Antihypertensive Treatment of Acute Cerebral Hemorrhage-II

Intracerebral Hemorrhage Clinical Trial

— ATACH-II  

Official title:

Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-II: A Phase III Randomized Multicenter Clinical Trial of Blood Pressure Reduction for Hypertension in Acute Intracerebral Hemorrhage

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01176565
• Other study ID #: 1207M17921
• Secondary ID: U01NS062091U01NS
• Status: Terminated
• Phase: Phase 3
• First received: August 4, 2010
• Last updated: September 30, 2016
• Start date: May 2011
• Est. completion date: March 2016

Study information

• Verified date: September 2016
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 > 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.

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 our current pilot trials are accurate.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1000
• Est. completion date: March 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

• Note: Patients with SBP < 180mmHg 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 50,000mm3

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage

Intervention

Drug:
• Nicardipine hydrochloride
IV nicardipine will be initiated at a rate of 5 mg/hr and increased by 2.5 mg/hr increments will continue every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is > target SBP despite infusion of the maximum nicardipine dose for 30 min, a second agent can be used (Labetalol 5-20 mg IV bolus every 15 min) for another h.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
China	Baotou Central Hospital	Baotou
China	Beijing Tiantan Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Datong Third People's Hospital	Datong
China	The Second Hospital of Hebei Medical University	Shijiazhuang City	Hebei
China	The First Hospital of Shanxi Medical University	Taiyuan City
China	The Second Hospital of Shanxi Medical University	Taiyuan City	Shanxi
China	The First People's Hospital of Taizhou	Taizhou City
China	Tianjin Fourth Central Hospital	Tianjin
China	Renmin Hospital of Wuhan University	Wuhan
China	Wuhan Brain Hospital	Wuhan
China	People's Hopital of Zhengzhou	Zhengzhou
Germany	Charité Universtity Medicine Berlin	Berlin
Germany	University of Bonn	Bonn
Germany	University Hospital Dresden	Dresden
Germany	Clinic Frankfurt Hoechst	Frankfurt
Germany	University Hospital Halle	Halle (Saale)
Germany	University Hospital Heidelberg	Heidelberg
Germany	University Hospital Leipzig	Leipzig
Germany	University Hospital Mannheim	Mannheim
Germany	University Hospital Meunster	Munster
Germany	University of Tubingen	Tubingen
Japan	Kyushu Medical Center	Fukuoka
Japan	Gifu University Hospital	Gifu
Japan	Saiseikai Yokohamashi Tobu Hospital	Kanagawa	Kanagowa
Japan	St. Marianna - Toyoko	Kawasaki
Japan	St. Marianna University Hospital	Kawasaki
Japan	Kobe City Medical Center General Hospital	Kobe City
Japan	Saiseikai Kumamoto Hospital	Kumamoto City	Kumamoto
Japan	Nagoya Medical Center	Nagoya City	Aichi
Japan	Kawasaki Medical School	Okayama
Japan	National Cerebral and Cardiovascular Center	Osaka
Japan	Nakamura Memorial Hospital	Sapporo	Hokkaido
Japan	Kohnan Hospital	Sendai
Japan	Keio University Hospital	Tokyo
Japan	Kyorin University	Tokyo
Japan	Saiseikai Central Hospital - Tokyo	Tokyo
Japan	Toranomon Hospital	Tokyo
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Seoul National University Boramae Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hopital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Shin-Kong Wu Ho-Su Memorial Hospital	Taipei
Taiwan	Taipei Veteran's Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Akron General Hospital	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Mission Hospital	Asheville	North Carolina
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Seton Medical Center Austin	Austin	Texas
United States	St. David's Medical Center	Austin	Texas
United States	University Medical Center Brackenridge	Austin	Texas
United States	UAB Comprehensive Stroke Center	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mamoides Medical Center	Brooklyn	New York
United States	New York City Health and Hospitals Corp. / Kings County Hospital	Brooklyn	New York
United States	Sister of Charity/Buffalo Mercy Hospital, Catholic Health System	Buffalo	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	Medical University of South Carolina (Clinical SIte)	Charleston	South Carolina
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	St. Joseph's Regional Medical Center	Clifton	New Jersey
United States	Palmetto Health	Columbia	South Carolina
United States	Ohio State University - Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern - Parkland Hospital	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Henry Ford Health System	Detroit	Michigan
United States	Sinai-Grace Hospital	Detroit	Michigan
United States	Wayne State University - Detroit Receiving Hospital	Detroit	Michigan
United States	Essentia Health St. Mary's Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	New Jersey Neuroscience Institute, JFK Medical Center	Edison	New Jersey
United States	Texas Tech University Health Sciences Center	El Paso	Texas
United States	Colorado Neurological Institute	Englewood	Colorado
United States	Lutheran Hospital Indiana	Fort Wayne	Indiana
United States	Parkview Hospital	Fort Wayne	Indiana
United States	Community Regional Medical Center of Fresno	Fresno	California
United States	University of Florida Gainesville	Gainesville	Florida
United States	Guilford Neurologic Associates	Greenboro	North Carolina
United States	Vidant Medical Center	Greenville	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Valley Baptist Medical Center	Harlingen	Texas
United States	Penn State Univ/ Hershey Med Center	Hershey	Pennsylvania
United States	Baylor College of Medicine - Ben Taub Community Hospital	Houston	Texas
United States	Baylor College of Medicine - St. Luke's Episcopal Hospital	Houston	Texas
United States	Memorial Herman - Texas Medical Center	Houston	Texas
United States	Methodist Hospital - The Neurological Institute	Houston	Texas
United States	Eastern Idaho Medical Consultants	Idaho Falls	Idaho
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist Medical Center Jacksonville	Jacksonville	Florida
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	UHS Wilson Medical Center	Johnson City	New York
United States	Kansas University Medical Center	Kansas City	Kansas
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Neuroscience Institute	Kansas City	Missouri
United States	University of California San Diego	La Jolla	California
United States	University of Kentucky	Lexington	Kentucky
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Ronald Regan UCLA Medical Center	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	West Jefferson Medical Center	Marrero	Louisiana
United States	Loyola University Medical Center	Maywood	Illinois
United States	Medical College of Wisconsin	Milwakee	Wisconsin
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Minnesota Medical School	Minneapolis	Minnesota
United States	West Virginia University - Ruby Memorial Hospital	Morgantown	West Virginia
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt Stroke Center	Nashville	Tennessee
United States	Yale - New Haven Hospital	New Haven	Connecticut
United States	Interim LSU Hospital	New Orleans	Louisiana
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Lincoln Medical and Mental Health Center	New York	New York
United States	SUNY Downstate	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Oklahoma University Health Sciences Center (OUHSC)	Oklahoma City	Oklahoma
United States	Stanford University	Palo Alto	California
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Temple University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Maricopa Medical Center	Phoenix	Arizona
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Mercy Hospital	Pittsburgh	Pennsylvania
United States	Providence Brain and Spine Institute	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Rochester General Hospital	Rochester	New York
United States	Strong Stroke Center	Rochester	New York
United States	Sutter Roseville Medical Center	Roseville	California
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	UC Davis Medical Center	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center	San Francisco	California
United States	Good Samaritan Hospital	San Jose	California
United States	Santa Clara Valley Medical Center	Santa Clara	California
United States	Mayo Clinic Pheonix	Scottsdale	Arizona
United States	Louisiana State University Health Sciences Center, Shreveport	Shreveport	Louisiana
United States	Maine Medical Center	South Portland	Maine
United States	Southern Illinois University Memorial Medical Center	Springfield	Illinois
United States	St. Cloud Hospital	St. Cloud	Minnesota
United States	Regions Hospital	St.Paul	Minnesota
United States	University of South Florida, Tampa General Hospital	Tampa	Florida
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Banner University Medical Center - South Campus	Tuscon	Arizona
United States	Banner University Medical Center - University Campus	Tuscon	Arizona
United States	Reading Hospital	West Reading	Pennsylvania
United States	Novant Clinical Research Institute/Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest Baptist Medical Center (Wake Forest School of Medicine)	Winston-Salem	North Carolina
United States	Wellspan York Hospital	York	Pennsylvania

