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Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

This study has been completed.
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00415610
First received: December 21, 2006
Last updated: August 10, 2015
Last verified: August 2015
  Purpose
The purpose of this trial is to evaluate the safety and effectiveness of lowering blood pressure using nicardipine in persons with acute hypertension associated with intracerebral hemorrhage.

Condition Intervention Phase
Intracerebral Hemorrhage
Hypertension
Stroke
Drug: nicardipine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Feasibility, the Ability to Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier. [ Time Frame: Within 3 hours of symptom onset and sustained through 18-24 hours. ] [ Designated as safety issue: No ]
    Feasibility of treatment was assessed by whether SBP reduction and maintenance within the respective target range was achieved (treatment success) or not (treatment failure), and secondarily by whether a significant difference between treatment arms was achieved. Treatment failure was defined based on the observed hourly hourly minimum SBP remaining greater than the upper limit of the target range for 2 consecutive hours after initiation of nicardipine infusion. Spontaneous decline of SBP below the lower limit of the specific tier was not considered treatment failure as all such declines were asymptomatic.The lower number in the more intensive treatment groups reflects in part the greater challenge of rapidly lowering systolic blood pressure to a more intensive (lower) range, as a higher number of treatment failures as pre-defined by meeting the SBP range goal within 3 hours of symptom onset in this group predictably occurred.

  • Safety, Acute, as Determined by the Amount of Neurological Deteriorations During the 24 Hour Treatment Period, Plus the Number of Serious Adverse Events. [ Time Frame: within the first 72 hours of treatment initiation ] [ Designated as safety issue: Yes ]
    Safety outcomes were defined as the rate of neurological deterioration during treatment, and the rate of serious adverse events related to nicardipine. Safety stopping rules were pre-specified and were overseen by an external DSMB. Because SBP reduction may progress variably, additional analyses were also done to examine the relationship between SBP reduction and safety events more closely. The average SBP change at 2 hours after treatment initiation was compared among subjects who did or did not have neurological deterioration within 24 hours to evaluate the relationship between early SBP reduction and safety events. For each subject who experienced neurological deterioration (ND) within 24 hours, a graph of average hourly SBP and nicardipine dose was examined with timing of the ND noted. Therefore safety was evaluated according to assigned treatment group and also according to actual treatment magnitude within a clinically meaningful timeline for all subjects enrolled.


Secondary Outcome Measures:
  • Tolerability, the Ability of Subjects to Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects


Enrollment: 60
Study Start Date: July 2005
Study Completion Date: March 2008
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Tier 1

Dose escalation:

The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 170 to 200 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Drug: nicardipine

Intravenous (IV) nicardipine infusion. It is expected that the treatment duration will vary between 18 and 24 hours.

  • Started at 5mg/h
  • Titrated by 2.5mg/hour every 15 minutes to bring systolic blood pressure in target range for the applicable Tier. Max dose 15mg/hour *Once target systolic blood pressure reached, dose decreased by 2.5mg/hour every 15 minutes until systolic blood pressure maintained in the target range or the medication is discontinued.
Other Name: Cardene, nicardipine hydrochloride
Tier 2

Dose escalation:

The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 140 to 170 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Drug: nicardipine

Intravenous (IV) nicardipine infusion. It is expected that the treatment duration will vary between 18 and 24 hours.

  • Started at 5mg/h
  • Titrated by 2.5mg/hour every 15 minutes to bring systolic blood pressure in target range for the applicable Tier. Max dose 15mg/hour *Once target systolic blood pressure reached, dose decreased by 2.5mg/hour every 15 minutes until systolic blood pressure maintained in the target range or the medication is discontinued.
Other Name: Cardene, nicardipine hydrochloride
Tier 3

Dose escalation:

The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 110 to 140 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Drug: nicardipine

Intravenous (IV) nicardipine infusion. It is expected that the treatment duration will vary between 18 and 24 hours.

  • Started at 5mg/h
  • Titrated by 2.5mg/hour every 15 minutes to bring systolic blood pressure in target range for the applicable Tier. Max dose 15mg/hour *Once target systolic blood pressure reached, dose decreased by 2.5mg/hour every 15 minutes until systolic blood pressure maintained in the target range or the medication is discontinued.
Other Name: Cardene, nicardipine hydrochloride

Detailed Description:

An estimated 37,000 to 52,400 people in the United States have intracerebral hemorrhage (ICH) every year. ICH——a form of stroke that has poor outcome and is difficult to treat——is associated with the highest mortality rate of all strokes. Hematoma expansion has been identified as the most common cause of neurological deterioration in persons with ICH. Early evidence suggests that acute hypertension (HTN)—or elevated blood pressure—may make some individuals more susceptible to hematoma expansion. Treating HTN acutely may prevent hematoma expansion, however, the effect of aggressive HTN treatment has not been determined.

