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

March 13, 2017 updated by: University of Minnesota

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

1000

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, 2E3.27WMC
        • University of Alberta
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute and Hospital
  • China
      • Baotou, China
        • Baotou Central Hospital
      • Beijing, China, 100191
        • Peking University Third Hospital
      • Beijing, China, 100050
        • Beijing Tiantan Hospital
      • Datong, China
        • Datong Third People's Hospital
      • Taiyuan City, China, 030001
        • The First Hospital of Shanxi Medical University
      • Taizhou City, China, 318020
        • The First People's Hospital of Taizhou
      • Tianjin, China, 300140
        • Tianjin Fourth Central Hospital
      • Wuhan, China, 430060
        • Renmin Hospital of Wuhan University
      • Wuhan, China, 430019
        • Wuhan Brain Hospital
      • Zhengzhou, China, 450003
        • People's Hopital of Zhengzhou
    • Hebei
      • Shijiazhuang City, Hebei, China, 050000
        • The Second Hospital of Hebei Medical University
    • Shanxi
      • Taiyuan City, Shanxi, China, 030001
        • The Second Hospital of Shanxi Medical University
  • Germany
      • Berlin, Germany, 12203
        • Charité Universtity Medicine Berlin
      • Bonn, Germany, 53105
        • University of Bonn
      • Dresden, Germany, 01307
        • University Hospital Dresden
      • Frankfurt, Germany, 65929
        • Clinic Frankfurt Hoechst
      • Halle (Saale), Germany, 06120
        • University Hospital Halle
      • Heidelberg, Germany, 69120
        • University Hospital Heidelberg
      • Leipzig, Germany, 04103
        • University Hospital Leipzig
      • Mannheim, Germany, 68167
        • University Hospital Mannheim
      • Munster, Germany, 48129
        • University Hospital Meunster
      • Tubingen, Germany, 72076
        • University of Tubingen
  • Japan
      • Fukuoka, Japan, 810-8563
        • Kyushu Medical Center
      • Gifu, Japan, 501-1194
        • Gifu University Hospital
      • Kawasaki, Japan, 211-0063
        • St. Marianna - Toyoko
      • Kawasaki, Japan, 216-8511
        • St. Marianna University Hospital
      • Kobe City, Japan
        • Kobe City Medical Center General Hospital
      • Okayama, Japan, 701-0192
        • Kawasaki Medical School
      • Osaka, Japan, 565-8565
        • National Cerebral and Cardiovascular Center
      • Sendai, Japan
        • Kohnan Hospital
      • Tokyo, Japan, 160-8582
        • Keio University Hospital
      • Tokyo, Japan, 105-8470
        • Toranomon Hospital
      • Tokyo, Japan, 108-0073
        • Saiseikai Central Hospital - Tokyo
      • Tokyo, Japan
        • Kyorin University
    • Aichi
      • Nagoya City, Aichi, Japan, 460-0001
        • Nagoya Medical Center
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8570
        • Nakamura Memorial Hospital
    • Kanagowa
      • Kanagawa, Kanagowa, Japan, 230-8765
        • Saiseikai Yokohamashi Tobu Hospital
    • Kumamoto
      • Kumamoto City, Kumamoto, Japan, 861-4193
        • Saiseikai Kumamoto Hospital
  • Korea, Republic of
      • Gwangju, Korea, Republic of, 501-757
        • Chonnam National University Hospital
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 156-707
        • Seoul National University Boramae Hospital
      • Seoul, Korea, Republic of, 130-702
        • Kyung Hee University Hospital
    • Gyeonggi
      • Seongnam, Gyeonggi, Korea, Republic of
        • Seoul National University Bundang Hospital
  • Taiwan
      • Changhua, Taiwan
        • Changhua Christian Hospital
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Hospital
      • Kaohsiung City, Taiwan
        • Kaohsiung Veterans General Hospital
      • Taichung, Taiwan, 404
        • China Medical University Hospital
      • Taichung City, Taiwan, 407
        • Taichung Veterans General Hopital
      • Tainan, Taiwan
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taipei, Taiwan, 114
        • Tri-Service General Hospital
      • Taipei, Taiwan, 111
        • Shin-Kong Wu Ho-Su Memorial Hospital
      • Taipei, Taiwan
        • Taipei Veteran's Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • UAB Comprehensive Stroke Center
    • Arizona
      • Phoenix, Arizona, United States, 85008
        • Maricopa Medical Center
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Pheonix
      • Tuscon, Arizona, United States, 85713
        • Banner University Medical Center - South Campus
      • Tuscon, Arizona, United States, 85724
        • Banner University Medical Center - University Campus
    • California
      • Fresno, California, United States, 93721
        • Community Regional Medical Center of Fresno
      • La Jolla, California, United States, 92093
        • University of California San Diego
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Medical Center
      • Los Angeles, California, United States, 90095-9574
        • Ronald Regan UCLA Medical Center
      • Newport Beach, California, United States, 92658
        • HOAG Memorial Hospital Presbyterian
      • Palo Alto, California, United States, 94304
        • Stanford University
      • Roseville, California, United States, 95661
        • Sutter Roseville Medical Center
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
      • San Jose, California, United States, 95124
        • Good Samaritan Hospital
      • Santa Clara, California, United States, 95138
        • Santa Clara Valley Medical Center
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Colorado Neurological Institute
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale - New Haven Hospital
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Hospital
    • Florida
      • Gainesville, Florida, United States, 32611
        • University of Florida Gainesville
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Jacksonville
      • Jacksonville, Florida, United States, 32207
        • Baptist Medical Center Jacksonville
      • Tampa, Florida, United States, 33612
        • University of South Florida, Tampa General Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Atlanta, Georgia, United States, 30303
