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Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

Primary Purpose

Intracerebral Hemorrhage, Hypertension, Stroke

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
nicardipine
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intracerebral Hemorrhage focused on measuring cerebral hemorrhage, intracerebral hemorrhage, stroke, hypertension, blood pressure, nicardipine, antihypertensive agent, hematoma expansion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age older than 18 years.
  • Onset of new neurological signs of a stroke within 12 hours of the time to evaluation AND initiation of treatment with intravenous nicardipine.
  • Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
  • The total GCS score is greater than 8 at the time of enrollment.
  • CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement less than 60 cc.
  • ICH is supratentorial and is located in lobar, basal ganglionic, or thalamic based on the initial CT scan appearance.
  • Admission systolic blood pressure greater than 170 mm Hg on two repeat measurements at least 5 minutes apart.
  • Evidence of chronic hypertension.
  • Subject is not considered a surgical candidate by the neurosurgery service.

Exclusion Criteria:

  • Time of symptom onset cannot be reliably assessed.
  • Previously known neoplasms, arteriovenous malformation, or aneurysms.
  • Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon.
  • ICH is located in the cortex or infratentorial regions such as pons or cerebellum.
  • Blood is visualized in the subarachnoid space.
  • Intravenous nicardipine cannot be initiated within 12 hours of symptom onset.
  • Use of clonidine hydrochloride and other central alpha-agonist within the last 48 hours that have the potential of withdrawal hypertension.
  • Pregnancy, lactation, or parturition within previous 30 days.
  • Any history of bleeding diathesis or coagulopathy, including the use of warfarin.
  • Use of heparin in the previous 48 hours and a prolonged partial thromboplastin time.
  • Known atrial-ventricular heart block other than first degree, or sick sinus syndrome without a pacemaker.
  • Intolerance to calcium channel blockers.
  • Exposure to study medication in the preceding 24 hours prior to enrollment.
  • A platelet counts less than 100 000/mm3.
  • Major surgery within the previous six weeks.
  • History of any intracranial hemorrhage (including intracerebral or subarachnoid hemorrhage) or hemorrhagic stroke.
  • Seizure at onset of stroke.
  • Blood glucose less than 50 mg/dL or greater than 400 mg/dL.
  • Current participation in another research drug treatment protocol.
  • Isolated ventricular blood on CT scan.
  • Subject has a living will that precludes aggressive intensive care unit management.
  • Subject has acute myocardial infarction or renal failure that precludes use of aggressive antihypertensive therapy.
  • Subjects with unstable angina or acute myocardial infarction within 2 weeks prior to ICH.
  • Subjects with renal insufficiency with serum creatinine greater than 2.0 mg/dl or on renal dialysis.
  • Sinus tachycardia exceeding 120 beats per minute or supraventricular tachycardia is observed during initial evaluation.
  • Ischemic stroke within 4 weeks of presentation.
  • Congestive heart failure graded as class III and IV by New York Heart Association (NYHA) classification.

Sites / Locations

  • University of Southern California
  • Kansas University Medical Center
  • The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center
  • Massachusetts General/Brigham Women's Hospital
  • Clinical Coordinating Center: University of Minnesota, Fairview Hospital
  • Saint Louis University
  • JFK Medical Center
  • University of Medicine and Dentistry of New Jersey
  • Columbia University Medical Center
  • Case Western Reserve University
  • Ohio State University
  • Statistical Coordinating Center: Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Tier 1

Tier 2

Tier 3

Arm Description

Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 170 to 200 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 140 to 170 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 110 to 140 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Outcomes

Primary Outcome Measures

Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
Feasibility of treatment was assessed by whether SBP reduction and maintenance within the respective target range was achieved (treatment success) or not (treatment failure), and secondarily by whether a significant difference between treatment arms was achieved. Treatment failure was defined based on the observed hourly hourly minimum SBP remaining greater than the upper limit of the target range for 2 consecutive hours after initiation of nicardipine infusion. Spontaneous decline of SBP below the lower limit of the specific tier was not considered treatment failure as all such declines were asymptomatic.The lower number in the more intensive treatment groups reflects in part the greater challenge of rapidly lowering systolic blood pressure to a more intensive (lower) range, as a higher number of treatment failures as pre-defined by meeting the SBP range goal within 3 hours of symptom onset in this group predictably occurred.
Number of Participants With Neurological Deteriorations (Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score) During the 24 Hour Treatment",
Neurological status was monitored quantitatively and independently of other adverse events using two scales. The Glasgow Coma Scale (GCS) score measures level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired. The National Institutes of Health Stroke Scale (NIHSS) quantifies neurologic deficits in 11 categories. Level of consciousness, horizontal eye movements, visual fields, facial palsy, movement in each limb, sensation, language and speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42; 0 indicates normal function and higher scores indicate greater deficit severity.
Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject
Serious adverse events were ascertained by site investigators using FDA-defined guidelines, defined as any untoward clinical events having been fatal, life-threatening, resulting in new or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage. Subjects were followed closely from randomization through 90 days. The initial 72-hour period was chosen as the most meaningful time period for which to examine SAEs likely to be related to the acute safety of the study treatment.

Secondary Outcome Measures

Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects

Full Information

First Posted
December 21, 2006
Last Updated
November 17, 2017
Sponsor
University of Minnesota
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT00415610
Brief Title
Antihypertensive Treatment in Acute Cerebral Hemorrhage
Acronym
ATACH
Official Title
Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this trial is to evaluate the safety and effectiveness of lowering blood pressure using nicardipine in persons with acute hypertension associated with intracerebral hemorrhage.
Detailed Description
An estimated 37,000 to 52,400 people in the United States have intracerebral hemorrhage (ICH) every year. ICH--a form of stroke that has poor outcome and is difficult to treat--is associated with the highest mortality rate of all strokes. Hematoma expansion has been identified as the most common cause of neurological deterioration in persons with ICH. Early evidence suggests that acute hypertension (HTN)-or elevated blood pressure-may make some individuals more susceptible to hematoma expansion. Treating HTN acutely may prevent hematoma expansion, however, the effect of aggressive HTN treatment has not been determined. The purpose of this trial is to evaluate the treatment feasibility and safety of lowering blood pressure using nicardipine--an antihypertensive medication--in persons who have acute HTN associated with ICH. This pilot study will enroll 60 individuals who qualify with a presenting systolic blood pressure of at least 170 mmHg, have an ICH, and can be evaluated and treatment initiated within 6 hours of onset of stroke symptoms. In a stepwise fashion, the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 3 sequential levels: 170 to 200 mmHg, 140 to 170 mmHg, and 110 to 140 mmHg. Twenty participants will be enrolled per level. Treatment will last 18 to 24 hours. Participants will stay in the hospital for about 7 days (including 24 hours in the intensive care unit for close monitoring) and will return for 1-hour follow-up visits at 30 days and at 90 days after discharge from the hospital. During these visits participants will receive neurological assessments to determine their functional outcome. For participants, the study will be completed after the 90-day follow-up visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracerebral Hemorrhage, Hypertension, Stroke
Keywords
cerebral hemorrhage, intracerebral hemorrhage, stroke, hypertension, blood pressure, nicardipine, antihypertensive agent, hematoma expansion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Staged intensity levels of rapid intravenous antihypertensive control for elevated SBP in patients with intracerebral hemorrhage were implemented in 3 sequential treatment arms to assess the feasibility and tolerability (safety) of this treatment.
Masking
None (Open Label)
Masking Description
Open treatment assignment was employed because it is not safe to conceal SBP measurement. Patient data routinely entered by clinical staff were used to evaluate safety.
Allocation
Non-Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tier 1
Arm Type
Other
Arm Description
Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 170 to 200 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.
Arm Title
Tier 2
Arm Type
Other
Arm Description
Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 140 to 170 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.
Arm Title
Tier 3
Arm Type
Other
Arm Description
Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 110 to 140 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.
Intervention Type
Drug
Intervention Name(s)
nicardipine
Other Intervention Name(s)
Cardene, nicardipine hydrochloride
Intervention Description
Intravenous (IV) nicardipine infusion. It is expected that the treatment duration will vary between 18 and 24 hours. Started at 5mg/h Titrated by 2.5mg/hour every 15 minutes to bring systolic blood pressure in target range for the applicable Tier. Max dose 15mg/hour *Once target systolic blood pressure reached, dose decreased by 2.5mg/hour every 15 minutes until systolic blood pressure maintained in the target range or the medication is discontinued.
Primary Outcome Measure Information:
Title
Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
Description
Feasibility of treatment was assessed by whether SBP reduction and maintenance within the respective target range was achieved (treatment success) or not (treatment failure), and secondarily by whether a significant difference between treatment arms was achieved. Treatment failure was defined based on the observed hourly hourly minimum SBP remaining greater than the upper limit of the target range for 2 consecutive hours after initiation of nicardipine infusion. Spontaneous decline of SBP below the lower limit of the specific tier was not considered treatment failure as all such declines were asymptomatic.The lower number in the more intensive treatment groups reflects in part the greater challenge of rapidly lowering systolic blood pressure to a more intensive (lower) range, as a higher number of treatment failures as pre-defined by meeting the SBP range goal within 3 hours of symptom onset in this group predictably occurred.
Time Frame
Within 3 hours of symptom onset and sustained through 18-24 hours.
Title
Number of Participants With Neurological Deteriorations (Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score) During the 24 Hour Treatment",
Description
Neurological status was monitored quantitatively and independently of other adverse events using two scales. The Glasgow Coma Scale (GCS) score measures level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired. The National Institutes of Health Stroke Scale (NIHSS) quantifies neurologic deficits in 11 categories. Level of consciousness, horizontal eye movements, visual fields, facial palsy, movement in each limb, sensation, language and speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42; 0 indicates normal function and higher scores indicate greater deficit severity.
Time Frame
within the first 72 hours of treatment initiation
Title
Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject
Description
Serious adverse events were ascertained by site investigators using FDA-defined guidelines, defined as any untoward clinical events having been fatal, life-threatening, resulting in new or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage. Subjects were followed closely from randomization through 90 days. The initial 72-hour period was chosen as the most meaningful time period for which to examine SAEs likely to be related to the acute safety of the study treatment.
Time Frame
from treatment initiation through 72 hours
Secondary Outcome Measure Information:
Title
Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
Description
The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects
Time Frame
3 months
Other Pre-specified Outcome Measures:
Title