Sponsors (12)

Lead Sponsor

Collaborator

University of Minnesota - Clinical and Translational Science Institute

Beijing Tiantan Hospital, China Medical University Hospital, Japan Cardiovascular Research Foundation, Johns Hopkins University, Medical University of South Carolina, National Cerebral and Cardiovascular Center, National Institute of Neurological Disorders and Stroke (NINDS), Neurocritical Care Research Network, Seoul National University Hospital, University Hospital Heidelberg, University of Michigan

Countries where clinical trial is conducted

United States,  Canada,  China,  Germany,  Japan,  Korea, Republic of,  Taiwan, 

References & Publications (7)

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. — View Citation

Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz Flores S, Ehtisham A, Goldstein JN, Kirmani JF, Hussein HM, Suri MF, Tariq N; Antihypertensive Treatment of Acute Cerebral Hemorrhage Investigators. Systolic blood pressure reduction and risk of acute ren — View Citation

Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz-Flores S, Ehtisham A, Ezzeddine MA, Goldstein JN, Hussein HM, Suri MF, Tariq N; Antihypertensive Treatment of Acute Cerebral Hemorrhage Study Investigators. Effect of systolic blood pressure reduction on — View Citation

Qureshi AI, Palesch YY, Martin R, Toyoda K, Yamamoto H, Wang Y, Wang Y, Hsu CY, Yoon BW, Steiner T, Butcher K, Hanley DF, Suarez JI. Interpretation and Implementation of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT II). — View Citation

Qureshi AI, Palesch YY. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: design, methods, and rationale. Neurocrit Care. 2011 Dec;15(3):559-76. doi: 10.1007/s12028-011-9538-3. — View Citation

Qureshi AI. Acute hypertensive response in patients with stroke: pathophysiology and management. Circulation. 2008 Jul 8;118(2):176-87. doi: 10.1161/CIRCULATIONAHA.107.723874. Review. — View Citation

Qureshi AI. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design. Neurocrit Care. 2007;6(1):56-66. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A pragmatic, streamlined randomized design to evaluate the efficacy of intensive SBP reduction and its effect on outcomes measures at 24 h, 30 d and at 3 m from randomization in subjects with ICH	Primary outcome is death or disability, defined by modified Rankin scale (mRS) of 4-6 at 3 m following treatment. We chose the mRS because of its high inter-observer reliability, superiority to other indices (e.g., Barthel index), and consistency with previous trials in patients with ICH. Further reliability will be increased by training raters in using the structured interview and obtaining a mRS grade. A dichotomous outcome was chosen to reduce the rate of mis-classification and increase the sensitivity of detecting meaningful difference.	August, 2010 through 3 + 1 months margin from final subject randomization	No
Secondary	Secondary outcomes	EuroQOL: EuroQOL (EQ) is a simple, standardized non-disease-specific instrument for describing and valuating health-related quality of life. Its components are a printed 'thermometer'-type visual analogue scale and EQ-5D, which consists of 5 questions in 5 different domains and allows for responses from 1 (the best outcome) to 3 (the worst).	August, 2010 through 3 + 1 months margin from final subject randomization	No
Secondary	Secondary Outcomes	Hematoma expansion as determined by serial CT scans: Hematoma expansion will be defined as an increase in the volume of intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-h CT compared with the baseline CT scan.	August, 2010 though 3 + 1 months margin from final hospital discharge of any subject enrolled.	Yes

External Links

•   Study protocol