        • Grady Memorial Hospital
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
    • Idaho
      • Idaho Falls, Idaho, United States, 83404
        • Eastern Idaho Medical Consultants
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Christ Medical Center
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
      • Springfield, Illinois, United States, 62794-9643
        • Southern Illinois University Memorial Medical Center
    • Indiana
      • Fort Wayne, Indiana, United States, 46805
        • Parkview Hospital
      • Fort Wayne, Indiana, United States, 46804
        • Lutheran Hospital Indiana
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Kansas University Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0296
        • University of Kentucky
      • Louisville, Kentucky, United States, 40292
        • University of Louisville
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • West Jefferson Medical Center
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
      • New Orleans, Louisiana, United States, 70112
        • Interim LSU Hospital
      • Shreveport, Louisiana, United States, 71103
        • Louisiana State University Health Sciences Center, Shreveport
    • Maine
      • South Portland, Maine, United States, 04106
        • Maine Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham & Women's Hospital
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Detroit, Michigan, United States, 48235
        • Sinai-Grace Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University - Detroit Receiving Hospital
      • Jackson, Michigan, United States, 49201
        • Allegiance Health
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Essentia Health St. Mary's Medical Center
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Minneapolis, Minnesota, United States, 55404
        • Hennepin County Medical Center
      • St. Cloud, Minnesota, United States, 56303
        • St. Cloud Hospital
      • St.Paul, Minnesota, United States, 55101
        • Regions Hospital
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Research Medical Center
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Neuroscience Institute
      • Saint Louis, Missouri, United States, 63104
        • Saint Louis University
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital
      • Clifton, New Jersey, United States, 07012
        • St. Joseph's Regional Medical Center
      • Edison, New Jersey, United States, 08818
        • New Jersey Neuroscience Institute, JFK Medical Center
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico
    • New York
      • Brooklyn, New York, United States, 11203
        • New York City Health and Hospitals Corp. / Kings County Hospital
      • Brooklyn, New York, United States, 11219
        • Mamoides Medical Center
      • Buffalo, New York, United States, 14214
        • Sister of Charity/Buffalo Mercy Hospital, Catholic Health System
      • Johnson City, New York, United States, 13790
        • UHS Wilson Medical Center
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10029
        • SUNY Downstate
      • New York, New York, United States, 10451
        • Lincoln Medical and Mental Health Center
      • Rochester, New York, United States, 14621
        • Rochester General Hospital
      • Rochester, New York, United States, 14642
        • Strong Stroke Center
    • North Carolina
      • Asheville, North Carolina, United States, 28801-4601
        • Mission Hospital
      • Greenboro, North Carolina, United States, 27405
        • Guilford Neurologic Associates
      • Greenville, North Carolina, United States, 27834
        • Vidant Medical Center
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Clinical Research Institute/Forsyth Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Medical Center (Wake Forest School of Medicine)
    • Ohio
      • Akron, Ohio, United States, 44307
        • Akron General Hospital
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University - Wexner Medical Center
      • Toledo, Ohio, United States, 43614
        • University of Toledo Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Health Sciences Center (OUHSC)
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Brain and Spine Institute
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Memorial Hospital
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Health Network
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Univ/ Hershey Med Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19102
        • Hahnemann University Hospital
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Presbyterian Hospital
      • Pittsburgh, Pennsylvania, United States, 15219
        • UPMC-Mercy Hospital
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • York, Pennsylvania, United States, 17403
        • Wellspan York Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Palmetto Health
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Stroke Center
    • Texas
      • Austin, Texas, United States, 78705
        • Seton Medical Center Austin
      • Austin, Texas, United States, 78705
        • St. David's Medical Center
      • Austin, Texas, United States, 78705
        • University Medical Center Brackenridge
      • Dallas, Texas, United States, 75235
        • UT Southwestern - Parkland Hospital
      • El Paso, Texas, United States, 79430
        • Texas Tech University Health Sciences Center
      • Harlingen, Texas, United States, 78550
        • Valley Baptist Medical Center
      • Houston, Texas, United States, 77024
        • Memorial Herman - Texas Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine - Ben Taub Community Hospital
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine - St. Luke's Episcopal Hospital
      • Houston, Texas, United States, 77030
        • Methodist Hospital - The Neurological Institute
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
    • Virginia
      • Richmond, Virginia, United States, 23298-0631
        • Virginia Commonwealth University Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University - Ruby Memorial Hospital
    • Wisconsin
      • Milwakee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora St. Luke's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Standard SBP Reduction Arm

