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Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborators:
Medical University of South Carolina
Johns Hopkins University
University of Michigan
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01176565
First received: August 4, 2010
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

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.

Condition Intervention Phase
Intracerebral Hemorrhage
Drug: Nicardipine hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • A pragmatic, streamlined randomized design to evaluate the efficacy of intensive SBP reduction and its effect on outcomes measures at 24 h and at 3 m from randomization in subjects with ICH [ Time Frame: August, 2010- July 2015 ] [ Designated as safety issue: No ]
    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 misclassification and increase the sensitivity of detecting meaningful difference.


Secondary Outcome Measures:
  • Secondary outcomes [ Time Frame: August, 2010- July 2015 ] [ Designated as safety issue: No ]

    EuroQOL: EuroQOL, 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).

    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.



Estimated Enrollment: 1280
Study Start Date: January 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard SBP Reduction Arm

Nicardipine hydrochloride will be used PRN as primary agent in lowering SBP.

The goal for the standard BP reduction group will be to reduce and maintain SBP < 180 mmHg for 24 h from randomization. 160 mmHg is the target SBP for this arm.

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.
Other Name: Cardene® I.V.
Active Comparator: Intensive SBP Reduction Arm

Nicardipine hydrochloride will be used PRN as primary agent in lowering SBP.

The goal for the intensive BP reduction group will be to reduce and maintain SBP < 140 mmHg for 24 h from randomization. 125 mmHg is the target SBP for this arm.

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.
Other Name: Cardene® I.V.

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • IV nicardipine can be initiated within 4.5 hours of symptom onset.
  • Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
  • Total GCS score (aggregate of verbal, eye, and motor response scores) of 5 or greater at time of ED arrival.
  • 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, AVM, or aneurysms.
  • Intracerebral hematoma considered to be related to trauma.
  • ICH located in infratentorial regions such as pons or cerebellum.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01176565

Contacts
Contact: Adnan I Qureshi, MD 612-626-8221 qureshai@gmail.com
Contact: Kathryn A France, PHN 763-229-3821 kafrance@umn.edu

