NPS). NPS (50mg + SG5% 250ml= 200mcg/ml). No bolus. Start the infusion with 0,2 mcg/kg/min and maintain 0,5 a 5mcg/kg/min. Increase de dose each 15 min to a maximum of 10mcg/kg/min. NOR: (8mg/8ml + SG5% 242ml=32mcg/ml)No bolus. Start 1 to 5 mcg/min to a maximum dose of 20mcg/min.<br>* Other names: Esmolol, NPS or NOR;Drug: Esmolol, NPS or NOR<br>* We use one of the three drug to manipulate the systolic arterial pressure<br>Drug: manipulation of SAP<br>* Esmolol or NPS or NOR<br>* Other names: Esmolol or NPS or NOR;|
| Active Comparator: 3, 181 to 200 mmHg<br>Esmolol, NPS or NOR | Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR)<br>* Esmolol(2,5g /10ml + SG5% 240ml = 10mg/ml). Start with a bolus of 500mcg/kg in 1 min (ou 0,5mg/kg)and maintain the dose of 50mcg/kg/min (or 0,05mg/kg/min). Increase de infusion in 25mcg/kg/min after each 5 min until the randomized SAP or if the heart beat is lower than 60. The maximum dose is 200ug/kg/min (ou 0,2 mg/kg/min). If the randomized SAP do not reach the goal pressure with the maximum dose of esmolol, start a infusion of sodium nitroprussiate (NPS). NPS (50mg + SG5% 250ml= 200mcg/ml). No bolus. Start the infusion with 0,2 mcg/kg/min and maintain 0,5 a 5mcg/kg/min. Increase de dose each 15 min to a maximum of 10mcg/kg/min. NOR: (8mg/8ml + SG5% 242ml=32mcg/ml)No bolus. Start 1 to 5 mcg/min to a maximum dose of 20mcg/min.<br>* Other names: Esmolol, NPS or NOR;Drug: Esmolol, NPS or NOR<br>* We use one of the three drug to manipulate the systolic arterial pressure<br>Drug: manipulation of SAP<br>* Esmolol or NPS or NOR<br>* Other names: Esmolol or NPS or NOR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ranking score and mortality |  | Three month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Acute, Systolic Pressure of Blood