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

January 7, 2015 updated by: William J Meurer, University of Michigan

Adrenergic Blockade After Subarachnoid Hemorrhage

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: esmolol
Esmolol will be used preferentially to control hypertension.
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 Names:
  • Brevibloc
NO_INTERVENTION: Standard care
Standard care for SAH includes other hypertensives such as nicardipine.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change in high sensitivity troponin
Time Frame: Peak to nadir within 7 days
Peak to nadir within 7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.
Time Frame: Measured for 4 days from index SAH
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.
Time Frame: Measured during index hospitalization or first 30 days from index SAH
Measured during index hospitalization or first 30 days from index SAH
Disability (30 days +/-7).
Time Frame: 30 days from index SAH
30 days from index SAH
Change in serum norepinephrine level from peak to nadir
Time Frame: Baseline versus 4th day after index SAH
Baseline versus 4th day after index SAH
Change in corrected QT interval
Time Frame: First week after presentation for index SAH
First week after presentation for index SAH
Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2
Time Frame: First week after presentation.
First week after presentation.
Proportion with electrocardiographic abnormalities cumulative through day 7
Time Frame: Baseline, and at first week after presentation.
Baseline, and at first week after presentation.
Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%
Time Frame: Baseline (within 24 hours of presentation for index SAH)
Baseline (within 24 hours of presentation for index SAH)
Proportion with life-threatening arrhythmias or cardiac arrest
Time Frame: Measured through end of index hospitalization (approximately 30 days maximum)
Measured through end of index hospitalization (approximately 30 days maximum)
Change in serum troponin and BNP levels from peak to nadir
Time Frame: baseline through end of hospitalization
baseline through end of hospitalization
Proportion with abnormal 30-day echocardiogram
Time Frame: 30 days post index SAH
30 days post index SAH
Proportion with symptomatic cerebral vasospasm
Time Frame: baseline until end of hospitalization
baseline until end of hospitalization
Proportion with radiographic cerebral vasospasm
Time Frame: baseline until end of hospitalization
baseline until end of hospitalization
Change in systolic function - ejection fraction by Simpson's rule (baseline vs Day 7 +/- 2)
Time Frame: 5-7 days
5-7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: William J Meurer, MD, MS, University of Michigan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2014

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 1, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2010

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 2, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HUM31297

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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