The purpose of this trial is to evaluate the treatment feasibility and safety of lowering blood pressure using nicardipine——an antihypertensive medication——in persons who have acute HTN associated with ICH.

This pilot study will enroll 60 individuals who qualify with a presenting systolic blood pressure of at least 170 mmHg, have an ICH, and can be evaluated and treatment initiated within 6 hours of onset of stroke symptoms. In a stepwise fashion, the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 3 sequential levels: 170 to 200 mmHg, 140 to 170 mmHg, and 110 to 140 mmHg. Twenty participants will be enrolled per level.

Treatment will last 18 to 24 hours. Participants will stay in the hospital for about 7 days (including 24 hours in the intensive care unit for close monitoring) and will return for 1-hour follow-up visits at 30 days and at 90 days after discharge from the hospital. During these visits participants will receive neurological assessments to determine their functional outcome. For participants, the study will be completed after the 90-day follow-up visit.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age older than 18 years.
  • Onset of new neurological signs of a stroke within 12 hours of the time to evaluation AND initiation of treatment with intravenous nicardipine.
  • Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
  • The total GCS score is greater than 8 at the time of enrollment.
  • CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement less than 60 cc.
  • ICH is supratentorial and is located in lobar, basal ganglionic, or thalamic based on the initial CT scan appearance.
  • Admission systolic blood pressure greater than 170 mm Hg on two repeat measurements at least 5 minutes apart.
  • Evidence of chronic hypertension.
  • Subject is not considered a surgical candidate by the neurosurgery service.

Exclusion Criteria:

  • Time of symptom onset cannot be reliably assessed.
  • Previously known neoplasms, arteriovenous malformation, or aneurysms.
  • Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon.
  • ICH is located in the cortex or infratentorial regions such as pons or cerebellum.
  • Blood is visualized in the subarachnoid space.
  • Intravenous nicardipine cannot be initiated within 12 hours of symptom onset.
  • Use of clonidine hydrochloride and other central alpha-agonist within the last 48 hours that have the potential of withdrawal hypertension.
  • Pregnancy, lactation, or parturition within previous 30 days.
  • Any history of bleeding diathesis or coagulopathy, including the use of warfarin.
  • Use of heparin in the previous 48 hours and a prolonged partial thromboplastin time.
  • Known atrial-ventricular heart block other than first degree, or sick sinus syndrome without a pacemaker.
  • Intolerance to calcium channel blockers.
  • Exposure to study medication in the preceding 24 hours prior to enrollment.
  • A platelet counts less than 100 000/mm3.
  • Major surgery within the previous six weeks.
  • History of any intracranial hemorrhage (including intracerebral or subarachnoid hemorrhage) or hemorrhagic stroke.
  • Seizure at onset of stroke.
  • Blood glucose less than 50 mg/dL or greater than 400 mg/dL.
  • Current participation in another research drug treatment protocol.
  • Isolated ventricular blood on CT scan.
  • Subject has a living will that precludes aggressive intensive care unit management.
  • Subject has acute myocardial infarction or renal failure that precludes use of aggressive antihypertensive therapy.
  • Subjects with unstable angina or acute myocardial infarction within 2 weeks prior to ICH.
  • Subjects with renal insufficiency with serum creatinine greater than 2.0 mg/dl or on renal dialysis.
  • Sinus tachycardia exceeding 120 beats per minute or supraventricular tachycardia is observed during initial evaluation.
  • Ischemic stroke within 4 weeks of presentation.
  • Congestive heart failure graded as class III and IV by New York Heart Association (NYHA) classification.
  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: NCT00415610

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90033
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General/Brigham Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Clinical Coordinating Center: University of Minnesota, Fairview Hospital
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63108
United States, New Jersey
JFK Medical Center
Edison, New Jersey, United States, 08818
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, United States, 07107
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Ohio State University
Columbus, Ohio, United States, 43210
United States, South Carolina
Statistical Coordinating Center: Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Adnan I. Qureshi, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

Publications:

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: NCT00415610     History of Changes
Other Study ID Numbers: 0609M93128  R01NS044976-01A2 
Study First Received: December 21, 2006
Results First Received: March 3, 2015
Last Updated: August 10, 2015
Health Authority: United States: Federal Government

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
cerebral hemorrhage
intracerebral hemorrhage
stroke
hypertension
blood pressure
nicardipine
antihypertensive agent
hematoma expansion

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

ClinicalTrials.gov processed this record on December 02, 2016