Clinical trial NCT01232400: Study to Evaluate Esmolol (Brevibloc) to Manage Cardiac Function in Patients With Subarachnoid Hemorrhage
Official title: Adrenergic Blockade After Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Subarachnoid Hemorrhage
Keywords: subarachnoid hemorrhage
esmolol
cardiac function
cardiac electrophysiology
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2010-11-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Change in high sensitivity troponin
timeFrame: Peak to nadir within 7 days
Secondary outcomes:
measure: Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.
timeFrame: Measured for 4 days from index SAH
measure: Proportion experiencing serious adverse event: hypotension requiring vasopressor (excluding during anesthesia), neurological deterioration, serious bronchospasm, and in hospital case fatality.
timeFrame: Measured during index hospitalization or first 30 days from index SAH
measure: Disability (30 days +/-7).
timeFrame: 30 days from index SAH
measure: Change in serum norepinephrine level from peak to nadir
timeFrame: Baseline versus 4th day after index SAH
measure: Change in corrected QT interval
timeFrame: First week after presentation for index SAH
measure: Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2
timeFrame: First week after presentation.
measure: Proportion with electrocardiographic abnormalities cumulative through day 7
timeFrame: Baseline, and at first week after presentation.
measure: Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%
timeFrame: Baseline (within 24 hours of presentation for index SAH)
measure: Proportion with life-threatening arrhythmias or cardiac arrest
timeFrame: Measured through end of index hospitalization (approximately 30 days maximum)
measure: Change in serum troponin and BNP levels from peak to nadir
timeFrame: baseline through end of hospitalization
measure: Proportion with abnormal 30-day echocardiogram
timeFrame: 30 days post index SAH
measure: Proportion with symptomatic cerebral vasospasm
timeFrame: baseline until end of hospitalization
measure: Proportion with radiographic cerebral vasospasm
timeFrame: baseline until end of hospitalization
measure: Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2)
timeFrame: 5-7 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: University of Michigan
name: William J Meurer, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: