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Study to Evaluate Esmolol (Brevibloc) to Manage Cardiac Function in Patients With Subarachnoid Hemorrhage (ABASH)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by University of Michigan
Sponsor:
Information provided by (Responsible Party):
William J Meurer, University of Michigan
ClinicalTrials.gov Identifier:
NCT01232400
First received: November 1, 2010
Last updated: May 19, 2014
Last verified: May 2014

November 1, 2010
May 19, 2014
July 2014
July 2015   (final data collection date for primary outcome measure)
Change in high sensitivity troponin [ Time Frame: Peak to nadir within 7 days ] [ Designated as safety issue: No ]
Change (baseline versus day 5) in systolic function measured by left ventricular ejection fraction. [ Time Frame: 5-7 days ] [ Designated as safety issue: No ]
LVEF will be measured quantitatively using Simpson's rule
Complete list of historical versions of study NCT01232400 on ClinicalTrials.gov Archive Site
  • Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg. [ Time Frame: Measured for 4 days from index SAH ] [ Designated as safety issue: No ]
  • Proportion experiencing serious adverse event: hypotension requiring vasopressor (excluding during anesthesia), neurological deterioration, serious bronchospasm, and in hospital case fatality. [ Time Frame: Measured during index hospitalization or first 30 days from index SAH ] [ Designated as safety issue: Yes ]
  • Disability (30 days +/-7). [ Time Frame: 30 days from index SAH ] [ Designated as safety issue: No ]
  • Change in serum norepinephrine level from peak to nadir [ Time Frame: Baseline versus 4th day after index SAH ] [ Designated as safety issue: No ]
  • Change in corrected QT interval [ Time Frame: First week after presentation for index SAH ] [ Designated as safety issue: No ]
  • Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2 [ Time Frame: First week after presentation. ] [ Designated as safety issue: No ]
  • Proportion with electrocardiographic abnormalities cumulative through day 7 [ Time Frame: Baseline, and at first week after presentation. ] [ Designated as safety issue: No ]
  • Proportion with depressed ejection fraction on initial echocardiogram 36 - 49% [ Time Frame: Baseline (within 24 hours of presentation for index SAH) ] [ Designated as safety issue: No ]
  • Proportion with life-threatening arrhythmias or cardiac arrest [ Time Frame: Measured through end of index hospitalization (approximately 30 days maximum) ] [ Designated as safety issue: Yes ]
  • Change in serum troponin and BNP levels from peak to nadir [ Time Frame: baseline through end of hospitalization ] [ Designated as safety issue: No ]
  • Proportion with abnormal 30-day echocardiogram [ Time Frame: 30 days post index SAH ] [ Designated as safety issue: No ]
  • Proportion with symptomatic cerebral vasospasm [ Time Frame: baseline until end of hospitalization ] [ Designated as safety issue: No ]
  • Proportion with radiographic cerebral vasospasm [ Time Frame: baseline until end of hospitalization ] [ Designated as safety issue: No ]
  • Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2) [ Time Frame: 5-7 days ] [ Designated as safety issue: No ]
  • Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg. [ Time Frame: Measured for 4 days from index SAH ] [ Designated as safety issue: No ]
  • Proportion experiencing serious adverse event: hypotension requiring vasopressor (excluding during anesthesia), neurological deterioration, serious bronchospasm, and in hospital case fatality. [ Time Frame: Measured during index hospitalization or first 30 days from index SAH ] [ Designated as safety issue: Yes ]
  • Disability (30-60 days). [ Time Frame: 30-60 days from index SAH ] [ Designated as safety issue: No ]
  • Change in serum norepinephrine level [ Time Frame: Baseline versus 4th day after index SAH ] [ Designated as safety issue: No ]
  • Change in corrected QT interval [ Time Frame: First week after presentation for index SAH ] [ Designated as safety issue: No ]
  • Proportion with echocardiographic wall motion abnormalities (Days 1-2 and 4-6) [ Time Frame: First week after presentation. ] [ Designated as safety issue: No ]
  • Proportion with electrocardiographic abnormalities (Days 5-6) [ Time Frame: Baseline, and at first week after presentation. ] [ Designated as safety issue: No ]
  • Proportion with depressed ejection fraction on initial echocardiogram [ Time Frame: Baseline (within 24 hours of presentation for index SAH) ] [ Designated as safety issue: No ]
  • Proportion with life-threatening arrhythmias [ Time Frame: Measured through end of index hospitalization (approximately 30 days maximum) ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study to Evaluate Esmolol (Brevibloc) to Manage Cardiac Function in Patients With Subarachnoid Hemorrhage
Adrenergic Blockade After Subarachnoid Hemorrhage

The purpose of this study is to evaluate the clinical effect of esmolol treatment on cardiac function and electrophysiology; to assess the effects of esmolol treatment on serum adrenergic and cardiac biomarkers; to explore the safety of esmolol treatment shortly after subarachnoid hemorrhage (SAH). Patients will be followed for a maximum of 1 month after the index SAH. The primary outcome will be change in systolic function - ejection fraction by Simpson's rule (baseline versus Day 7 +/- 2 after SAH).

Subarachnoid hemorrhage (SAH) remains one of the most devastating forms of stroke. Over 25% of all stroke related potential years of life lost are from SAH. Outcomes are adversely affected by secondary ischemia from cerebral vasospasm, along with cardiac complications. Trials performed in patients with SAH have demonstrated benefit after the administration of beta blockers - reducing mortality nearly in half; but concerns over diminishing cerebral perfusion inhibited the widespread adoption of this therapy. Our specific aims are as follows: 1. To evaluate the clinical effect of esmolol treatment on cardiac systolic and diastolic function, along with cardiac electrophysiology; 2. To assess the effects of esmolol treatment on serum adrenergic and cardiac biomarkers; 3. To explore the safety of esmolol shortly after SAH. The primary outcome will be change in systolic function - ejection fraction by Simpson's rule (baseline versus Day 7 +/- 2 after SAH).

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Subarachnoid Hemorrhage
Drug: Esmolol

The initial esmolol infusion will be 50 mcg/kg/minute IV. This will be increased by 25 mcg/kg/minute every 15 minutes until one of the following situations is reached:

  1. Heart rate less than 70 bpm.
  2. Systolic blood pressure less than 120 mmHg
  3. Maximum dose of esmolol of 200 mcg/kg/minute is reached.
Other Name: Brevibloc
  • Experimental: esmolol
    Esmolol will be used preferentially to control hypertension.
    Intervention: Drug: Esmolol
  • No Intervention: Standard care
    Standard care for SAH includes other hypertensives such as nicardipine.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
20
August 2016
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subarachnoid hemorrhage presumed to be the result of ruptured aneurysm
  • Age 18 years old or greater
  • Able to enroll within 24 hours of onset of symptoms
  • Systolic blood pressure over 140 mm Hg OR administration of antihypertensives after presentation

Exclusion Criteria:

  • Withdrawal of life support imminent (within six hours)
  • Known heart failure or cardiomyopathy AND ejection fraction 35% or below
  • Prisoner or pregnant female
  • Ongoing vasopressor administration to maintain SBP, or clinical suspicion of left ventricular failure
  • Clinically important arrhythmias (history of cardiac arrest or ventricular arrhythmias), conduction abnormalities (Mobitz Type 2, 3rd degree AV block, or symptomatic Mobitz 1 without pacemaker), clinical cardiogenic shock, or overt clinical heart failure
  • Active bronchospastic disease (ongoing bronchospasm after SAH presentation or current treatment with oral corticosteroids for asthma or obstructive lung disease)
  • End stage renal disease
Both
18 Years and older
No
Contact: William J Meurer, MD, MS 734-615-2766 wmeurer@umich.edu
Contact: Barbara Smith, BA, CCRP 734-936-4198 barsmith@umich.edu
United States
 
NCT01232400
HUM31297
Yes
William J Meurer, University of Michigan
University of Michigan
Not Provided
Principal Investigator: William J Meurer, MD, MS University of Michigan
University of Michigan
May 2014

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