NCT01176565

Brief Summary

The specific aims of this study are to:

  1. 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. 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. 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. 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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,000

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2011

Longer than P75 for phase_3

Geographic Reach
7 countries

171 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 4, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 6, 2010

Completed
9 months until next milestone

Study Start

First participant enrolled

May 15, 2011

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 21, 2015

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 8, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

April 25, 2017

Completed
Last Updated

April 25, 2017

Status Verified

March 1, 2017

Enrollment Period

4.6 years

First QC Date

August 4, 2010

Results QC Date

January 1, 2017

Last Update Submit

March 13, 2017

Conditions

Keywords

Acute hypertensive responseintracerebral hemorrhageblood pressureoutcomenicardipine

Outcome Measures

Primary Outcomes (1)

  • Death or Disability According to Modified Rankin Scale Score at 90 Days (3 Months) 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.

    90 days (± 14 days per protocol window; up to ± 30 days data is used) from randomization

Secondary Outcomes (2)

  • 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

    90 days (± 14 days per protocol window; up to ± 30 days data is used) from randomization

  • 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.)

    From the baseline head CT to the 24 +/- 6 hours from randomization head CT

Other Outcomes (4)

  • 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.

    From randomization through the 24-hour treatment period

  • Hypotension Within 72 Hours

    From randomization through 72 hours from randomization

  • Treatment-related Serious Adverse Event Within 72 Hours of Randomization

    From randomization through 72 hours (3 days)

  • +1 more other outcomes

Study Arms (2)

Standard SBP Reduction Arm

ACTIVE COMPARATOR

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

Intensive SBP Reduction Arm

ACTIVE COMPARATOR

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

Interventions

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.

Also known as: Cardene® I.V., Nicardipine HCl injection, nicardipine hydrochloride injection, nicardipine IV, nicardipine, nicardipine hydrochloride
Intensive SBP Reduction ArmStandard SBP Reduction Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (171)

UAB Comprehensive Stroke Center

Birmingham, Alabama, 35249, United States

Location

Maricopa Medical Center

Phoenix, Arizona, 85008, United States

Location

Mayo Clinic Pheonix

Scottsdale, Arizona, 85259, United States

Location

Banner University Medical Center - South Campus

Tuscon, Arizona, 85713, United States

Location

Banner University Medical Center - University Campus

Tuscon, Arizona, 85724, United States

Location

Community Regional Medical Center of Fresno

Fresno, California, 93721, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Ronald Regan UCLA Medical Center

Los Angeles, California, 90095-9574, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92658, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Sutter Roseville Medical Center

Roseville, California, 95661, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Good Samaritan Hospital

San Jose, California, 95124, United States

Location

Santa Clara Valley Medical Center

Santa Clara, California, 95138, United States

Location

Colorado Neurological Institute

Englewood, Colorado, 80113, United States

Location

Yale - New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Christiana Hospital

Newark, Delaware, 19718, United States

Location

University of Florida Gainesville

Gainesville, Florida, 32611, United States

Location

Baptist Medical Center Jacksonville

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of South Florida, Tampa General Hospital

Tampa, Florida, 33612, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Eastern Idaho Medical Consultants

Idaho Falls, Idaho, 83404, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Southern Illinois University Memorial Medical Center

Springfield, Illinois, 62794-9643, United States

Location

Lutheran Hospital Indiana

Fort Wayne, Indiana, 46804, United States

Location

Parkview Hospital

Fort Wayne, Indiana, 46805, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0296, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

West Jefferson Medical Center

Marrero, Louisiana, 70072, United States

Location

Interim LSU Hospital

New Orleans, Louisiana, 70112, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Louisiana State University Health Sciences Center, Shreveport

Shreveport, Louisiana, 71103, United States

Location

Maine Medical Center

South Portland, Maine, 04106, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Wayne State University - Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Sinai-Grace Hospital

Detroit, Michigan, 48235, United States

Location

Allegiance Health

Jackson, Michigan, 49201, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Essentia Health St. Mary's Medical Center

Duluth, Minnesota, 55805, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55404, United States

Location

St. Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Saint Luke's Neuroscience Institute

Kansas City, Missouri, 64111, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

St. Joseph's Regional Medical Center

Clifton, New Jersey, 07012, United States

Location

New Jersey Neuroscience Institute, JFK Medical Center

Edison, New Jersey, 08818, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

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

Brooklyn, New York, 11203, United States

Location

Mamoides Medical Center

Brooklyn, New York, 11219, United States

Location

Sister of Charity/Buffalo Mercy Hospital, Catholic Health System

Buffalo, New York, 14214, United States

Location

UHS Wilson Medical Center

Johnson City, New York, 13790, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

SUNY Downstate

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Lincoln Medical and Mental Health Center

New York, New York, 10451, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

Strong Stroke Center

Rochester, New York, 14642, United States

Location

Mission Hospital

Asheville, North Carolina, 28801-4601, United States

Location

Guilford Neurologic Associates

Greenboro, North Carolina, 27405, United States

Location

Vidant Medical Center

Greenville, North Carolina, 27834, United States

Location

Novant Clinical Research Institute/Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

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

Winston-Salem, North Carolina, 27157, United States

Location

Akron General Hospital

Akron, Ohio, 44307, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University - Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Oklahoma University Health Sciences Center (OUHSC)

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Brain and Spine Institute

Portland, Oregon, 97225, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Penn State Univ/ Hershey Med Center

Hershey, Pennsylvania, 17033, United States

Location

Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC-Mercy Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Wellspan York Hospital

York, Pennsylvania, 17403, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Palmetto Health

Columbia, South Carolina, 29203, United States

Location

Vanderbilt Stroke Center

Nashville, Tennessee, 37232, United States

Location

Seton Medical Center Austin

Austin, Texas, 78705, United States

Location

St. David's Medical Center

Austin, Texas, 78705, United States

Location

University Medical Center Brackenridge

Austin, Texas, 78705, United States

Location

UT Southwestern - Parkland Hospital

Dallas, Texas, 75235, United States

Location

Texas Tech University Health Sciences Center

El Paso, Texas, 79430, United States

Location

Valley Baptist Medical Center

Harlingen, Texas, 78550, United States

Location

Memorial Herman - Texas Medical Center

Houston, Texas, 77024, United States

Location

Baylor College of Medicine - Ben Taub Community Hospital

Houston, Texas, 77030, United States

Location

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

Houston, Texas, 77030, United States

Location

Methodist Hospital - The Neurological Institute

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298-0631, United States

Location

West Virginia University - Ruby Memorial Hospital

Morgantown, West Virginia, 26506, United States

Location

Medical College of Wisconsin

Milwakee, Wisconsin, 53226, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

University of Alberta

Edmonton, Alberta, 2E3.27WMC, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

Location

The Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

Baotou Central Hospital

Baotou, China

Location

Beijing Tiantan Hospital

Beijing, 100050, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

Datong Third People's Hospital

Datong, China

Location

The First Hospital of Shanxi Medical University

Taiyuan, 030001, China

Location

The First People's Hospital of Taizhou

Taizhou, 318020, China

Location

Tianjin Fourth Central Hospital

Tianjin, 300140, China

Location

Wuhan Brain Hospital

Wuhan, 430019, China

Location

Renmin Hospital of Wuhan University

Wuhan, 430060, China

Location

People's Hopital of Zhengzhou

Zhengzhou, 450003, China

Location

Charité Universtity Medicine Berlin

Berlin, 12203, Germany

Location

University of Bonn

Bonn, 53105, Germany

Location

University Hospital Dresden

Dresden, 01307, Germany

Location

Clinic Frankfurt Hoechst

Frankfurt, 65929, Germany

Location

University Hospital Halle

Halle, 06120, Germany

Location

University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

University Hospital Mannheim

Mannheim, 68167, Germany

Location

University Hospital Meunster

Münster, 48129, Germany

Location

University of Tubingen

Tübingen, 72076, Germany

Location

Nagoya Medical Center

Nagoya, Aichi-ken, 460-0001, Japan

Location

Nakamura Memorial Hospital

Sapporo, Hokkaido, 060-8570, Japan

Location

Saiseikai Yokohamashi Tobu Hospital

Kanagawa, Kanagowa, 230-8765, Japan

Location

Saiseikai Kumamoto Hospital

Kumamoto, Kumamoto, 861-4193, Japan

Location

Kyushu Medical Center

Fukuoka, 810-8563, Japan

Location

Gifu University Hospital

Gifu, 501-1194, Japan

Location

St. Marianna - Toyoko

Kawasaki, 211-0063, Japan

Location

St. Marianna University Hospital

Kawasaki, 216-8511, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Japan

Location

Kawasaki Medical School

Okayama, 701-0192, Japan

Location

National Cerebral and Cardiovascular Center

Osaka, 565-8565, Japan

Location

Kohnan Hospital

Sendai, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Saiseikai Central Hospital - Tokyo

Tokyo, 108-0073, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

Kyorin University

Tokyo, Japan

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Location

Chonnam National University Hospital

Gwangju, 501-757, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Kyung Hee University Hospital

Seoul, 130-702, South Korea

Location

Seoul National University Boramae Hospital

Seoul, 156-707, South Korea

Location

Changhua Christian Hospital

Changhua, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Taichung Veterans General Hopital

Taichung, 407, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Shin-Kong Wu Ho-Su Memorial Hospital

Taipei, 111, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Taipei Veteran's Hospital

Taipei, Taiwan

Location

Related Publications (32)

  • 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.

    PMID: 20457956BACKGROUND
  • 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.

    PMID: 19770736BACKGROUND
  • 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.

    PMID: 18606927BACKGROUND
  • 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.

    PMID: 17356194BACKGROUND
  • 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.

    PMID: 21626077BACKGROUND
  • 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.

    PMID: 22560810BACKGROUND
  • 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.

    PMID: 25132910BACKGROUND
  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

Nicardipine

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DihydropyridinesPyridinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

Treatment failures, randomization window, demographics, pre-randomization treatment, low death/disability, favorable baselines, and early termination could limit generalizability of primary (all with intent-to-treat) results and some sub-analyses.

Results Point of Contact

Title
Adnan I. Qureshi, MD
Organization
University of Minnesota

Study Officials

  • Adnan I Qureshi, MD

    University of Minnesota

    STUDY CHAIR
  • Yuko Y Palesch, PhD

    Medical University of South Carolina

    STUDY DIRECTOR
  • Adnan I Qureshi, MD

    University of Minnesota

    PRINCIPAL INVESTIGATOR
  • Yuko Y Palesch, PhD

    Medical University of South Carolina

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 4, 2010

First Posted

August 6, 2010

Study Start

May 15, 2011

Primary Completion

December 21, 2015

Study Completion

March 8, 2016

Last Updated

April 25, 2017

Results First Posted

April 25, 2017

Record last verified: 2017-03

Data Sharing

IPD Sharing
Will share

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.

Locations