Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)

Overview

About this study

The specific aims of this study are to:

Definitively determine the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of patients with death and disability (mRS 4-6) at 3 months among subjects with ICH who are treated within 4.5 hours of symptom onset.
Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the subjects' quality of life as measured by EuroQol at 3 months.
Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of hematoma expansion (defined as increase from baseline hematoma volume of > 33%) and in the change from baseline peri-hematoma volume at 24 hours on the serial computed tomographic (CT) scans.
Assess the safety of the intensive treatment relative to the standard treatment in the proportion of subjects with treatment-related serious adverse events (SAEs) within 72 hours.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Age 18 years or older
IV nicardipine can be initiated within 4.5 hours of symptom onset.
Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
Total GCS score (aggregate of verbal, eye, and motor response scores) of 5 or greater at time of ED arrival.
INR value < 1.5
CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement <60 cc.
For subjects randomized prior to IV antihypertensive administration: SBP greater than 180 mmHg* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT spontaneous SBP reduction to below 180 mmHg at the time of randomization OR
For subjects randomized after IV antihypertensive administration: SBP greater than 180 mmHg* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT SBP reduction to below 140 mmHg at the time of randomization.
Informed consent obtained by subject, legally authorized representative, or next of kin.
- Note: Patients with SBP < 180mmHg should be monitored for 4.5 hours from symptom onset as their SBP may rise to eligible levels before the eligibility window closes.

Exclusion Criteria:

ICH is due to previously known neoplasms, AVM, or aneurysms.
Intracerebral hematoma considered to be related to trauma.
ICH located in infratentorial regions such as pons or cerebellum.
IVH associated with intraparenchymal hemorrhage and blood completely fills one lateral ventricle or more than half of both ventricles.
Patient to receive immediate surgical evacuation.
Current pregnancy, or parturition within previous 30 days, or active lactation.
Use of dabigatran within the last 48 hours.
A platelet count less than 50,000mm3
Known sensitivity to nicardipine.
Pre-morbid disability requiring assistance in ambulation or activities of daily living.
Subject's living will precludes aggressive ICU management.
Subject is currently participating in another interventional clinical trial

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status
Jacksonville, Fla. Mayo Clinic principal investigator William Freeman, M.D.	Closed for enrollment

Mayo Clinic Location

Status

Jacksonville, Fla.

Mayo Clinic principal investigator

William Freeman, M.D.

Closed for enrollment

More information

Publications

Aggressive systolic blood pressure reduction may precipitate acute renal injury because of underlying hypertensive nephropathy in patients with intracerebral hemorrhage. The study's objective was to determine the rate and determinants of acute renal injury during acute hospitalization among subjects with intracerebral hemorrhage using a post hoc analysis of a multicenter prospective study. Read More on PubMed
The December 2003 report from the National Institute of Neurological Disorders and Stroke (NINDS) Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of blood pressure management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertensive response in ICH. To address important gaps in knowledge, we conducted a pilot study funded by the NINDS, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) I Trial, during 2004-2008 to determine the appropriate level of systolic blood pressure (SBP) reduction. We now have initiated a multi-center, randomized Phase III trial, the ATACH II Trial, to definitively determine the efficacy of early, intensive, antihypertensive treatment using intravenous (IV) nicardipine initiated within 3 h of onset of ICH and continued for the next 24 h in subjects with spontaneous supratentorial ICH. The primary hypothesis of this large (N = 1,280), streamlined, and focused trial is that SBP reduction to ≤140 mm Hg reduces the likelihood of death or disability at 3 months after ICH, defined by modified Rankin scale score of 4-6, by at least 10% absolute compared to standard SBP reduction to ≤180 mm Hg. The ATACH II trial is a natural extension of numerous case series, the subsequent ATACH I pilot trial, and a preliminary, randomized, and controlled trial in this patient population funded by the Australian National Health and Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 73% of the patients with acute ICH. The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP reduction. The ATACH II trial will have important public health implications by providing evidence of, or lack thereof, regarding the efficacy and safety of acute antihypertensive treatment in subjects with ICH. This treatment represents a strategy that can be made widely available without the need for specialized equipment and personnel, and therefore, can make a major impact upon clinical practice for treating patients with ICH. Read More on PubMed
Evidence indicates that systolic blood pressure (SBP) reduction may reduce hematoma expansion in patients with intracerebral hemorrhage (ICH) who are initially seen with acute hypertensive response. Read More on PubMed
To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorial intracerebral hemorrhage treated within 6 hrs after symptom onset. Read More on PubMed
This trial is a multicenter open-labeled pilot trial to determine the tolerability and safety of three escalating levels of antihypertensive treatment goals for acute hypertension in 60 subjects with supratentorial intracerebral hemorrhage (ICH). The pilot trial is the natural development of numerous case series evaluating the effect of antihypertensive treatment of acute hypertension in subjects with ICH. The proposed trial will have important public health implications by providing necessary information for a definitive phase III study regarding the efficacy of antihypertensive treatment of acute hypertension in subjects with ICH. The specific aims of the present pilot study are to: (1) Determine the tolerability of the treatment as assessed by achieving and maintaining three different systolic blood pressure goals with intravenous nicardipine infusion for 18 to 24 hours postictus in subjects with ICH who present within 6 hours of symptom onset; (2) Define the safety, assessed by the rate of neurological deterioration during treatment and serious adverse events, of three escalating systolic blood pressure treatment goals using intravenous nicardipine infusion; and (3) Obtain preliminary estimates of the treatment effect using the rate of hematoma expansion (within 24 hours) and modified Rankin scale and Barthel index at 3 months following symptom onset. Read More on PubMed

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