Stroke Trials Registry

ATACH
Antihypertensive Treatment in Acute Cerebral Hemorrhage

Principal Investigator
Adnan I. Qureshi, MD

PI Address
Adnan I. Qureshi, MD
Executive Director, Stroke Center
Associate Head
Department of Neurology
Professor of Neurology, Neurosurgery, and Radiology
University of Minnesota
12-100 PWB
516 Delware St. SE
Minneapolis, MN 55455
Email: aiqureshi@hotmail.com

Contact Address
Jill M. Novitzke, RN
Zeenat Qureshi Stroke
Research Center
University of Minnesota
Department of Neurology
12-131 PWB
516 Delaware St SE
Minneapolis, MN 55455

PH 612/626-9302

FX 612/625-7950

Email: novit001@umn.edu

Contact Email
novit001@umn.edu

Sponsor

Trial Phase:	Phase I
Study Size Actual:	60
Study Size Planned:	60
Centers Actual:	12
Centers Planned:	9
Max Time from onset:	12 Hours
Min Age:	18
Follow-up Duration:	3 Months
ISRCTN#	NCT00415610

Status:
Recruitment completed in August 2007. Results are currently in press awating publication. A proposed Phase III clinical trial ATACH-2. ATACH-2 is a five-year international, multicenter, open-labeled, randomized, controlled trial to determine the efficacy of early, intensive antihypertensive treatment using IV nicarpidine for subjects with co-morbid hypertension and spontaneoud ICH.

Purpose:
To evaluate the treatment feasibility and safety of three escalating levels of antihypertensive treatment in subjects with acute hypertension associated with intracerebral hemorrhage.

Interventions:

Nicardipine
Calcium channel blocker.

Location(s):
University of Minnesota
University of Medicine and Dentistry of New Jersey
St. Louis University
Via Christi Medical Center
Massachusetts General Hospital
Case Western Reserve University
Ohio State University
JFK Medical center-NJ Neuroscience Institute
Kansas University Medical Center
University of Southern California

Year Started: 2006

Year Finished: 2007

Year Presented: 2010

Year Published: 2007

Design:
Interventional, Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study.

Inclusion Criteria
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.

Patient Involvement:
Step-wise, interventional design. Enrolled patients will be administered anti-hypertensive treatment to reduce systolic blood pressure to 170-200 mm Hg. Following success of this, patients will be graduated to the next two levels of blood pressure reduction (140-170 mm Hg and 110-140 mm Hg). Institutional DSMB approval will be required to move patients to the next level.

Primary Outcome:
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.

Secondary Outcome:
Safety, as determined by the amount of neurological deteriorations during the 24 hour treatment period, plus the number of serious adverse events

Results:
A total of 60 patients were recruited (aged 62+/-15.1 years; 56.7% were men) with 18, 20, and 22 patients
recruited in each of the tiers of blood pressure reduction of increasing intensity. The mean time interval between symptom onset and presentation to the hospital was 1.8+/-1.4 hours and mean time to initiation of study treatment was 4.2+/-1.7 hours. Primary treatment failure was observed in 6 of 60 patients, all in the last tier. A total of 3 secondary treatment failures were observed, all in the third tier. Overall, a total of 9 of 60 patients had primary or secondary
treatment failures. The safety stopping rule was not activated in any of the tiers. Seven neurological deteriorations were observed: 1, 2, and 4 in the first, second, and third tier, respectively. These were related to hematoma expansion (n=6) and hydrocephalus (n=1). The
three month mortality ranged from 10% to 22% between the tiers. The age, initial GCS score, hematoma volume and intraventricular extension adjusted mortality did not differ between the three tiers. The age, initial GCS score, hematoma volume and intraventricular extension adjusted three month favorable outcome did not differ between the three tiers. In conclusion, aggressive SBP reduction to 110–140 mm Hg in the first 24 hours using intravenous
nicardipine was well tolerated with a low risk of hematoma expansion, neurological deterioration and in-hospital mortality. The results favor pharmacological reduction of SBP in patients with acute ICH.

Source of Information:
Presented at the 2005 International Stroke Conference (February 2005).
Presented at the 2006 International Stroke Conference [Februrary 2006].
Presented at the 2008 International Stroke Conference [Februrary 2008].
Presented at the 2009 International Stroke Conference [Februrary 2009].
Presented at the 2010 International Stroke Conference [Februrary 2010].

Web Links and Publications:

Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design.
Neurocrit Care 2007;6(1):56-66

ATACH-II
StrokeCenter.org

ATACH
ClinicalTrials.gov

This information last updated on: 6/25/2010

Reviewed on: 09/15/2009.

UID: 602