  Hide Study Locations
Locations
United States, Alabama
UAB Comprehensive Stroke Center Recruiting
Birmingham, Alabama, United States, 35249
United States, Arizona
University of Arizona Medical Center - University Campus Recruiting
Tuscon, Arizona, United States, 85724
University of Arizona Medical Center - South Campus Recruiting
Tuscon, Arizona, United States, 85713
United States, California
Mercy San Juan Medical Center Withdrawn
Carmichael, California, United States, 95608
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Hoag Memorial Hospital Presbyterian Suspended
Newport Beach, California, United States, 92658
Stanford University Recruiting
Palo Alto, California, United States, 94304
Sutter Roseville Medical Center Recruiting
Roseville, California, United States, 95661
Mercy General Hospital Withdrawn
Sacramento, California, United States, 95815
Sutter Medical Center Withdrawn
Sacramento, California, United States, 95816
UCSF Medical Center Recruiting
San Francisco, California, United States, 94143
Santa Clara Valley Medical Center Recruiting
Santa Clara, California, United States, 95138
United States, Colorado
Colorado Neurological Institute Recruiting
Englewood, Colorado, United States, 80113
United States, Connecticut
Yale - New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
University of South Florida, Tampa General Hospital Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
St. Joseph's Candler Health System Withdrawn
Savannah, Georgia, United States, 31405
United States, Idaho
Eastern Idaho Regional Medical Center Suspended
Idaho Falls, Idaho, United States, 83404
United States, Illinois
Rush University Medical Center Withdrawn
Chicago, Illinois, United States, 60612
St. John's Hospital Recruiting
Springfield, Illinois, United States, 62769
United States, Indiana
Parkview Hospital Suspended
Fort Wayne, Indiana, United States, 46805
United States, Kansas
Kansas University Medical Center Recruiting
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40292
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
United States, Maine
Maine Medical Center Recruiting
South Portland, Maine, United States, 04106
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Boston Medical Center Suspended
Boston, Massachusetts, United States, 02118
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Wayne State University - Detroit Receiving Hospital Recruiting
Detroit, Michigan, United States, 48201
William Beaumont Hospital Recruiting
Royal Oak, Michigan, United States, 48073
Saint Louis University Suspended
Saint Louis, Michigan, United States, 63104
United States, Minnesota
Fairview Southdale Hospital Recruiting
Edina, Minnesota, United States, 55435
University of Minnesota Medical School Active, not recruiting
Minneapolis, Minnesota, United States, 55455
Hennepin County Medical Center Recruiting
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center-Fairview Withdrawn
Minneapolis, Minnesota, United States, 55455
St. Cloud Hospital Recruiting
St. Cloud, Minnesota, United States, 56303
Regions Hospital Recruiting
St.Paul, Minnesota, United States, 55101
United States, Mississippi
University of Mississippi Medical Center Suspended
Jackson, Mississippi, United States, 39216
United States, Missouri
Research Medical Center Recruiting
Kansas City, Missouri, United States, 64132
St. Luke's Neuroscience Institute Suspended
Kansas City, Missouri, United States, 64111
Mercy Hospital Withdrawn
St. Louis, Missouri, United States, 63141
United States, New Jersey
St. Joseph's Regional Medical Center Recruiting
Clifton, New Jersey, United States, 07012
New Jersey Neuroscience Institute, JFK Medical Center Recruiting
Edison, New Jersey, United States, 08818
United States, New Mexico
University of New Mexico Recruiting
Albuquerque, New Mexico, United States, 87131
United States, New York
Albany Medical College Withdrawn
Albany, New York, United States, 12208
New York City Health and Hospitals Corp. / Kings County Hospital Recruiting
Brooklyn, New York, United States, 11203
UHS Wilson Medical Center Recruiting
Johnson City, New York, United States, 13790
Columbia University Recruiting
New York, New York, United States, 10032
SUNY Downstate Recruiting
New York, New York, United States, 10029
United States, North Carolina
Guilford Neurologic Associates Recruiting
Greenboro, North Carolina, United States, 27405
Novant Clinical Research Institute/Forsyth Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27103
Wake Forest School of Medicine Withdrawn
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Akron General Hospital Recruiting
Akron, Ohio, United States, 44307
University Hospitals Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Ohio State University - Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
United States, Oklahoma
Oklahoma University Health Sciences Center (OUHSC) Suspended
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Providence Brain and Spine Institute Suspended
Portland, Oregon, United States, 97225
United States, Pennsylvania
Abington Memorial Hospital Recruiting
Abington, Pennsylvania, United States, 19001
Lehigh Valley Health Network Suspended
Allentown, Pennsylvania, United States, 18103
Penn State Univ/ Hershey Med Center Recruiting
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
UPMC Presbyterian Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
United States, South Carolina
Palmetto Health Recruiting
Columbia, South Carolina, United States, 29203
United States, Tennessee
Vanderbilt Stroke Center Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
Valley Baptist Medical Center Recruiting
Harlingen, Texas, United States, 78550
Baylor College of Medicine - St. Luke's Episcopal Hospital Recruiting
Houston, Texas, United States, 77030
Baylor College of Medicine - Ben Taub Community Hospital Recruiting
Houston, Texas, United States, 77030
Memorial Herman - Texas Medical Center Recruiting
Houston, Texas, United States, 77024
United States, Virginia
Virginia Commonwealth University Medical Center Recruiting
Richmond, Virginia, United States, 23298-0631
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwakee, Wisconsin, United States, 53226
China, Liaoning
The First Affiliated Hospital of Liaoning Medical College Withdrawn
Jinzhou, Liaoning, China, 121001
China
Baotou Central Hospital Suspended
Baotou, China
Beijing Tiantan Hospital Recruiting
Beijing, China, 100050
Datong Third People's Hospital Recruiting
Datong, China
The First People's Hospital of Taizhou Recruiting
Taizhou City, China, 318020
Wuhan Brain Hospital Recruiting
Wuhan, China, 430019
Tongji Medical College - Union Hospital Recruiting
Wuhan, China
Germany
Charité Universtity Medicine Berlin Recruiting
Berlin, Germany, 12203
University of Bonn Recruiting
Bonn, Germany, 53105
Clinic Frankfurt Hoechst Recruiting
Frankfurt, Germany, 65929
University Hospital Halle Recruiting
Halle (Saale), Germany, 06120
University Hospital Heidelberg Recruiting
Heidelberg, Germany, 69120
University Hospital Leipzig Recruiting
Leipzig, Germany, 04103
University Hospital Mannheim Recruiting
Mannheim, Germany, 68167
University of Tubingen Recruiting
Tubingen, Germany, 72076
Japan
Nagoya Medical Center Recruiting
Nagoya City, Aichi, Japan, 460-0001
Nakamura Memorial Hospital Recruiting
Sapporo, Hokkaido, Japan, 060-8570
Kyushu Medical Center Recruiting
Fukuoka, Japan, 810-8563
Gifu University Hospital Recruiting
Gifu, Japan, 501-1194
Saiseikai Yokohamashi Tobu Hospital Recruiting
Kanagawa, Japan
St. Marianna - Toyoko Recruiting
Kawasaki, Japan, 211-0063
St. Marianna University Hospital Recruiting
Kawasaki, Japan, 216-8511
Kobe City Medical Center General Hospital Recruiting
Kobe City, Japan
Kawasaki Medical School Suspended
Okayama, Japan, 701-0192
National Cerebral and Cardiovascular Center Recruiting
Osaka, Japan, 565-8565
Kohnan Hospital Recruiting
Sendai, Japan
Kyorin University Suspended
Tokyo, Japan
Toranomon Hospital Recruiting
Tokyo, Japan, 105-8470
Keio University Hospital Recruiting
Tokyo, Japan, 160-8582
Saiseikai Central Hospital - Tokyo Recruiting
Tokyo, Japan, 108-0073
Korea, Republic of
Hallym University Sacred Heart Hospital Withdrawn
Anyang, Gyeonggi, Korea, Republic of, 431070
Seoul National University Bundang Hospital Recruiting
Seongnam, Gyeonggi, Korea, Republic of
Inje University Pusan Paik Hospital Withdrawn
Busan, Korea, Republic of
Asan Medical Center Withdrawn
Seoul, Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Taiwan
China Medical University Beigang Hospital Recruiting
Beigang, Taiwan
Changhua Christian Hospital Recruiting
Changhua, Taiwan
Kaohsiung Veterans General Hospital Recruiting
Kaohsiung City, Taiwan
China Medical University Hospital Recruiting
Taichung, Taiwan, 404
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan
Taipei Veterans Hospital Recruiting
Taipei, Taiwan, 11217
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Tri-Service General Hospital Recruiting
Taipei, Taiwan, 114
Shin-Kong Wu Ho-Su Memorial Hospital Recruiting
Taipei, Taiwan, 111
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Medical University of South Carolina
Johns Hopkins University
University of Michigan
Investigators
Study Director: Yuko Y Palesch, Ph.D. Medical University of South Carolina
Principal Investigator: Adnan I Qureshi, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01176565     History of Changes
Other Study ID Numbers: h, 1U01NS062091-01, U01NS061861
Study First Received: August 4, 2010
Last Updated: September 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Acute hypertensive response
intracerebral hemorrhage
blood pressure
outcome
nicardipine

Additional relevant MeSH terms:
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Nicardipine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on October 19, 2014