Antihypertensive Treatment of Acute Cerebral Hemorrhage-II (ATACH-II)

• ClinicalTrials.gov Identifier: NCT01176565
• Recruitment Status: Terminated
• First Posted: August 6, 2010
• Results First Posted: April 25, 2017
• Last Update Posted: April 25, 2017
• Sponsor: University of Minnesota
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Medical University of South Carolina; Johns Hopkins University; University of Michigan; Neurocritical Care Research Network; National Cerebral and Cardiovascular Center; Japan Cardiovascular Research Foundation; Beijing Tiantan Hospital; China Medical University Hospital; University Hospital Heidelberg; Seoul National University Hospital
• Information provided by (Responsible Party): University of Minnesota

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Intracerebral Hemorrhage	Drug: Intravenous nicardipine hydrochloride	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: The trial intervention is conducted open-label to avoid concealing clinically necessary patient blood pressure and intravenous drug administration information. Clinical data including SBP values are primarily taken from entries recorded in to the patient's official medical record by hospital staff and are independently monitor-verified. Assessors for the primary outcome (mRS) at 90 days are are unaware of the treatment assignment or in-hospital clinical course of the subjects assessed. De-identified imaging studies are coded independently of subject number so the central imaging reader is unaware of the treatment assignment, clinical findings, or time points of image acquisition for data recorded from imaging. The study (lead) principal investigator and leadership committee members are unable to associate the treatment assignment of subjects to their outcomes or adverse events for purposes of trial decision-making. Adverse events are adjudicated by an independent oversight committee.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 15, 2011
• Actual Primary Completion Date: December 21, 2015
• Actual Study Completion Date: March 8, 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard SBP Reduction Arm; Intravenous nicardipine hydrochloride will be used as necessary (pro re nata or "PRN") as the primary agent in lowering SBP. The goal for the standard BP reduction group will be to reduce and maintain SBP < 180 mmHg for 24 hours from randomization. 160 mmHg is the target SBP for this arm. For the standard group, SBP below the assigned treatment range is not artificially elevated to stay within the range if lower SBP occurs with nicardipine turned off (no fluid bolus given unless SBP falls below 110 mmHg with nicardipine off and there is risk for hypotension). Euvolemic fluid maintenance is encouraged for all patients according to their medical needs, which may differ.	Drug: Intravenous nicardipine hydrochloride; IV nicardipine is initiated at a rate of 5 mg/hr, is continued, and is increased by 2.5 mg/hr increments every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is above the target SBP despite infusion of the maximum nicardipine dose for 30 minutes, a second agent may be used (Labetalol 5-20 mg IV bolus every 15 min; diltiazem/urapidil in countries without labetalol) for another hour. Nicardipine infusion is decreased incrementally or is stopped if SBP falls below the desired treatment range. Fluid bolus for SBP still falling below 110 mmHG (millimeters of mercury) with nicardipine off is given to prevent organ hypoperfusion. Vasopressor agents are not used unless symptoms related to or possibly exacerbated by hypoperfusion are present.; Other Names: Cardene® I.V.; Nicardipine HCl injection; nicardipine hydrochloride injection; nicardipine IV; nicardipine; nicardipine hydrochloride
Active Comparator: Intensive SBP Reduction Arm; Intravenous nicardipine hydrochloride will be used as necessary (pro re nata or "PRN") as the primary agent in lowering SBP. The goal for the intensive BP reduction group will be to reduce and maintain SBP < 140 mmHg for 24 hours from randomization. 125 mmHg is the target SBP for this arm. For the intensive group, SBP falling below 110 mmHg (lower limit of the assigned treatment range) with nicardipine off is treated with normal saline fluid bolus to prevent or remedy hypotension. Euvolemic fluid maintenance is encouraged for all patients according to their medical needs, which may differ.	Drug: Intravenous nicardipine hydrochloride; IV nicardipine is initiated at a rate of 5 mg/hr, is continued, and is increased by 2.5 mg/hr increments every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is above the target SBP despite infusion of the maximum nicardipine dose for 30 minutes, a second agent may be used (Labetalol 5-20 mg IV bolus every 15 min; diltiazem/urapidil in countries without labetalol) for another hour. Nicardipine infusion is decreased incrementally or is stopped if SBP falls below the desired treatment range. Fluid bolus for SBP still falling below 110 mmHG (millimeters of mercury) with nicardipine off is given to prevent organ hypoperfusion. Vasopressor agents are not used unless symptoms related to or possibly exacerbated by hypoperfusion are present.; Other Names: Cardene® I.V.; Nicardipine HCl injection; nicardipine hydrochloride injection; nicardipine IV; nicardipine; nicardipine hydrochloride

