Antihypertensive Treatment in Acute Cerebral Hemorrhage

NCT ID: NCT00415610

Last Updated: 2017-11-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2008-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Intracerebral Hemorrhage Hypertension Stroke

Keywords

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cerebral hemorrhage intracerebral hemorrhage stroke hypertension blood pressure nicardipine antihypertensive agent hematoma expansion

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Staged intensity levels of rapid intravenous antihypertensive control for elevated SBP in patients with intracerebral hemorrhage were implemented in 3 sequential treatment arms to assess the feasibility and tolerability (safety) of this treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open treatment assignment was employed because it is not safe to conceal SBP measurement. Patient data routinely entered by clinical staff were used to evaluate safety.

Study Groups

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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.

Group Type OTHER

nicardipine

Intervention Type DRUG

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 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.

Group Type OTHER

nicardipine

Intervention Type DRUG

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 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.

Group Type OTHER

nicardipine

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Cardene, nicardipine hydrochloride

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adnan I. Qureshi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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University of Southern California

Los Angeles, California, United States

Site Status

Kansas University Medical Center

Kansas City, Kansas, United States

Site Status

The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center

Kansas City, Kansas, United States

Site Status

Massachusetts General/Brigham Women's Hospital

Boston, Massachusetts, United States

Site Status

Clinical Coordinating Center: University of Minnesota, Fairview Hospital

Minneapolis, Minnesota, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

JFK Medical Center

Edison, New Jersey, United States

Site Status

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Statistical Coordinating Center: Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Countries

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United States

References

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Qureshi AI. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design. Neurocrit Care. 2007;6(1):56-66. doi: 10.1385/ncc:6:1:56.

Reference Type BACKGROUND
PMID: 17356194 (View on PubMed)

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 hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol. 2010 May;67(5):570-6. doi: 10.1001/archneurol.2010.61.

Reference Type RESULT
PMID: 20457956 (View on PubMed)

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.

Reference Type RESULT
PMID: 19770736 (View on PubMed)

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. No abstract available.

Reference Type RESULT
PMID: 18606927 (View on PubMed)

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 renal injury in patients with intracerebral hemorrhage. Am J Med. 2012 Jul;125(7):718.e1-6. doi: 10.1016/j.amjmed.2011.09.031. Epub 2012 May 4.

Reference Type RESULT
PMID: 22560810 (View on PubMed)

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.

Reference Type RESULT
PMID: 21626077 (View on PubMed)

Hussein HM, Tariq NA, Palesch YY, Qureshi AI; ATACH Investigators. Reliability of hematoma volume measurement at local sites in a multicenter acute intracerebral hemorrhage clinical trial. Stroke. 2013 Jan;44(1):237-9. doi: 10.1161/STROKEAHA.112.667220. Epub 2012 Dec 11.

Reference Type DERIVED
PMID: 23233387 (View on PubMed)

Other Identifiers

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R01NS044976-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0609M93128

Identifier Type: -

Identifier Source: org_study_id