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

Not Applicable
Withdrawn
Conditions
Subarachnoid Hemorrhage
Interventions
Registration Number
NCT01232400
Lead Sponsor
University of Michigan
Brief Summary

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).

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).

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
esmololEsmololEsmolol will be used preferentially to control hypertension.
Primary Outcome Measures
NameTimeMethod
Change in high sensitivity troponinPeak to nadir within 7 days
Secondary Outcome Measures
NameTimeMethod
Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%Baseline (within 24 hours of presentation for index SAH)
Proportion with life-threatening arrhythmias or cardiac arrestMeasured through end of index hospitalization (approximately 30 days maximum)
Proportion with abnormal 30-day echocardiogram30 days post index SAH
Proportion with symptomatic cerebral vasospasmbaseline until end of hospitalization
Proportion with radiographic cerebral vasospasmbaseline until end of hospitalization
Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2)5-7 days
Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.Measured for 4 days from index SAH
Proportion experiencing serious adverse event: hypotension requiring vasopressor (excluding during anesthesia), neurological deterioration, serious bronchospasm, and in hospital case fatality.Measured during index hospitalization or first 30 days from index SAH
Disability (30 days +/-7).30 days from index SAH
Change in serum norepinephrine level from peak to nadirBaseline versus 4th day after index SAH
Change in corrected QT intervalFirst week after presentation for index SAH
Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2First week after presentation.
Proportion with electrocardiographic abnormalities cumulative through day 7Baseline, and at first week after presentation.
Change in serum troponin and BNP levels from peak to nadirbaseline through end of hospitalization

Trial Locations

Locations (1)

University of Michigan Health System

🇺🇸

Ann Arbor, Michigan, United States

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