Particpants Who Achieve Reduction of Blood Pressure and Maintain Treatment Goals (the Specified Systolic Blood Pressure Range for the 18-24 Hour Period) Without Neurological Deterioration or Side Effects Resulting in Death.
Description
The tolerability of the study treatment was further ascertained by examination of in-hospital, 1-month, or 3-month mortality in each treatment group. This pilot study was not powered (did not plan to enroll an adequate number of patients) to draw meaningful conclusions about individual adverse event categories, outcome measures, or to make comparisons between the treatment arms beyond the overall feasibility and tolerability of rapidly and significantly lowering SBP following intracerebral hemorrhage. The timing and magnitude of SBP reduction was also compared to the timing of individual safety events to further evaluate possible relationships between the study treatment, adverse events, and any recognizable safety concerns. This information is available in publication but is not able to be displayed on this website due to formatting restrictions.
Time Frame
From enrollment through 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age older than 18 years. Onset of new neurological signs of a stroke within 12 hours of the time to evaluation AND initiation of treatment with intravenous nicardipine. Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect. The total GCS score is greater than 8 at the time of enrollment. CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement less than 60 cc. ICH is supratentorial and is located in lobar, basal ganglionic, or thalamic based on the initial CT scan appearance. Admission systolic blood pressure greater than 170 mm Hg on two repeat measurements at least 5 minutes apart. Evidence of chronic hypertension. Subject is not considered a surgical candidate by the neurosurgery service. Exclusion Criteria: Time of symptom onset cannot be reliably assessed. Previously known neoplasms, arteriovenous malformation, or aneurysms. Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon. ICH is located in the cortex or infratentorial regions such as pons or cerebellum. Blood is visualized in the subarachnoid space. Intravenous nicardipine cannot be initiated within 12 hours of symptom onset. Use of clonidine hydrochloride and other central alpha-agonist within the last 48 hours that have the potential of withdrawal hypertension. Pregnancy, lactation, or parturition within previous 30 days. Any history of bleeding diathesis or coagulopathy, including the use of warfarin. Use of heparin in the previous 48 hours and a prolonged partial thromboplastin time. Known atrial-ventricular heart block other than first degree, or sick sinus syndrome without a pacemaker. Intolerance to calcium channel blockers. Exposure to study medication in the preceding 24 hours prior to enrollment. A platelet counts less than 100 000/mm3. Major surgery within the previous six weeks. History of any intracranial hemorrhage (including intracerebral or subarachnoid hemorrhage) or hemorrhagic stroke. Seizure at onset of stroke. Blood glucose less than 50 mg/dL or greater than 400 mg/dL. Current participation in another research drug treatment protocol. Isolated ventricular blood on CT scan. Subject has a living will that precludes aggressive intensive care unit management. Subject has acute myocardial infarction or renal failure that precludes use of aggressive antihypertensive therapy. Subjects with unstable angina or acute myocardial infarction within 2 weeks prior to ICH. Subjects with renal insufficiency with serum creatinine greater than 2.0 mg/dl or on renal dialysis. Sinus tachycardia exceeding 120 beats per minute or supraventricular tachycardia is observed during initial evaluation. Ischemic stroke within 4 weeks of presentation. Congestive heart failure graded as class III and IV by New York Heart Association (NYHA) classification.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adnan I. Qureshi, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Kansas University Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Massachusetts General/Brigham Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Clinical Coordinating Center: University of Minnesota, Fairview Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Saint Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
JFK Medical Center
City
Edison
State/Province
New Jersey
ZIP/Postal Code
08818
Country
United States
Facility Name
University of Medicine and Dentistry of New Jersey
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07107
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Statistical Coordinating Center: Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
consult investigator for options
Citations:
PubMed Identifier
17356194
Citation
Qureshi AI. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design. Neurocrit Care. 2007;6(1):56-66. doi: 10.1385/ncc:6:1:56.
Results Reference
background
PubMed Identifier
20457956
Citation
Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz-Flores S, Ehtisham A, Ezzeddine MA, Goldstein JN, Hussein HM, Suri MF, Tariq N; Antihypertensive Treatment of Acute Cerebral Hemorrhage Study Investigators. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol. 2010 May;67(5):570-6. doi: 10.1001/archneurol.2010.61.
Results Reference
result
PubMed Identifier
19770736
Citation
Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators. Antihypertensive treatment of acute cerebral hemorrhage. Crit Care Med. 2010 Feb;38(2):637-48. doi: 10.1097/CCM.0b013e3181b9e1a5.
Results Reference
result
PubMed Identifier
18606927
Citation
Qureshi AI. Acute hypertensive response in patients with stroke: pathophysiology and management. Circulation. 2008 Jul 8;118(2):176-87. doi: 10.1161/CIRCULATIONAHA.107.723874. No abstract available.
Results Reference
result
PubMed Identifier
22560810
Citation
Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz Flores S, Ehtisham A, Goldstein JN, Kirmani JF, Hussein HM, Suri MF, Tariq N; Antihypertensive Treatment of Acute Cerebral Hemorrhage Investigators. Systolic blood pressure reduction and risk of acute renal injury in patients with intracerebral hemorrhage. Am J Med. 2012 Jul;125(7):718.e1-6. doi: 10.1016/j.amjmed.2011.09.031. Epub 2012 May 4.
Results Reference
result
PubMed Identifier
21626077
Citation
Qureshi AI, Palesch YY. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: design, methods, and rationale. Neurocrit Care. 2011 Dec;15(3):559-76. doi: 10.1007/s12028-011-9538-3.
Results Reference
result
PubMed Identifier
23233387
Citation
Hussein HM, Tariq NA, Palesch YY, Qureshi AI; ATACH Investigators. Reliability of hematoma volume measurement at local sites in a multicenter acute intracerebral hemorrhage clinical trial. Stroke. 2013 Jan;44(1):237-9. doi: 10.1161/STROKEAHA.112.667220. Epub 2012 Dec 11.
Results Reference
derived

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Antihypertensive Treatment in Acute Cerebral Hemorrhage

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