Antihypertensive Treatment in Acute Cerebral Hemorrhage - Full Text View

Sponsors and Collaborators:	University of Minnesota National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier:	NCT00415610

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 I

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Nicardipine Nicardipine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:

Tolerability, the ability to achieve reduction of blood pressure and maintain treatment goals (the specified systolic blood pressure range for the 18-24 hour period) without neurological deterioration or side effects [ Time Frame: 18-24 hour period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety, 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 ]

Estimated Enrollment:	60
Study Start Date:	July 2005
Estimated Study Completion Date:	May 2008
Estimated Primary Completion Date:	May 2008 (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 at 170 to 200 mmHg	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.
Tier 2 Dose escalation the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 140 to 170 mmHg	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.
Tier 3 Dose escalation the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 110 to 140 mmHg	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.

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
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

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
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63108
United States, New Jersey
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, United States, 07107
JFK Medical Center
Edison, New Jersey, United States, 08818
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, South Carolina
Statistical Coordinating Center: Medical University of South Carolina
Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

University of Minnesota

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Adnan I. Qureshi, MD	University of Minnesota
Investigator:	Yuko Palesch, Ph.D.	Study Statistician, Medical University of South Carolina
Investigator:	Jill Novitzke, RN	Clinical Coordinator, University of Minnesota
Investigator:	Catherine Dillon	Project Manager, Medical University of South Carolina

More Information

Responsible Party:	University of Minnesota ( Adnan I. Qureshi, MD, ATACH Principal Investigator, Executive Director, Stroke Center, Associate Head, Department of Neurology Professor of Neurology, Neurosurgery, and Radiology )
Study ID Numbers:	R01NS44976-01A2
Study First Received:	December 21, 2006
Last Updated:	December 28, 2007
ClinicalTrials.gov Identifier:	NCT00415610
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):

cerebral hemorrhage
intracerebral hemorrhage
stroke
hypertension

blood pressure
nicardipine
antihypertensive agent
hematoma expansion

Study placed in the following topic categories:

Cerebral Hemorrhage
Cerebral Infarction
Stroke
Vascular Diseases
Central Nervous System Diseases
Intracranial Hemorrhages
Hemorrhage

Brain Diseases
Cerebrovascular Disorders
Hematoma
Calcium, Dietary
Nicardipine
Hypertension

Additional relevant MeSH terms:

Membrane Transport Modulators
Vasodilator Agents
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Nervous System Diseases

Calcium Channel Blockers
Cardiovascular Diseases
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009