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

This study is not yet open for participant recruitment.
Verified December 2013 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: December 10, 2013
Last verified: December 2013
  Purpose

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).


Condition Intervention
Subarachnoid Hemorrhage
Drug: Esmolol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adrenergic Blockade After Subarachnoid Hemorrhage

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • 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 ]
    LVEF will be measured quantitatively using Simpson's rule


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: esmolol 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
No Intervention: Standard care
The esmolol treated group will be compared to a group that receives standard care for SAH.

Detailed Description:

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).

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01232400

Contacts
Contact: William J Meurer, MD, MS 734-615-2766 wmeurer@umich.edu
Contact: Barbara Smith, BA, CCRP 734-936-4198 barsmith@umich.edu

Locations
United States, Michigan
University of Michigan Health System Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: William J Meurer, MD, MS    734-936-1616    wmeurer@med.umich.edu   
Principal Investigator: William J Meurer, MD, MS         
Sub-Investigator: Venkatakrishna Rajajee, MD         
Sub-Investigator: Aditya Pandey, MD         
Sub-Investigator: Mark Benson, MD         
Sub-Investigator: B. Gregory Thompson, MD         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: William J Meurer, MD, MS University of Michigan
  More Information

No publications provided

Responsible Party: William J Meurer, Assistant Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01232400     History of Changes
Other Study ID Numbers: HUM31297
Study First Received: November 1, 2010
Last Updated: December 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
subarachnoid hemorrhage
esmolol
cardiac function
cardiac electrophysiology

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Esmolol
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014