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

Subarachnoid Hemorrhage Clinical Trial

— ABASH  

Official title:

Adrenergic Blockade After Subarachnoid Hemorrhage

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01232400
• Other study ID #: HUM31297
• Status: Withdrawn
• Phase: N/A
• First received: November 1, 2010
• Last updated: January 7, 2015
• Start date: July 2014
• Est. completion date: August 2016

Study information

• Verified date: January 2015
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage

Intervention

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: Heart rate less than 70 bpm. Systolic blood pressure less than 120 mmHg Maximum dose of esmolol of 200 mcg/kg/minute is reached.

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in high sensitivity troponin		Peak to nadir within 7 days	No
Secondary	Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.		Measured for 4 days from index SAH	No
Secondary	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	Yes
Secondary	Disability (30 days +/-7).		30 days from index SAH	No
Secondary	Change in serum norepinephrine level from peak to nadir		Baseline versus 4th day after index SAH	No
Secondary	Change in corrected QT interval		First week after presentation for index SAH	No
Secondary	Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2		First week after presentation.	No
Secondary	Proportion with electrocardiographic abnormalities cumulative through day 7		Baseline, and at first week after presentation.	No
Secondary	Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%		Baseline (within 24 hours of presentation for index SAH)	No
Secondary	Proportion with life-threatening arrhythmias or cardiac arrest		Measured through end of index hospitalization (approximately 30 days maximum)	Yes
Secondary	Change in serum troponin and BNP levels from peak to nadir		baseline through end of hospitalization	No
Secondary	Proportion with abnormal 30-day echocardiogram		30 days post index SAH	No
Secondary	Proportion with symptomatic cerebral vasospasm		baseline until end of hospitalization	No
Secondary	Proportion with radiographic cerebral vasospasm		baseline until end of hospitalization	No
Secondary	Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2)		5-7 days	No