Manipulation of Arterial Pressure in Acute Ischemic Stroke (MAPAS)

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

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.

Study Overview

• Status: Unknown
• Conditions: Stroke, Acute
• Intervention / Treatment: Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR); Drug: Esmolol, NPS or NOR; Drug: manipulation of SAP

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil
      • Recruiting
      • Hospital de Clínicas de Porto Alegre/ UFRGS
      • Principal Investigator: L A Nasi, Doctor
      • Sub-Investigator: M Gus, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1, 140 to 160 mmHg; Esmolol, NPS or NOR	Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR); 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.; Other Names: Esmolol, NPS or NOR; Drug: Esmolol, NPS or NOR; We use one of the three drug to manipulate the systolic arterial pressure; Drug: manipulation of SAP; Esmolol or NPS or NOR; Other Names: Esmolol or NPS or NOR
ACTIVE_COMPARATOR: 2, 161 to 180 mmHg; Esmolol, NPS or NOR	Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR); 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.; Other Names: Esmolol, NPS or NOR; Drug: Esmolol, NPS or NOR; We use one of the three drug to manipulate the systolic arterial pressure; Drug: manipulation of SAP; Esmolol or NPS or NOR; Other Names: Esmolol or NPS or NOR
ACTIVE_COMPARATOR: 3, 181 to 200 mmHg; Esmolol, NPS or NOR	Drug: Esmolol, Sodium Nitroprussiate (NPS) or Norepinephrine (NOR); 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.; Other Names: Esmolol, NPS or NOR; Drug: Esmolol, NPS or NOR; We use one of the three drug to manipulate the systolic arterial pressure; Drug: manipulation of SAP; Esmolol or NPS or NOR; Other Names: Esmolol or NPS or NOR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ranking score and mortality	Three month

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Luiz A Nasi, Physician, Hospital de Clínicas de Porto Alegre / UFRGS

Publications and helpful links

General Publications

• Potter J, Robinson T, Ford G, James M, Jenkins D, Mistri A, Bulpitt C, Drummond A, Jagger C, Knight J, Markus H, Beevers G, Dewey M, Lees K, Moore A, Paul S; CHHIPS Trial Group. CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design. J Hypertens. 2005 Mar;23(3):649-55. doi: 10.1097/01.hjh.0000160224.94220.e7.

Helpful Links

• Clinical trial of Manipulation of Arterial Pressure Early in Acute Ischemic Stroke

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ANTICIPATED): December 1, 2010
• Study Completion (ANTICIPATED): December 1, 2010

Study Registration Dates

• First Submitted: February 19, 2009
• First Submitted That Met QC Criteria: February 19, 2009
• First Posted (ESTIMATE): February 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 31, 2009
• Last Update Submitted That Met QC Criteria: December 30, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: Stroke, Acute; Systolic Pressure of Blood
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Antagonists; Vasoconstrictor Agents; Norepinephrine; Esmolol
• Other Study ID Numbers: HCPA 07-470