Clinical trial NCT00415610: Antihypertensive Treatment in Acute Cerebral Hemorrhage
Official title: Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Intracerebral Hemorrhage
Hypertension
Stroke
Keywords: cerebral hemorrhage
intracerebral hemorrhage
stroke
hypertension
blood pressure
nicardipine
antihypertensive agent
hematoma expansion
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2006-12-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 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 purpose: TREATMENT

Brief summary: 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: 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 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.

Primary outcomes:
measure: Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.
timeFrame: Within 3 hours of symptom onset and sustained through 18-24 hours.
measure: Number of Participants With Neurological Deteriorations (Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score) During the 24 Hour Treatment",
timeFrame: within the first 72 hours of treatment initiation
measure: Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject
timeFrame: from treatment initiation through 72 hours
Secondary outcomes:
measure: Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals
timeFrame: 3 months
Other outcomes:
measure: Particpants Who 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 Resulting in Death.
timeFrame: From enrollment through 3 months
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General/Brigham Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Clinical Coordinating Center: University of Minnesota, Fairview Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Charleston
country: United States
facility: Statistical Coordinating Center: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: University of Minnesota
name: Adnan I. Qureshi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.