Clinical trial NCT01176565: Antihypertensive Treatment of Acute Cerebral Hemorrhage-II
Official title: Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-II: A Phase III Randomized Multicenter Clinical Trial of Blood Pressure Reduction for Hypertension in Acute Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Intracerebral Hemorrhage
Keywords: Acute hypertensive response
intracerebral hemorrhage
blood pressure
outcome
nicardipine
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Medical University of South Carolina
name: Johns Hopkins University
name: University of Michigan
name: Neurocritical Care Research Network
name: National Cerebral and Cardiovascular Center, Japan
name: Japan Cardiovascular Research Foundation
name: Beijing Tiantan Hospital
name: China Medical University Hospital
name: University Hospital Heidelberg
name: Seoul National University Hospital
First posted: 2010-08-06
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients are randomized 1:1 via computer-generated treatment assignment within 4.5 hours of neurological symptom onset to either standard or intensive SBP management using intravenous nicardipine hydrochloride as the primary BP control agent through 24 hours from randomization. Enrolled patients from both treatment arms are otherwise treated similarly after 24 hours, according to their medical needs. Standards of care management for spontaneous intracerebral hemorrhage published in the 2010 American Heart Association guidelines are incorporated in to the study protocol. All enrolled patients are followed through 90 days (± 14 days per protocol window; up to ± 30 days data is used) unless death or withdrawal occurs sooner. Primary analysis based on intent-to-treat (ITT) principles.
Primary purpose: TREATMENT

Brief summary: The specific aims of this study are to:

1. Definitively determine the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of patients with death and disability (mRS 4-6) at 3 months among subjects with ICH who are treated within 4.5 hours of symptom onset.
2. Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the subjects' quality of life as measured by EuroQol at 3 months.
3. Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of hematoma expansion (defined as increase from baseline hematoma volume of at least 33%) and in the change from baseline peri-hematoma volume at 24 hours on the serial computed tomographic (CT) scans.
4. Assess the safety of the intensive treatment relative to the standard treatment in the proportion of subjects with treatment-related serious adverse events (SAEs) within 72 hours.

Detailed description: The report from a National Institute of Neurological Disorders and Stroke Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) in December 2003 recommended clinical trials for evaluation of blood pressure (BP) management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertension in ICH. Consequently, we propose to conduct a five-year international, multicenter, open-labeled, randomized, controlled, Phase III trial to determine the efficacy of early, intensive antihypertensive treatment using intravenous nicardipine for acute hypertension in subjects with co-morbid hypertension and spontaneous supratentorial ICH. The primary hypothesis of this large, streamlined, focused trial is that the group treated with intensive BP reduction (systolic BP \[SBP\] of 140 mmHg or less - hereafter referred to as the intensive treatment) using intravenous nicardipine infusion for 24 hours reduces the proportion of death and disability at 3 months by 10% or greater compared with the group treated with the standard BP reduction (SBP of 180 mmHg or less - hereafter referred to as the standard treatment) among patients with ICH treated within 4.5 hours of symptom onset. The underlying mechanism for this expected beneficial effect of intensive treatment is mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 38% of patients with acute ICH. The trial will recruit a maximum of 1,280 subjects with ICH who meet the eligibility criteria. The primary outcome is the proportion of death and disability at 3 months defined by modified Rankin scale (mRS) score of 4 to 6. The proposed clinical trial is the natural extension of numerous case series, a subsequent pilot trial funded by the National Institutes of Health National Institute of Health (NIH), and a preliminary randomized controlled trial in this patient group funded by the Australian National Health and Medical Research Council, that have recently confirmed the safety and tolerability of both the regimen and goals of the antihypertensive treatment in acutely hypertensive patients with ICH proposed in the present trial. The proposed trial will have important public health implications by providing necessary information regarding the efficacy and safety of antihypertensive treatment of acute hypertension observed in up to 75% of the subjects with ICH. BP treatment represents a strategy that can be made widely available without the need of specialized equipment and personnel and therefore can make a major impact upon outcome in patients with ICH. Substantial reduction in morbidity and mortality appears possible if the estimates of treatment effect sizes from current pilot trials are accurate.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* IV nicardipine can be initiated within 4.5 hours of symptom onset.
* Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
* Total Glasgow Coma Scale (GCS) score (aggregate of verbal, eye, and motor response scores) of 5 or greater at time of emergency department (ED) arrival.
* International normalized ratio (INR) value \< 1.5
* CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement \<60 cc.
* For subjects randomized prior to IV antihypertensive administration: SBP greater than 180 mmHg\* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT spontaneous SBP reduction to below 180 mmHg at the time of randomization OR
* For subjects randomized after IV antihypertensive administration: SBP greater than 180 mmHg\* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT SBP reduction to below 140 mmHg at the time of randomization.
* Informed consent obtained by subject, legally authorized representative, or next of kin.