Outcome Measures

Primary Outcome Measures :

1. Death or Disability According to Modified Rankin Scale Score at 90 Days (3 Months) From Randomization [ Time Frame: 90 days (± 14 days per protocol window; up to ± 30 days data is used) from randomization ]
   The primary outcome was death or disability, defined by modified Rankin scale (mRS) of 4-6 at 90 days following treatment. The modified Rankin Scale score ranges from 0, indicating no symptoms, to 6, indicating death. A score of 4 indicates moderately severe disability including the inability to walk or attend to one's own bodily needs. A score of 5 indicates severe disability; bedridden, incontinent, and requiring constant nursing care. To score a 3 or lower on the mRS, a person must at least be able to walk without the assistance of another person. We chose the mRS because of its high inter-observer reliability, superiority to other indices, and consistency with previous trials in patients with ICH. Reliability was further increased by use of a structured interview template and by requiring mRS assessors to pass a certification test. Persons conducting the 90-day mRS assessment were to be unaware of the treatment arm or clinical course of the patients they assessed.

Secondary Outcome Measures :

1. 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 [ Time Frame: 90 days (± 14 days per protocol window; up to ± 30 days data is used) from randomization ]
   Standardized scales developed by the EuroQol Research Foundation were used as a secondary outcome measure in addition to the mRS scale score. The EQ-5D is a simple, standardized non-disease-specific instrument for describing and valuating health-related quality of life. The EQ-5D-3L questionnaire consists of 5 questions in 5 different domains and allows for responses from 1 (the best outcome) to 3 (the worst outcome) in each of five categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Total scores range from 5 to 15, with lower scores indicating better quality of life and a higher score indicating a worse quality of life. A second component of EuroQol outcome measurements is a printed 20 cm visual analogue scale (EQ VAS) that appears somewhat like a thermometer, on which a score from 0 (worst imaginable health state or death) to 100 (best imaginable health state) is marked by the patient (or, when necessary, their proxy) with the scale in view.
2. 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.) [ Time Frame: From the baseline head CT to the 24 +/- 6 hours from randomization head CT ]
   Hematoma expansion as determined by serial CT scans: Hematoma expansion was defined as an increase in the volume of intraparenchymal hemorrhage of 33% or greater as measured by a central imaging analyst who was was unaware of the treatment assignments, clinical findings, and time points of image acquisition. The area of the hematoma was delineated by image analysis software with the use of density thresholds on each slice, followed by manual correction. To ensure accuracy and consistency of the readings, images were coded randomly and independently of subject numbers and manual correction was also done without awareness of treatment assignments, clinical findings, or time points of image acquisition. This data point is defined as being present (hematoma expansion of 33% or more was calculated between the baseline scan hematoma volume and the 24 +/- 6 hours hematoma volume measures at data analysis), meaning that hematoma expansion as defined must have occurred or it was not counted.

Other Outcome Measures:

1. 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. [ Time Frame: From randomization through the 24-hour treatment period ]
   Neurologic deterioration was measured using two scales. The Glasgow Coma Scale (GCS) score measures of 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 movement, visual fields, facial palsy, movement in each limb, sensation, language & speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42, with 0 indicating normal function and higher scores indicating greater deficit severity. Neurological status was checked per ICU standards through 24 hours, recommended as hourly GCS and full assessment every 2 hours. NIHSS assessment at baseline and 24 +/- 3 hours was pre-specified. Assessments were added for suspected neurological change.
2. Hypotension Within 72 Hours [ Time Frame: From randomization through 72 hours from randomization ]
   Hypotension (abnormally low blood pressure) was the most likely adverse event that could be associated with the study treatment, and is the primary basis (risk) on which neurological deterioration or other untoward effects of the study treatment could occur. It is therefore examined as a numerically-measured occurrence in addition to monitoring patients closely for neurological deterioration or other symptoms. Hypotension, when named as an adverse event, was defined as the syndrome of low blood pressure with SBP < 85 mmHg. Instances of hypotension were to be avoided through close monitoring, and administration of fluid bolus for SBP < 110 mmHg. If hypotension did occur, it was to be reversed as quickly as possible through discontinuation of intravenous nicardipine and intravenous fluid administration, which can be accomplished readily in a variety of settings where patients with intracerebral hemorrhage are routinely housed during early hospitalization.
3. Treatment-related Serious Adverse Event Within 72 Hours of Randomization [ Time Frame: From randomization through 72 hours (3 days) ]
   Adverse events (AEs) and serious adverse events (SAEs) were assessed by the site investigators for all patients, including for their potential relatedness to the study treatment. An Independent Oversight Committee (IOC) reviewed and adjudicated all adverse event data. The 72-hours-from-randomization time window was considered the most likely time frame during which treatment-related adverse events or serious adverse events would be observed. Terminology from the Medical Dictionary for Regulatory Activities (MedDRA) and severity criteria from the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03) were used as a basis for reporting adverse events. Serious adverse events are defined as being fatal, life-threatening, resulting in hospitalization or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage and were required to be reported promptly.
4. Any Serious Adverse Event Within the 90-day Study Period [ Time Frame: 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. ]
   The complete count of all subjects who experienced any serious adverse events throughout their participation in the trial was included in this tabulation. Adverse events (AEs) and serious adverse events (SAEs) were assessed by the site investigators for all patients. Potential relatedness to the study treatment was a required reporting element for all adverse events but was not considered in this count. Terminology from the Medical Dictionary for Regulatory Activities (MedDRA) and severity criteria from the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03) were used as a basis for reporting adverse events. Serious adverse events are defined as being fatal, life-threatening, resulting in hospitalization or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage and were required to be reported promptly. An Independent Oversight Committee (IOC) reviewed and adjudicated adverse event data.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

UAB Comprehensive Stroke Center

Birmingham, Alabama, United States, 35249

United States, Arizona

Maricopa Medical Center

Phoenix, Arizona, United States, 85008

Mayo Clinic Pheonix

Scottsdale, Arizona, United States, 85259

Banner University Medical Center - South Campus

Tuscon, Arizona, United States, 85713

Banner University Medical Center - University Campus

Tuscon, Arizona, United States, 85724

United States, California

Community Regional Medical Center of Fresno

Fresno, California, United States, 93721

University of California San Diego

La Jolla, California, United States, 92093

Long Beach Memorial Medical Center

Long Beach, California, United States, 90806

Ronald Regan UCLA Medical Center

Los Angeles, California, United States, 90095-9574

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92658

Stanford University

Palo Alto, California, United States, 94304

Sutter Roseville Medical Center

Roseville, California, United States, 95661

UC Davis Medical Center

Sacramento, California, United States, 95817

UCSF Medical Center

San Francisco, California, United States, 94143

Good Samaritan Hospital

San Jose, California, United States, 95124

Santa Clara Valley Medical Center

Santa Clara, California, United States, 95138

United States, Colorado

Colorado Neurological Institute

Englewood, Colorado, United States, 80113

United States, Connecticut

Yale - New Haven Hospital

New Haven, Connecticut, United States, 06510

United States, Delaware

Christiana Hospital

Newark, Delaware, United States, 19718

United States, Florida

University of Florida Gainesville

Gainesville, Florida, United States, 32611

Baptist Medical Center Jacksonville

Jacksonville, Florida, United States, 32207

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States, 32224

University of South Florida, Tampa General Hospital

Tampa, Florida, United States, 33612

United States, Georgia

Grady Memorial Hospital

Atlanta, Georgia, United States, 30303

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

Emory University Hospital

Atlanta, Georgia, United States, 30322

United States, Idaho

Eastern Idaho Medical Consultants

Idaho Falls, Idaho, United States, 83404

United States, Illinois

Loyola University Medical Center

Maywood, Illinois, United States, 60153

Advocate Christ Medical Center

Oak Lawn, Illinois, United States, 60453

OSF Saint Francis Medical Center

Peoria, Illinois, United States, 61637

Southern Illinois University Memorial Medical Center

Springfield, Illinois, United States, 62794-9643

United States, Indiana

Lutheran Hospital Indiana

Fort Wayne, Indiana, United States, 46804

Parkview Hospital

Fort Wayne, Indiana, United States, 46805

United States, Kansas

Kansas University Medical Center

Kansas City, Kansas, United States, 66160

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536-0296

University of Louisville

Louisville, Kentucky, United States, 40292

United States, Louisiana

West Jefferson Medical Center

Marrero, Louisiana, United States, 70072

Interim LSU Hospital

New Orleans, Louisiana, United States, 70112

Tulane Medical Center

New Orleans, Louisiana, United States, 70112

Ochsner Clinic Foundation

New Orleans, Louisiana, United States, 70121

Louisiana State University Health Sciences Center, Shreveport

Shreveport, Louisiana, United States, 71103

United States, Maine

Maine Medical Center

South Portland, Maine, United States, 04106

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Brigham & Women's Hospital

Boston, Massachusetts, United States, 02115

Boston Medical Center

Boston, Massachusetts, United States, 02118

United States, Michigan

Wayne State University - Detroit Receiving Hospital

Detroit, Michigan, United States, 48201

Henry Ford Health System

Detroit, Michigan, United States, 48202

Sinai-Grace Hospital

Detroit, Michigan, United States, 48235

Allegiance Health

Jackson, Michigan, United States, 49201

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Essentia Health St. Mary's Medical Center

Duluth, Minnesota, United States, 55805

Fairview Southdale Hospital

Edina, Minnesota, United States, 55435

Hennepin County Medical Center

Minneapolis, Minnesota, United States, 55404

St. Cloud Hospital

St. Cloud, Minnesota, United States, 56303

Regions Hospital

St.Paul, Minnesota, United States, 55101

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Missouri

Saint Luke's Neuroscience Institute

Kansas City, Missouri, United States, 64111

Research Medical Center

Kansas City, Missouri, United States, 64132

Saint Louis University

Saint Louis, Missouri, United States, 63104

United States, New Jersey

Cooper University Hospital

Camden, New Jersey, United States, 08103

St. Joseph's Regional Medical Center

Clifton, New Jersey, United States, 07012

New Jersey Neuroscience Institute, JFK Medical Center

Edison, New Jersey, United States, 08818

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87131

United States, New York

New York City Health and Hospitals Corp. / Kings County Hospital

Brooklyn, New York, United States, 11203

Mamoides Medical Center

Brooklyn, New York, United States, 11219

Sister of Charity/Buffalo Mercy Hospital, Catholic Health System

Buffalo, New York, United States, 14214

UHS Wilson Medical Center

Johnson City, New York, United States, 13790

North Shore University Hospital

Manhasset, New York, United States, 11030

SUNY Downstate

New York, New York, United States, 10029

Columbia University

New York, New York, United States, 10032

Lincoln Medical and Mental Health Center

New York, New York, United States, 10451

Rochester General Hospital

Rochester, New York, United States, 14621

Strong Stroke Center

Rochester, New York, United States, 14642

United States, North Carolina

Mission Hospital

Asheville, North Carolina, United States, 28801-4601

Guilford Neurologic Associates

Greenboro, North Carolina, United States, 27405

Vidant Medical Center

Greenville, North Carolina, United States, 27834

Novant Clinical Research Institute/Forsyth Medical Center

Winston-Salem, North Carolina, United States, 27103

Wake Forest Baptist Medical Center (Wake Forest School of Medicine)

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Akron General Hospital

Akron, Ohio, United States, 44307

University Hospitals Case Medical Center

Cleveland, Ohio, United States, 44106

Ohio State University - Wexner Medical Center

Columbus, Ohio, United States, 43210

University of Toledo Medical Center

Toledo, Ohio, United States, 43614

United States, Oklahoma

Oklahoma University Health Sciences Center (OUHSC)

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Providence Brain and Spine Institute

