Trial record 1 of 1 for:    NCT01176565
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Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)

This study is currently recruiting participants.
Verified November 2013 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborators:
Medical University of South Carolina
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01176565
First received: August 4, 2010
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

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.

Condition Intervention Phase
Intracerebral Hemorrhage
Drug: Nicardipine hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 1280
Study Start Date: January 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard SBP Reduction Arm
The goal for the standard BP reduction group will be to reduce and maintain SBP < 180 mmHg for 24 h from randomization. 180 mmHg is the target SBP for this arm.
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: Intensive SBP Reduction Arm
The goal for the intensive BP reduction group will be to reduce and maintain SBP < 140 mmHg for 24 h from randomization. 140 mmHg is the target SBP for this arm.
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01176565

Contacts
Contact: Adnan I Qureshi, MD 612-626-8221 qureshai@gmail.com

  Show 89 Study Locations
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Medical University of South Carolina
Investigators
Study Director: Yuko Y Palesch, Ph.D. Medical University of South Carolina
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01176565     History of Changes
Other Study ID Numbers: h
Study First Received: August 4, 2010
Last Updated: November 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Acute hypertensive response, intracerebral hemorrhage, blood pressure, outcome

Additional relevant MeSH terms:
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Nicardipine
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on April 22, 2014