  * Notes: The unit "mmHg" stands for "millimeters of mercury", a standard way of measuring blood pressure. Patients with SBP \< 180 mmHg should be monitored for 4.5 hours from symptom onset as their SBP may rise to eligible levels before the eligibility window closes.

Exclusion Criteria:

* ICH is due to previously known neoplasms, arteriovenous malformation (AVM), or aneurysms.
* Intracerebral hematoma considered to be related to trauma.
* ICH located in infratentorial regions such as pons or cerebellum.
* Intraventricular hemorrhage (IVH) associated with intraparenchymal hemorrhage and blood completely fills one lateral ventricle or more than half of both ventricles.
* Patient to receive immediate surgical evacuation.
* Current pregnancy, or parturition within previous 30 days, or active lactation.
* Use of dabigatran within the last 48 hours\*\*.
* A platelet count less than 50,000 per microliter (µL or mm3)
* Known sensitivity to nicardipine.
* Pre-morbid disability requiring assistance in ambulation or activities of daily living.
* Subject's living will precludes aggressive ICU management.
* Subject is currently participating in another interventional clinical trial

  * Use of dabigatran was clarified through investigator presentations, educational materials, and clinical tools to include newer similar class medications (such as rivaroxaban, apixaban, and edoxaban) that were being developed and in various stages of approval across enrolling countries through the course of this trial, in the event that patients using these medications may have been encountered during screening.