Portland, Oregon, United States, 97225

United States, Pennsylvania

Abington Memorial Hospital

Abington, Pennsylvania, United States, 19001

Lehigh Valley Health Network

Allentown, Pennsylvania, United States, 18103

Geisinger Medical Center

Danville, Pennsylvania, United States, 17822

Penn State Univ/ Hershey Med Center

Hershey, Pennsylvania, United States, 17033

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States, 19102

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Temple University

Philadelphia, Pennsylvania, United States, 19140

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States, 15213

UPMC-Mercy Hospital

Pittsburgh, Pennsylvania, United States, 15219

Reading Hospital

West Reading, Pennsylvania, United States, 19611

Wellspan York Hospital

York, Pennsylvania, United States, 17403

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

Palmetto Health

Columbia, South Carolina, United States, 29203

United States, Tennessee

Vanderbilt Stroke Center

Nashville, Tennessee, United States, 37232

United States, Texas

Seton Medical Center Austin

Austin, Texas, United States, 78705

St. David's Medical Center

Austin, Texas, United States, 78705

University Medical Center Brackenridge

Austin, Texas, United States, 78705

UT Southwestern - Parkland Hospital

Dallas, Texas, United States, 75235

Texas Tech University Health Sciences Center

El Paso, Texas, United States, 79430

Valley Baptist Medical Center

Harlingen, Texas, United States, 78550

Memorial Herman - Texas Medical Center

Houston, Texas, United States, 77024

Baylor College of Medicine - Ben Taub Community Hospital

Houston, Texas, United States, 77030

Baylor College of Medicine - St. Luke's Episcopal Hospital

Houston, Texas, United States, 77030

Methodist Hospital - The Neurological Institute

Houston, Texas, United States, 77030

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

United States, Utah

Intermountain Medical Center

Murray, Utah, United States, 84107

United States, Virginia

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States, 23298-0631

United States, West Virginia

West Virginia University - Ruby Memorial Hospital

Morgantown, West Virginia, United States, 26506

United States, Wisconsin

Medical College of Wisconsin

Milwakee, Wisconsin, United States, 53226

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States, 53215

Canada, Alberta

University of Alberta

Edmonton, Alberta, Canada, 2E3.27WMC

Canada, Quebec

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada, H3A 2B4

China, Hebei

The Second Hospital of Hebei Medical University

Shijiazhuang City, Hebei, China, 050000

China, Shanxi

The Second Hospital of Shanxi Medical University

Taiyuan City, Shanxi, China, 030001

China

Baotou Central Hospital

Baotou, China

Beijing Tiantan Hospital

Beijing, China, 100050

Peking University Third Hospital

Beijing, China, 100191

Datong Third People's Hospital

Datong, China

The First Hospital of Shanxi Medical University

Taiyuan City, China, 030001

The First People's Hospital of Taizhou

Taizhou City, China, 318020

Tianjin Fourth Central Hospital

Tianjin, China, 300140

Wuhan Brain Hospital

Wuhan, China, 430019

Renmin Hospital of Wuhan University

Wuhan, China, 430060

People's Hopital of Zhengzhou

Zhengzhou, China, 450003

Germany

Charité Universtity Medicine Berlin

Berlin, Germany, 12203

University of Bonn

Bonn, Germany, 53105

University Hospital Dresden

Dresden, Germany, 01307

Clinic Frankfurt Hoechst

Frankfurt, Germany, 65929

University Hospital Halle

Halle (Saale), Germany, 06120

University Hospital Heidelberg

Heidelberg, Germany, 69120

University Hospital Leipzig

Leipzig, Germany, 04103

University Hospital Mannheim

Mannheim, Germany, 68167

University Hospital Meunster

Munster, Germany, 48129

University of Tubingen

Tubingen, Germany, 72076

Japan

Nagoya Medical Center

Nagoya City, Aichi, Japan, 460-0001

Nakamura Memorial Hospital

Sapporo, Hokkaido, Japan, 060-8570

Saiseikai Yokohamashi Tobu Hospital

Kanagawa, Kanagowa, Japan, 230-8765

Saiseikai Kumamoto Hospital

Kumamoto City, Kumamoto, Japan, 861-4193

Kyushu Medical Center

Fukuoka, Japan, 810-8563

Gifu University Hospital

Gifu, Japan, 501-1194

