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Antihypertensive Treatment of Acute Cerebral Hemorrhage-II (ATACH-II)

This study has been terminated.
(Planned interim analysis: no significant outcome differences between groups)
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Medical University of South Carolina
Johns Hopkins University
University of Michigan
Neurocritical Care Research Network
National Cerebral and Cardiovascular Center
Japan Cardiovascular Research Foundation
Beijing Tiantan Hospital
China Medical University Hospital
University Hospital Heidelberg
Seoul National University Hospital
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01176565
First received: August 4, 2010
Last updated: September 30, 2016
Last verified: September 2016

August 4, 2010
September 30, 2016
May 2011
January 2016   (final data collection date for primary outcome measure)
A pragmatic, streamlined randomized design to evaluate the efficacy of intensive SBP reduction and its effect on outcomes measures at 24 h, 30 d and at 3 m from randomization in subjects with ICH [ Time Frame: August, 2010 through 3 + 1 months margin from final subject randomization ] [ Designated as safety issue: No ]
Primary outcome is death or disability, defined by modified Rankin scale (mRS) of 4-6 at 3 m following treatment. We chose the mRS because of its high inter-observer reliability, superiority to other indices (e.g., Barthel index), and consistency with previous trials in patients with ICH. Further reliability will be increased by training raters in using the structured interview and obtaining a mRS grade. A dichotomous outcome was chosen to reduce the rate of mis-classification and increase the sensitivity of detecting meaningful difference.
A pragmatic, streamlined randomized design to evaluate the efficacy of intensive SBP reduction and its effect on outcomes measures at 24 h and at 3 m from randomization in subjects with ICH [ Time Frame: August, 2010- July 2015 ] [ Designated as safety issue: No ]
Primary outcome is death or disability, defined by modified Rankin scale (mRS) of 4-6 at 3 m following treatment. We chose the mRS because of its high inter-observer reliability, superiority to other indices (e.g., Barthel index), and consistency with previous trials in patients with ICH. Further reliability will be increased by training raters in using the structured interview and obtaining a mRS grade. A dichotomous outcome was chosen to reduce the rate of misclassification and increase the sensitivity of detecting meaningful difference.
Complete list of historical versions of study NCT01176565 on ClinicalTrials.gov Archive Site
  • Secondary outcomes [ Time Frame: August, 2010 through 3 + 1 months margin from final subject randomization ] [ Designated as safety issue: No ]
    EuroQOL: EuroQOL (EQ) is a simple, standardized non-disease-specific instrument for describing and valuating health-related quality of life. Its components are a printed 'thermometer'-type visual analogue scale and EQ-5D, which consists of 5 questions in 5 different domains and allows for responses from 1 (the best outcome) to 3 (the worst).
  • Secondary Outcomes [ Time Frame: August, 2010 though 3 + 1 months margin from final hospital discharge of any subject enrolled. ] [ Designated as safety issue: Yes ]
    Hematoma expansion as determined by serial CT scans: Hematoma expansion will be defined as an increase in the volume of intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-h CT compared with the baseline CT scan.
Secondary Outcomes [ Time Frame: August, 2010- July 2015 ] [ Designated as safety issue: No ]

EuroQOL: EuroQOL, is a simple, standardized non-disease-specific instrument for describing and valuating health-related quality of life. Its components are a printed 'thermometer'-type visual analogue scale and EQ-5D, which consists of 5 questions in 5 different domains and allows for responses from 1 (the best outcome) to 3 (the worst).

Hematoma expansion as determined by serial CT scans: Hematoma expansion will be defined as an increase in the volume of intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-h CT compared with the baseline CT scan.

Not Provided
Not Provided
 
Antihypertensive Treatment of Acute Cerebral Hemorrhage-II
Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-II: A Phase III Randomized Multicenter Clinical Trial of Blood Pressure Reduction for Hypertension in Acute Intracerebral Hemorrhage