Primary outcomes:
measure: Death or Disability According to Modified Rankin Scale Score at 90 Days (3 Months) From Randomization
timeFrame: 90 days (± 14 days per protocol window; up to ± 30 days data is used) from randomization
Secondary outcomes:
measure: Quality of Life at 90 Days Using EuroQol (EQ) Measures: EQ-5D (EuroQol Five Dimension), Consisting of Standardized EQ-5D-3L (EuroQol Five Dimension, Three-Level) Questionnaire and EQ VAS (EuroQol Visual Analog Scale) Scores
timeFrame: 90 days (± 14 days per protocol window; up to ± 30 days data is used) from randomization
measure: Hematoma Expansion (Number of Patients With Hematoma Expansion of 33% or Greater Between the Baseline and 24 +/- 6 Hours Head CTs, as Measured by the Central Reader for Patients With Readable Scans for Both Time Points Submitted by Data Lock.)
timeFrame: From the baseline head CT to the 24 +/- 6 hours from randomization head CT
Other outcomes:
measure: Neurological Deterioration Within 24 Hours, Defined by a Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score From Baseline, Not Related to Sedation or Hypnotic-agent Use and Sustained for at Least 8 Hours.
timeFrame: From randomization through the 24-hour treatment period
measure: Hypotension Within 72 Hours
timeFrame: From randomization through 72 hours from randomization
measure: Treatment-related Serious Adverse Event Within 72 Hours of Randomization
timeFrame: From randomization through 72 hours (3 days)
measure: Any Serious Adverse Event Within the 90-day Study Period
timeFrame: From randomization through the 90 day visit (90 ± 14 days per protocol window; up to ± 30 days data is used) or until known death, withdrawal, or loss to follow-up.
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Stroke Center
state: Alabama
city: Phoenix
country: United States
facility: Maricopa Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Pheonix
state: Arizona
city: Tuscon
country: United States
facility: Banner University Medical Center - South Campus
state: Arizona
city: Tuscon
country: United States
facility: Banner University Medical Center - University Campus
state: Arizona
city: Fresno
country: United States
facility: Community Regional Medical Center of Fresno
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Regan UCLA Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: San Jose
country: United States
facility: Good Samaritan Hospital
state: California
city: Santa Clara
country: United States
facility: Santa Clara Valley Medical Center
state: California
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: New Haven
country: United States
facility: Yale - New Haven Hospital
state: Connecticut
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Gainesville
country: United States
facility: University of Florida Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tampa
country: United States
facility: University of South Florida, Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Idaho Falls
country: United States
facility: Eastern Idaho Medical Consultants
state: Idaho
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University Memorial Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Lutheran Hospital Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Marrero
country: United States
facility: West Jefferson Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Interim LSU Hospital
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center, Shreveport
state: Louisiana
city: South Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University - Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Sinai-Grace Hospital
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Duluth
country: United States
facility: Essentia Health St. Mary's Medical Center
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: St. Cloud
country: United States
facility: St. Cloud Hospital
state: Minnesota
city: St.Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Neuroscience Institute
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Clifton
country: United States
facility: St. Joseph's Regional Medical Center
state: New Jersey
city: Edison
country: United States
facility: New Jersey Neuroscience Institute, JFK Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Brooklyn
country: United States
facility: New York City Health and Hospitals Corp. / Kings County Hospital
state: New York
city: Brooklyn
country: United States
facility: Mamoides Medical Center
state: New York
city: Buffalo
country: United States
facility: Sister of Charity/Buffalo Mercy Hospital, Catholic Health System
state: New York
city: Johnson City
country: United States
facility: UHS Wilson Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: SUNY Downstate
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Lincoln Medical and Mental Health Center
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Rochester
country: United States
facility: Strong Stroke Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Greenboro
country: United States
facility: Guilford Neurologic Associates
state: North Carolina
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Clinical Research Institute/Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center (Wake Forest School of Medicine)
state: North Carolina
city: Akron
country: United States
facility: Akron General Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University - Wexner Medical Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center (OUHSC)
state: Oklahoma
city: Portland
country: United States
facility: Providence Brain and Spine Institute
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Univ/ Hershey Med Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Mercy Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: York
country: United States
facility: Wellspan York Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Columbia
country: United States
facility: Palmetto Health
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Stroke Center
state: Tennessee
city: Austin
country: United States
facility: Seton Medical Center Austin
state: Texas
city: Austin
country: United States
facility: St. David's Medical Center
state: Texas
city: Austin
country: United States
facility: University Medical Center Brackenridge
state: Texas
city: Dallas
country: United States
facility: UT Southwestern - Parkland Hospital
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
city: Houston
country: United States
facility: Memorial Herman - Texas Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Ben Taub Community Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: Methodist Hospital - The Neurological Institute
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University - Ruby Memorial Hospital
state: West Virginia
city: Milwakee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Shijiazhuang City
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Taiyuan City
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Baotou
country: China
facility: Baotou Central Hospital
city: Beijing
country: China
facility: Beijing Tiantan Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Datong
country: China
facility: Datong Third People's Hospital
city: Taiyuan City
country: China
facility: The First Hospital of Shanxi Medical University
city: Taizhou City
country: China
facility: The First People's Hospital of Taizhou
city: Tianjin
country: China
facility: Tianjin Fourth Central Hospital
city: Wuhan
country: China
facility: Wuhan Brain Hospital
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Zhengzhou
country: China
facility: People's Hopital of Zhengzhou
city: Berlin
country: Germany
facility: Charité Universtity Medicine Berlin
city: Bonn
country: Germany
facility: University of Bonn
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Frankfurt
country: Germany
facility: Clinic Frankfurt Hoechst
city: Halle (Saale)
country: Germany
facility: University Hospital Halle
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Munster
country: Germany
facility: University Hospital Meunster
city: Tubingen
country: Germany
facility: University of Tubingen
city: Nagoya City
country: Japan
facility: Nagoya Medical Center
state: Aichi
city: Sapporo
country: Japan
facility: Nakamura Memorial Hospital
state: Hokkaido
city: Kanagawa
country: Japan
facility: Saiseikai Yokohamashi Tobu Hospital
state: Kanagowa
city: Kumamoto City
country: Japan
facility: Saiseikai Kumamoto Hospital
state: Kumamoto
city: Fukuoka
country: Japan
facility: Kyushu Medical Center
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Kawasaki
country: Japan
facility: St. Marianna - Toyoko
city: Kawasaki
country: Japan
facility: St. Marianna University Hospital
city: Kobe City
country: Japan
facility: Kobe City Medical Center General Hospital
city: Okayama
country: Japan
facility: Kawasaki Medical School
city: Osaka
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Sendai
country: Japan
facility: Kohnan Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Tokyo
country: Japan
facility: Saiseikai Central Hospital - Tokyo
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: Kyorin University
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Hospital
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hopital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Shin-Kong Wu Ho-Su Memorial Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veteran's Hospital
Study officials:
affiliation: University of Minnesota
name: Adnan I Qureshi, MD
role: STUDY_CHAIR
affiliation: Medical University of South Carolina
name: Yuko Y Palesch, PhD
role: STUDY_DIRECTOR
affiliation: University of Minnesota
name: Adnan I Qureshi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Yuko Y Palesch, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
citation: Qureshi AI, Palesch YY, Martin R, Toyoda K, Yamamoto H, Wang Y, Wang Y, Hsu CY, Yoon BW, Steiner T, Butcher K, Hanley DF, Suarez JI. Interpretation and Implementation of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT II). J Vasc Interv Neurol. 2014 Jun;7(2):34-40. No abstract available.
citation: Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, Toyoda K, Wang Y, Yamamoto H, Yoon BW; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43. doi: 10.1056/NEJMoa1603460. Epub 2016 Jun 8.
citation: Qureshi AI, Huang W, Hanley DF, Hsu CY, Martin RH, Malhotra K, Steiner T, Suarez JI, Yamamoto H, Toyoda K. Early Hyperchloremia is Independently Associated with Death or Disability in Patients with Intracerebral Hemorrhage. Neurocrit Care. 2022 Oct;37(2):487-496. doi: 10.1007/s12028-022-01514-2. Epub 2022 May 5.
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