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

Primary Purpose

Subarachnoid Hemorrhage

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Esmolol

About this trial

This is an interventional treatment trial for Subarachnoid Hemorrhage focused on measuring subarachnoid hemorrhage, esmolol, cardiac function, cardiac electrophysiology

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Michigan Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

esmolol

Standard care

Arm Description

Esmolol will be used preferentially to control hypertension.

Standard care for SAH includes other hypertensives such as nicardipine.

Outcomes

Primary Outcome Measures

Change in high sensitivity troponin

Secondary Outcome Measures

Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.

Proportion experiencing serious adverse event: hypotension requiring vasopressor (excluding during anesthesia), neurological deterioration, serious bronchospasm, and in hospital case fatality.

Disability (30 days +/-7).

Change in serum norepinephrine level from peak to nadir

Change in corrected QT interval

Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2

Proportion with electrocardiographic abnormalities cumulative through day 7

Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%

Proportion with life-threatening arrhythmias or cardiac arrest

Change in serum troponin and BNP levels from peak to nadir

Proportion with abnormal 30-day echocardiogram

Proportion with symptomatic cerebral vasospasm

Proportion with radiographic cerebral vasospasm

Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2)

Full Information

NCT ID

NCT01232400

First Posted

November 1, 2010

Last Updated

January 7, 2015

Sponsor

University of Michigan

1. Study Identification

Unique Protocol Identification Number

NCT01232400

Brief Title

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

Acronym

ABASH

Official Title

Adrenergic Blockade After Subarachnoid Hemorrhage

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Withdrawn

Why Stopped

Funding withdrawn. Design not feasible.

Study Start Date

July 2014 (undefined)

Primary Completion Date

July 2015 (Anticipated)

Study Completion Date

August 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Michigan

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Subarachnoid Hemorrhage

Keywords

subarachnoid hemorrhage, esmolol, cardiac function, cardiac electrophysiology

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

esmolol

Arm Type

Experimental

Arm Description

Esmolol will be used preferentially to control hypertension.

Arm Title

Standard care

Arm Type

No Intervention

Arm Description

Standard care for SAH includes other hypertensives such as nicardipine.

Intervention Type

Drug

Intervention Name(s)

Esmolol

Other Intervention Name(s)

Brevibloc

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in high sensitivity troponin

Time Frame

Peak to nadir within 7 days

Secondary Outcome Measure Information:

Title

Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.

Time Frame

Measured for 4 days from index SAH

Title

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

Title

Disability (30 days +/-7).

Time Frame

30 days from index SAH

Title

Change in serum norepinephrine level from peak to nadir

Time Frame

Baseline versus 4th day after index SAH

Title

Change in corrected QT interval

Time Frame

First week after presentation for index SAH

Title

Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2

Time Frame

First week after presentation.

Title

Proportion with electrocardiographic abnormalities cumulative through day 7

Time Frame

Baseline, and at first week after presentation.

Title

Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%

Time Frame

Baseline (within 24 hours of presentation for index SAH)

Title

Proportion with life-threatening arrhythmias or cardiac arrest

Time Frame

Measured through end of index hospitalization (approximately 30 days maximum)

Title

Change in serum troponin and BNP levels from peak to nadir

Time Frame

baseline through end of hospitalization

Title

Proportion with abnormal 30-day echocardiogram

Time Frame

30 days post index SAH

Title

Proportion with symptomatic cerebral vasospasm

Time Frame

baseline until end of hospitalization

Title

Proportion with radiographic cerebral vasospasm

Time Frame

baseline until end of hospitalization

Title

Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2)

Time Frame

5-7 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William J Meurer, MD, MS

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Health System

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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