Intravenous nicardipine hydrochloride will be used as necessary (pro re nata or "PRN") as the primary agent in lowering SBP.

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

For the standard group, SBP below the assigned treatment range is not artificially elevated to stay within the range if lower SBP occurs with nicardipine turned off (no fluid bolus given unless SBP falls below 110 mmHg with nicardipine off and there is risk for hypotension). Euvolemic fluid maintenance is encouraged for all patients according to their medical needs, which may differ.
Drug: Intravenous nicardipine hydrochloride

IV nicardipine is initiated at a rate of 5 mg/hr, is continued, and is increased by 2.5 mg/hr increments every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is above the target SBP despite infusion of the maximum nicardipine dose for 30 minutes, a second agent may be used (Labetalol 5-20 mg IV bolus every 15 min; diltiazem/urapidil in countries without labetalol) for another hour. Nicardipine infusion is decreased incrementally or is stopped if SBP falls below the desired treatment range.

Fluid bolus for SBP still falling below 110 mmHG (millimeters of mercury) with nicardipine off is given to prevent organ hypoperfusion. Vasopressor agents are not used unless symptoms related to or possibly exacerbated by hypoperfusion are present.

Other Names:
  • nicardipine
  • Cardene® I.V.
  • Nicardipine HCl injection
  • nicardipine hydrochloride injection
  • nicardipine IV
  • nicardipine hydrochloride
ACTIVE_COMPARATOR: Intensive SBP Reduction Arm

Intravenous nicardipine hydrochloride will be used as necessary (pro re nata or "PRN") as the primary agent in lowering SBP.

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

For the intensive group, SBP falling below 110 mmHg (lower limit of the assigned treatment range) with nicardipine off is treated with normal saline fluid bolus to prevent or remedy hypotension. Euvolemic fluid maintenance is encouraged for all patients according to their medical needs, which may differ.
Drug: Intravenous nicardipine hydrochloride

IV nicardipine is initiated at a rate of 5 mg/hr, is continued, and is increased by 2.5 mg/hr increments every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is above the target SBP despite infusion of the maximum nicardipine dose for 30 minutes, a second agent may be used (Labetalol 5-20 mg IV bolus every 15 min; diltiazem/urapidil in countries without labetalol) for another hour. Nicardipine infusion is decreased incrementally or is stopped if SBP falls below the desired treatment range.

Fluid bolus for SBP still falling below 110 mmHG (millimeters of mercury) with nicardipine off is given to prevent organ hypoperfusion. Vasopressor agents are not used unless symptoms related to or possibly exacerbated by hypoperfusion are present.

Other Names:
  • nicardipine
  • Cardene® I.V.
  • Nicardipine HCl injection
  • nicardipine hydrochloride injection
  • nicardipine IV
  • nicardipine hydrochloride

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurological Deterioration Within 24 Hours, Defined by a Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score From Baseline, Not Related to Sedation or Hypnotic-agent Use and Sustained for at Least 8 Hours.
Time Frame: From randomization through the 24-hour treatment period
Neurologic deterioration was measured using two scales. The Glasgow Coma Scale (GCS) score measures of level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired. The National Institutes of Health Stroke Scale (NIHSS) quantifies neurologic deficits in 11 categories. Level of consciousness, horizontal eye movement, visual fields, facial palsy, movement in each limb, sensation, language & speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42, with 0 indicating normal function and higher scores indicating greater deficit severity. Neurological status was checked per ICU standards through 24 hours, recommended as hourly GCS and full assessment every 2 hours. NIHSS assessment at baseline and 24 +/- 3 hours was pre-specified. Assessments were added for suspected neurological change.
From randomization through the 24-hour treatment period
Hypotension Within 72 Hours
Time Frame: From randomization through 72 hours from randomization
Hypotension (abnormally low blood pressure) was the most likely adverse event that could be associated with the study treatment, and is the primary basis (risk) on which neurological deterioration or other untoward effects of the study treatment could occur. It is therefore examined as a numerically-measured occurrence in addition to monitoring patients closely for neurological deterioration or other symptoms. Hypotension, when named as an adverse event, was defined as the syndrome of low blood pressure with SBP < 85 mmHg. Instances of hypotension were to be avoided through close monitoring, and administration of fluid bolus for SBP < 110 mmHg. If hypotension did occur, it was to be reversed as quickly as possible through discontinuation of intravenous nicardipine and intravenous fluid administration, which can be accomplished readily in a variety of settings where patients with intracerebral hemorrhage are routinely housed during early hospitalization.
From randomization through 72 hours from randomization
Treatment-related Serious Adverse Event Within 72 Hours of Randomization
Time Frame: From randomization through 72 hours (3 days)
Adverse events (AEs) and serious adverse events (SAEs) were assessed by the site investigators for all patients, including for their potential relatedness to the study treatment. An Independent Oversight Committee (IOC) reviewed and adjudicated all adverse event data. The 72-hours-from-randomization time window was considered the most likely time frame during which treatment-related adverse events or serious adverse events would be observed. Terminology from the Medical Dictionary for Regulatory Activities (MedDRA) and severity criteria from the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03) were used as a basis for reporting adverse events. Serious adverse events are defined as being fatal, life-threatening, resulting in hospitalization or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage and were required to be reported promptly.
From randomization through 72 hours (3 days)
Any Serious Adverse Event Within the 90-day Study Period
Time Frame: From randomization through the 90 day visit (90 ± 14 days per protocol window; up to ± 30 days data is used) or until known death, withdrawal, or loss to follow-up.
The complete count of all subjects who experienced any serious adverse events throughout their participation in the trial was included in this tabulation. Adverse events (AEs) and serious adverse events (SAEs) were assessed by the site investigators for all patients. Potential relatedness to the study treatment was a required reporting element for all adverse events but was not considered in this count. Terminology from the Medical Dictionary for Regulatory Activities (MedDRA) and severity criteria from the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03) were used as a basis for reporting adverse events. Serious adverse events are defined as being fatal, life-threatening, resulting in hospitalization or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage and were required to be reported promptly. An Independent Oversight Committee (IOC) reviewed and adjudicated adverse event data.
From randomization through the 90 day visit (90 ± 14 days per protocol window; up to ± 30 days data is used) or until known death, withdrawal, or loss to follow-up.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

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

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 15, 2011

Primary Completion (ACTUAL)

December 21, 2015

Study Completion (ACTUAL)

March 8, 2016

Study Registration Dates

First Submitted

August 4, 2010

First Submitted That Met QC Criteria

August 4, 2010

First Posted (ESTIMATE)

August 6, 2010

Study Record Updates

Last Update Posted (ACTUAL)

April 25, 2017

Last Update Submitted That Met QC Criteria

March 13, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1207M17921
  • U01NS062091 (NIH)
  • U01NS061861 (NIH)
  • U01NS059041 (NIH)
  • U01NS056975 (NIH)
  • H23-4-3 (OTHER_GRANT: Intramural Research Fund for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center, Japan)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

A public use data set from the study database will be made available. A process for sharing subject head imaging studies that may be associated with the data set is under evaluation.

Study Data/Documents

  1. Study Protocol
    Information identifier: Protocol

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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