St. Marianna - Toyoko

Kawasaki, Japan, 211-0063

St. Marianna University Hospital

Kawasaki, Japan, 216-8511

Kobe City Medical Center General Hospital

Kobe City, Japan

Kawasaki Medical School

Okayama, Japan, 701-0192

National Cerebral and Cardiovascular Center

Osaka, Japan, 565-8565

Kohnan Hospital

Sendai, Japan

Toranomon Hospital

Tokyo, Japan, 105-8470

Saiseikai Central Hospital - Tokyo

Tokyo, Japan, 108-0073

Keio University Hospital

Tokyo, Japan, 160-8582

Kyorin University

Tokyo, Japan

Korea, Republic of

Seoul National University Bundang Hospital

Seongnam, Gyeonggi, Korea, Republic of

Chonnam National University Hospital

Gwangju, Korea, Republic of, 501-757

Seoul National University Hospital

Seoul, Korea, Republic of, 110-744

Kyung Hee University Hospital

Seoul, Korea, Republic of, 130-702

Seoul National University Boramae Hospital

Seoul, Korea, Republic of, 156-707

Taiwan

Changhua Christian Hospital

Changhua, Taiwan

Kaohsiung Veterans General Hospital

Kaohsiung City, Taiwan

Kaohsiung Medical University Hospital

Kaohsiung, Taiwan, 807

Taichung Veterans General Hopital

Taichung City, Taiwan, 407

China Medical University Hospital

Taichung, Taiwan, 404

National Cheng Kung University Hospital

Tainan, Taiwan

National Taiwan University Hospital

Taipei, Taiwan, 100

Shin-Kong Wu Ho-Su Memorial Hospital

Taipei, Taiwan, 111

Tri-Service General Hospital

Taipei, Taiwan, 114

Taipei Veteran's Hospital

Taipei, Taiwan

Sponsors and Collaborators

University of Minnesota

National Institute of Neurological Disorders and Stroke (NINDS)

Medical University of South Carolina

Johns Hopkins University

University of Michigan

Neurocritical Care Research Network

National Cerebral and Cardiovascular Center

Japan Cardiovascular Research Foundation

Beijing Tiantan Hospital

China Medical University Hospital

University Hospital Heidelberg

Seoul National University Hospital

Investigators

• Study Chair: Adnan I Qureshi, MD; University of Minnesota
• Study Director: Yuko Y Palesch, PhD; Medical University of South Carolina
• Principal Investigator: Adnan I Qureshi, MD; University of Minnesota
• Principal Investigator: Yuko Y Palesch, PhD; Medical University of South Carolina

More Information

Additional Information:

Study protocol 

Study Data/Documents: Study Protocol 

Identifier: Protocol

Publications of Results:

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.

Other Publications:

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.

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.

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.

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.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Tanaka K, Koga M, Fukuda-Doi M, Qureshi AI, Yamamoto H, Miwa K, Ihara M, Toyoda K; ATACH-2 Trial Investigators. Temporal Trajectory of Systolic Blood Pressure and Outcomes in Acute Intracerebral Hemorrhage: ATACH-2 Trial Cohort. Stroke. 2022 Jun;53(6):1854-1862. doi: 10.1161/STROKEAHA.121.037186. Epub 2022 Apr 11.

Tsukita K, Sakamaki-Tsukita H, Takahashi R. Long-term Effect of Regular Physical Activity and Exercise Habits in Patients With Early Parkinson Disease. Neurology. 2022 Feb 22;98(8):e859-e871. doi: 10.1212/WNL.0000000000013218. Epub 2022 Jan 12.

Magid-Bernstein JR, Li Y, Cho SM, Piran PJ, Roh DJ, Gupta A, Shoamanesh A, Merkler A, Zhang C, Avadhani R, Montano N, Iadecola C, Falcone GJ, Sheth KN, Qureshi AI, Rosand J, Goldstein J, Awad I, Hanley DF, Kamel H, Ziai WC, Murthy SB. Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials. Neurology. 2022 Mar 8;98(10):e1013-e1020. doi: 10.1212/WNL.0000000000013247. Epub 2021 Dec 22.

Qureshi AI, Huang W, Lobanova I, Chandrasekaran PN, Hanley DF, Hsu CY, Martin RH, Steiner T, Suarez JI, Yamamoto H, Toyoda K. Effect of Moderate and Severe Persistent Hyperglycemia on Outcomes in Patients With Intracerebral Hemorrhage. Stroke. 2022 Apr;53(4):1226-1234. doi: 10.1161/STROKEAHA.121.034928. Epub 2021 Nov 30.

Miwa K, Koga M, Fukuda-Doi M, Yamamoto H, Tanaka K, Yoshimura S, Ihara M, Qureshi AI, Toyoda K. Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH-2. J Am Heart Assoc. 2021 Aug 17;10(16):e020364. doi: 10.1161/JAHA.120.020364. Epub 2021 Aug 13.

Shoamanesh A, Cassarly C, Morotti A, Romero JM, Oliveira-Filho J, Schlunk F, Jessel M, Butcher K, Gioia L, Ayres A, Vashkevich A, Schwab K, Afzal MR, Martin RH, Qureshi AI, Greenberg SM, Rosand J, Goldstein JN; ATACH-2 and NETT investigators. Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial. Neurocrit Care. 2022 Feb;36(1):71-81. doi: 10.1007/s12028-021-01254-9. Epub 2021 Jul 22.

Fukuda-Doi M, Yamamoto H, Koga M, Doi Y, Qureshi AI, Yoshimura S, Miwa K, Ishigami A, Shiozawa M, Omae K, Ihara M, Toyoda K. Impact of Renal Impairment on Intensive Blood-Pressure-Lowering Therapy and Outcomes in Intracerebral Hemorrhage: Results From ATACH-2. Neurology. 2021 Aug 31;97(9):e913-e921. doi: 10.1212/WNL.0000000000012442. Epub 2021 Jul 1.

Yogendrakumar V, Ramsay T, Menon BK, Qureshi AI, Saver JL, Dowlatshahi D. Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments. Neurology. 2021 Aug 24;97(8):e755-e764. doi: 10.1212/WNL.0000000000012393. Epub 2021 Jun 18.

Toyoda K, Palesch YY, Koga M, Foster L, Yamamoto H, Yoshimura S, Ihara M, Fukuda-Doi M, Okazaki S, Tanaka K, Miwa K, Hasegawa Y, Shiokawa Y, Iwama T, Kamiyama K, Hoshino H, Steiner T, Yoon BW, Wang Y, Hsu CY, Qureshi AI; ATACH-2 Trial Investigators. Regional Differences in the Response to Acute Blood Pressure Lowering After Cerebral Hemorrhage. Neurology. 2021 Feb 2;96(5):e740-e751. doi: 10.1212/WNL.0000000000011229. Epub 2020 Nov 20.

Qureshi AI, Huang W, Lobanova I, Hanley DF, Hsu CY, Malhotra K, Steiner T, Suarez JI, Toyoda K, Yamamoto H; Antihypertensive Treatment of Cerebral Hemorrhage 2 Trial Investigators. Systolic Blood Pressure Reduction and Acute Kidney Injury in Intracerebral Hemorrhage. Stroke. 2020 Oct;51(10):3030-3038. doi: 10.1161/STROKEAHA.120.030272. Epub 2020 Aug 25.

Fukuda-Doi M, Yamamoto H, Koga M, Palesch YY, Durkalski-Mauldin VL, Qureshi AI, Yoshimura S, Okazaki S, Miwa K, Okada Y, Ueda T, Okuda S, Nakahara J, Suzuki N, Toyoda K. Sex Differences in Blood Pressure-Lowering Therapy and Outcomes Following Intracerebral Hemorrhage: Results From ATACH-2. Stroke. 2020 Aug;51(8):2282-2286. doi: 10.1161/STROKEAHA.120.029770. Epub 2020 Jul 6.

Qureshi AI, Foster LD, Lobanova I, Huang W, Suarez JI. Intensive Blood Pressure Lowering in Patients with Moderate to Severe Grade Acute Cerebral Hemorrhage: Post Hoc Analysis of Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 Trial. Cerebrovasc Dis. 2020;49(3):244-252. doi: 10.1159/000506358. Epub 2020 Jun 25.

Toyoda K, Koga M, Yamamoto H, Foster L, Palesch YY, Wang Y, Sakai N, Hara T, Hsu CY, Itabashi R, Sato S, Fukuda-Doi M, Steiner T, Yoon BW, Hanley DF, Qureshi AI; ATACH-2 Trial Investigators. Clinical Outcomes Depending on Acute Blood Pressure After Cerebral Hemorrhage. Ann Neurol. 2019 Jan;85(1):105-113. doi: 10.1002/ana.25379. Epub 2019 Jan 7.

Moullaali TJ, Wang X, Martin RH, Shipes VB, Qureshi AI, Anderson CS, Palesch YY. Statistical analysis plan for pooled individual patient data from two landmark randomized trials (INTERACT2 and ATACH-II) of intensive blood pressure lowering treatment in acute intracerebral hemorrhage. Int J Stroke. 2019 Apr;14(3):321-328. doi: 10.1177/1747493018813695. Epub 2018 Nov 12.