The specific aims of this study are to:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
The report from a National Institute of Neurological Disorders and Stroke Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) in December 2003 recommended clinical trials for evaluation of blood pressure (BP) 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 hypertension in ICH. Consequently, we propose to conduct a five-year international, multicenter, open-labeled, randomized, controlled, Phase III trial to determine the efficacy of early, intensive antihypertensive treatment using intravenous nicardipine for acute hypertension in subjects with co-morbid hypertension and spontaneous supratentorial ICH. The primary hypothesis of this large, streamlined, focused trial is that the group treated with intensive BP reduction (systolic BP [SBP] of 140 mmHg or less - hereafter referred to as the intensive treatment) using intravenous nicardipine infusion for 24 hours reduces the proportion of death and disability at 3 months by 10% or greater compared with the group treated with the standard BP reduction (SBP of 180 mmHg or less - hereafter referred to as the standard treatment) among patients with ICH treated within 4.5 hours of symptom onset. The underlying mechanism for this expected beneficial effect of intensive treatment is mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 38% of patients with acute ICH. The trial will recruit a maximum of 1,280 subjects with ICH who meet the eligibility criteria. The primary outcome is the proportion of death and disability at 3 months defined by modified Rankin scale (mRS) score of 4 to 6. The proposed clinical trial is the natural extension of numerous case series, a subsequent pilot trial funded by the National Institutes of Health National Institute of Health (NIH), and a preliminary randomized controlled trial in this patient group funded by the Australian National Health and Medical Research Council, that have recently confirmed the safety and tolerability of both the regimen and goals of the antihypertensive treatment in acutely hypertensive patients with ICH proposed in the present trial. The proposed trial will have important public health implications by providing necessary information regarding the efficacy and safety of antihypertensive treatment of acute hypertension observed in up to 75% of the subjects with ICH. BP treatment represents a strategy that can be made widely available without the need of specialized equipment and personnel and therefore can make a major impact upon outcome in patients with ICH. Substantial reduction in morbidity and mortality appears possible if the estimates of treatment effect sizes from our current pilot trials are accurate.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Intracerebral Hemorrhage
Drug: Nicardipine hydrochloride
IV nicardipine will be initiated at a rate of 5 mg/hr and increased by 2.5 mg/hr increments will continue every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is > target SBP despite infusion of the maximum nicardipine dose for 30 min, a second agent can be used (Labetalol 5-20 mg IV bolus every 15 min) for another h.
Other Name: Cardene® I.V.
  • Active Comparator: Standard SBP Reduction Arm

    Nicardipine hydrochloride will be used PRN as primary agent in lowering SBP.

    The goal for the standard BP reduction group will be to reduce and maintain SBP < 180 mmHg for 24 h from randomization. 160 mmHg is the target SBP for this arm.

    Intervention: Drug: Nicardipine hydrochloride
  • Active Comparator: Intensive SBP Reduction Arm

    Nicardipine hydrochloride will be used PRN as primary agent in lowering SBP.

    The goal for the intensive BP reduction group will be to reduce and maintain SBP < 140 mmHg for 24 h from randomization. 125 mmHg is the target SBP for this arm.

    Intervention: Drug: Nicardipine hydrochloride

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1000
March 2016
January 2016   (final data collection date for primary outcome measure)

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 Glasgow Coma Scale (GCS) score (aggregate of verbal, eye, and motor response scores) of 5 or greater at time of emergency department (ED) arrival.
  • International normalized ratio (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, arteriovenous malformation (AVM), or aneurysms.
  • Intracerebral hematoma considered to be related to trauma.
  • ICH located in infratentorial regions such as pons or cerebellum.
  • Intraventricular hemorrhage (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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   China,   Germany,   Japan,   Korea, Republic of,   Taiwan
 
NCT01176565
1207M17921, U01NS062091, U01NS061861
Yes
Yes
A public use data set from the study database will be made available. A process for sharing subject head imaging studies that may be associated with the data set is under evaluation.
University of Minnesota - Clinical and Translational Science Institute
University of Minnesota - Clinical and Translational Science Institute
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Medical University of South Carolina
  • Johns Hopkins University
  • University of Michigan
  • Neurocritical Care Research Network
  • National Cerebral and Cardiovascular Center
  • Japan Cardiovascular Research Foundation
  • Beijing Tiantan Hospital
  • China Medical University Hospital
  • University Hospital Heidelberg
  • Seoul National University Hospital
Study Chair: Adnan I Qureshi, MD University of Minnesota - Clinical and Translational Science Institute
Study Director: Yuko Y Palesch, PhD Medical University of South Carolina
Principal Investigator: Adnan I Qureshi, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Yuko Y Palesch, PhD Medical University of South Carolina
University of Minnesota - Clinical and Translational Science Institute
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP