Antihypertensive Treatment of Acute Cerebral Hemorrhage-II

NCT ID: NCT01176565

Last Updated: 2017-04-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-15

Study Completion Date

2016-03-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Intracerebral Hemorrhage

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type ACTIVE_COMPARATOR

Intravenous nicardipine hydrochloride

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Intravenous nicardipine hydrochloride

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Cardene® I.V. Nicardipine HCl injection nicardipine hydrochloride injection nicardipine IV nicardipine nicardipine hydrochloride

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

Neurocritical Care Research Network

UNKNOWN

Sponsor Role collaborator

National Cerebral and Cardiovascular Center, Japan

OTHER

Sponsor Role collaborator

Japan Cardiovascular Research Foundation

OTHER

Sponsor Role collaborator

Beijing Tiantan Hospital

OTHER

Sponsor Role collaborator

China Medical University Hospital

OTHER

Sponsor Role collaborator

University Hospital Heidelberg

OTHER

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Adnan I Qureshi, MD

Role: STUDY_CHAIR

University of Minnesota

Yuko Y Palesch, PhD

Role: STUDY_DIRECTOR

Medical University of South Carolina

Adnan I Qureshi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Yuko Y Palesch, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UAB Comprehensive Stroke Center

Birmingham, Alabama, United States

Site Status

Maricopa Medical Center

Phoenix, Arizona, United States

Site Status

Mayo Clinic Pheonix

Scottsdale, Arizona, United States

Site Status

Banner University Medical Center - South Campus

Tuscon, Arizona, United States

Site Status

Banner University Medical Center - University Campus

Tuscon, Arizona, United States

Site Status

Community Regional Medical Center of Fresno

Fresno, California, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Ronald Regan UCLA Medical Center

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Sutter Roseville Medical Center

Roseville, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

Good Samaritan Hospital

San Jose, California, United States

Site Status

Santa Clara Valley Medical Center

Santa Clara, California, United States

Site Status

Colorado Neurological Institute

Englewood, Colorado, United States

Site Status

Yale - New Haven Hospital

New Haven, Connecticut, United States

Site Status

Christiana Hospital

Newark, Delaware, United States

Site Status

University of Florida Gainesville

Gainesville, Florida, United States

Site Status

Baptist Medical Center Jacksonville

Jacksonville, Florida, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

University of South Florida, Tampa General Hospital

Tampa, Florida, United States

Site Status

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Eastern Idaho Medical Consultants

Idaho Falls, Idaho, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Southern Illinois University Memorial Medical Center

Springfield, Illinois, United States

Site Status

Lutheran Hospital Indiana

Fort Wayne, Indiana, United States

Site Status

Parkview Hospital

Fort Wayne, Indiana, United States

Site Status

Kansas University Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

West Jefferson Medical Center

Marrero, Louisiana, United States

Site Status

Interim LSU Hospital

New Orleans, Louisiana, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Louisiana State University Health Sciences Center, Shreveport

Shreveport, Louisiana, United States

Site Status

Maine Medical Center

South Portland, Maine, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Wayne State University - Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Sinai-Grace Hospital

Detroit, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

Essentia Health St. Mary's Medical Center

Duluth, Minnesota, United States

Site Status

Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

St. Cloud Hospital

Saint Cloud, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Saint Luke's Neuroscience Institute

Kansas City, Missouri, United States

Site Status

Research Medical Center

Kansas City, Missouri, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

St. Joseph's Regional Medical Center

Clifton, New Jersey, United States

Site Status

New Jersey Neuroscience Institute, JFK Medical Center

Edison, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

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

Brooklyn, New York, United States

Site Status

Mamoides Medical Center

Brooklyn, New York, United States

Site Status

Sister of Charity/Buffalo Mercy Hospital, Catholic Health System

Buffalo, New York, United States

Site Status

UHS Wilson Medical Center

Johnson City, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

SUNY Downstate

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Lincoln Medical and Mental Health Center

New York, New York, United States

Site Status

Rochester General Hospital

Rochester, New York, United States

Site Status

Strong Stroke Center

Rochester, New York, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

Guilford Neurologic Associates

Greenboro, North Carolina, United States

Site Status

Vidant Medical Center

Greenville, North Carolina, United States

Site Status

Novant Clinical Research Institute/Forsyth Medical Center

Winston-Salem, North Carolina, United States

Site Status

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

Winston-Salem, North Carolina, United States

Site Status

Akron General Hospital

Akron, Ohio, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Ohio State University - Wexner Medical Center

Columbus, Ohio, United States

Site Status

University of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Oklahoma University Health Sciences Center (OUHSC)

Oklahoma City, Oklahoma, United States

Site Status

Providence Brain and Spine Institute

Portland, Oregon, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Univ/ Hershey Med Center

Hershey, Pennsylvania, United States

Site Status

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Temple University

Philadelphia, Pennsylvania, United States

Site Status

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC-Mercy Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Reading Hospital

West Reading, Pennsylvania, United States

Site Status

Wellspan York Hospital

York, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Palmetto Health

Columbia, South Carolina, United States

Site Status

Vanderbilt Stroke Center

Nashville, Tennessee, United States

Site Status

Seton Medical Center Austin

Austin, Texas, United States

Site Status

St. David's Medical Center

Austin, Texas, United States

Site Status

University Medical Center Brackenridge

Austin, Texas, United States

Site Status

UT Southwestern - Parkland Hospital

Dallas, Texas, United States

Site Status

Texas Tech University Health Sciences Center

El Paso, Texas, United States

Site Status

Valley Baptist Medical Center

Harlingen, Texas, United States

Site Status

Memorial Herman - Texas Medical Center

Houston, Texas, United States

Site Status

Baylor College of Medicine - Ben Taub Community Hospital

Houston, Texas, United States

Site Status

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

Houston, Texas, United States

Site Status

Methodist Hospital - The Neurological Institute

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Site Status

West Virginia University - Ruby Memorial Hospital

Morgantown, West Virginia, United States

Site Status

Medical College of Wisconsin

Milwakee, Wisconsin, United States

Site Status

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

Site Status

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Site Status

The Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Site Status

Baotou Central Hospital

Baotou, , China

Site Status

Beijing Tiantan Hospital

Beijing, , China

Site Status

Peking University Third Hospital

Beijing, , China

Site Status

Datong Third People's Hospital

Datong, , China

Site Status

The First Hospital of Shanxi Medical University

Taiyuan, , China

Site Status

The First People's Hospital of Taizhou

Taizhou, , China

Site Status

Tianjin Fourth Central Hospital

Tianjin, , China

Site Status

Wuhan Brain Hospital

Wuhan, , China

Site Status

Renmin Hospital of Wuhan University

Wuhan, , China

Site Status

People's Hopital of Zhengzhou

Zhengzhou, , China

Site Status

Charité Universtity Medicine Berlin

Berlin, , Germany

Site Status

University of Bonn

Bonn, , Germany

Site Status

University Hospital Dresden

Dresden, , Germany

Site Status

Clinic Frankfurt Hoechst

Frankfurt, , Germany

Site Status

University Hospital Halle

Halle, , Germany

Site Status

University Hospital Heidelberg

Heidelberg, , Germany

Site Status

University Hospital Leipzig

Leipzig, , Germany

Site Status

University Hospital Mannheim

Mannheim, , Germany

Site Status

University Hospital Meunster

Münster, , Germany

Site Status

University of Tubingen

Tübingen, , Germany

Site Status

Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Site Status

Nakamura Memorial Hospital

Sapporo, Hokkaido, Japan

Site Status

Saiseikai Yokohamashi Tobu Hospital

Kanagawa, Kanagowa, Japan

Site Status

Saiseikai Kumamoto Hospital

Kumamoto, Kumamoto, Japan

Site Status

Kyushu Medical Center

Fukuoka, , Japan

Site Status

Gifu University Hospital

Gifu, , Japan

Site Status

St. Marianna - Toyoko

Kawasaki, , Japan

Site Status

St. Marianna University Hospital

Kawasaki, , Japan

Site Status

Kobe City Medical Center General Hospital

Kobe, , Japan

Site Status

Kawasaki Medical School

Okayama, , Japan

Site Status

National Cerebral and Cardiovascular Center

Osaka, , Japan

Site Status

Kohnan Hospital

Sendai, , Japan

Site Status

Toranomon Hospital

Tokyo, , Japan

Site Status

Saiseikai Central Hospital - Tokyo

Tokyo, , Japan

Site Status

Keio University Hospital

Tokyo, , Japan

Site Status

Kyorin University

Tokyo, , Japan

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Chonnam National University Hospital

Gwangju, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Kyung Hee University Hospital

Seoul, , South Korea

Site Status

Seoul National University Boramae Hospital

Seoul, , South Korea

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hopital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Shin-Kong Wu Ho-Su Memorial Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Taipei Veteran's Hospital

Taipei, , Taiwan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada China Germany Japan South Korea Taiwan

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 20457956 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19770736 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18606927 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17356194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21626077 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22560810 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25132910 (View on PubMed)

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.

Reference Type RESULT
PMID: 27276234 (View on PubMed)

Li Q, Lv X, Morotti A, Qureshi AI, Dowlatshahi D, Falcone GJ, Sheth KN, Shoamanesh A, Murthy SB, Viswanathan A, Goldstein JN. Optimal Magnitude of Blood Pressure Reduction and Hematoma Growth and Functional Outcomes in Intracerebral Hemorrhage. Neurology. 2025 Mar 11;104(5):e213412. doi: 10.1212/WNL.0000000000213412. Epub 2025 Feb 6.

Reference Type DERIVED
PMID: 39913881 (View on PubMed)

Tsukita K, Sakamaki-Tsukita H, Kaiser S, Zhang L, Messa M, Serrano-Fernandez P, Takahashi R. High-Throughput CSF Proteomics and Machine Learning to Identify Proteomic Signatures for Parkinson Disease Development and Progression. Neurology. 2023 Oct 3;101(14):e1434-e1447. doi: 10.1212/WNL.0000000000207725. Epub 2023 Aug 16.

Reference Type DERIVED
PMID: 37586882 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35513751 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35400202 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35022304 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34937780 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34844422 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34387101 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34292474 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34210824 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34144995 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33219136 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32838673 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32623977 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32585668 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30421455 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30418098 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29789395 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29710119 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28701501 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28628707 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23647568 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23230457 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22989898 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

U01NS062091

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01NS061861

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01NS059041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01NS056975

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H23-4-3

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1207M17921

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.