Qureshi AI, Palesch YY, Foster LD, Barsan WG, Goldstein JN, Hanley DF, Hsu CY, Moy CS, Qureshi MH, Silbergleit R, Suarez JI, Toyoda K, Yamamoto H; ATACH 2 Trial Investigators. Blood Pressure-Attained Analysis of ATACH 2 Trial. Stroke. 2018 Jun;49(6):1412-1418. doi: 10.1161/STROKEAHA.117.019845. Epub 2018 May 22.

Shoamanesh A, Morotti A, Romero JM, Oliveira-Filho J, Schlunk F, Jessel MJ, Ayres AM, Vashkevich A, Schwab K, Afzal MR, Cassarly C, Martin RH, Qureshi AI, Greenberg SM, Rosand J, Goldstein JN; Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) and the Neurological Emergencies Treatment Trials (NETT) Network Investigators. Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial. JAMA Neurol. 2018 Jul 1;75(7):850-859. doi: 10.1001/jamaneurol.2018.0454.

Morotti A, Boulouis G, Romero JM, Brouwers HB, Jessel MJ, Vashkevich A, Schwab K, Afzal MR, Cassarly C, Greenberg SM, Martin RH, Qureshi AI, Rosand J, Goldstein JN; ATACH-II and NETT investigators. Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion. Neurology. 2017 Aug 8;89(6):548-554. doi: 10.1212/WNL.0000000000004210. Epub 2017 Jul 12.

Morotti A, Brouwers HB, Romero JM, Jessel MJ, Vashkevich A, Schwab K, Afzal MR, Cassarly C, Greenberg SM, Martin RH, Qureshi AI, Rosand J, Goldstein JN; Antihypertensive Treatment of Acute Cerebral Hemorrhage II and Neurological Emergencies Treatment Trials Investigators. Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage: A Secondary Analysis of a Randomized Clinical Trial. JAMA Neurol. 2017 Aug 1;74(8):950-960. doi: 10.1001/jamaneurol.2017.1014.

Rodriguez-Luna D, Pineiro S, Rubiera M, Ribo M, Coscojuela P, Pagola J, Flores A, Muchada M, Ibarra B, Meler P, Sanjuan E, Hernandez-Guillamon M, Alvarez-Sabin J, Montaner J, Molina CA. Impact of blood pressure changes and course on hematoma growth in acute intracerebral hemorrhage. Eur J Neurol. 2013 Sep;20(9):1277-83. doi: 10.1111/ene.12180. Epub 2013 May 5.

Toyoda K, Sato S, Koga M, Yamamoto H, Nakagawara J, Furui E, Shiokawa Y, Hasegawa Y, Okuda S, Sakai N, Kimura K, Okada Y, Yoshimura S, Hoshino H, Uesaka Y, Nakashima T, Itoh Y, Ueda T, Nishi T, Gotoh J, Nagatsuka K, Arihiro S, Yamaguchi T, Minematsu K. Run-up to participation in ATACH II in Japan. J Vasc Interv Neurol. 2012 Aug;5(supp):1-5.

Sato S, Yamamoto H, Qureshi AI, Palesch YY, Toyoda K; ATACH-II study group. [Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-II at Japan site: study design and advance construction of domestic research network]. Rinsho Shinkeigaku. 2012;52(9):642-50. doi: 10.5692/clinicalneurol.52.642. Japanese.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01176565
• Other Study ID Numbers: 1207M17921; U01NS062091 ( U.S. NIH Grant/Contract ); U01NS061861 ( U.S. NIH Grant/Contract ); U01NS059041 ( U.S. NIH Grant/Contract ); U01NS056975 ( U.S. NIH Grant/Contract ); H23-4-3 ( Other Grant/Funding Number: Intramural Research Fund for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center, Japan )
• First Posted: August 6, 2010
• Results First Posted: April 25, 2017
• Last Update Posted: April 25, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: A public use data set from the study database will be made available. A process for sharing subject head imaging studies that may be associated with the data set is under evaluation.

Keywords provided by University of Minnesota:

Acute hypertensive response; intracerebral hemorrhage; blood pressure; outcome; nicardipine

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Nicardipine; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents