Controlling Hyperadrenergic Activity in Neurologic Injury (CHAIN)

April 18, 2017 updated by: Wendy Ziai, Johns Hopkins University
Traumatic brain injury (TBI) is frequently associated with a hyperadrenergic state accompanied by elevated levels of plasma catecholamines. In its more severe presentation, the hyperadrenergic state presents as dysautonomia, which is characterized by paroxysmal alteration in vital signs, including tachycardia. The investigators hypothesize that intravenous (IV) esmolol is as effective at controlling heart rate in hyperadrenergic states as oral propranolol, which is the standard of care. Our primary endpoint is efficacy of IV esmolol vs a PRN regimen of intermittent B-blockade in controlling heart rate below a pre-specified level (< 100 bpm) after Traumatic Brain Injury (TBI) or hemorrhagic neurologic injury. Heart rates will be recorded continuously as well as hourly.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

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
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital

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

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • TBI (Moderate/Severe TBI (GCS 12 or Head AIS>1) or hemorrhagic neurologic injury
  • Hyperadrenergic Activity: At least one paroxysmal episode (lasting at least 15 minutes) of Heart Rate 110 beats per minute during two or more consecutive days plus at least two more of the following that may not be better explained by another disease process (ex: sepsis):

Temperature of 38.5C Respiratory Rate 20 breaths per minute Agitation Diaphoresis Dystonia Stimulus responsive ("triggering of paroxysm")

- Informed Consent obtained

Exclusion Criteria:

  • Patients that do not meet criteria for dysautonomia (as stated above)
  • Age <18 years
  • Pregnancy
  • Hypotension - requiring pressor therapy to maintain baseline adequate CPP or mean arterial pressure
  • Cardiac arrhythmia - sinus bradycardia (HR <60), 2nd or 3rd degree AV block
  • Hemodynamic contraindications to intravenous beta-blockade such as a documented history of congestive heart failure (CHF), dependency on cardiac inotropes or documented bronchospastic disease
  • Any patient on chronic beta blockade as an outpatient.
  • Life expectancy < 48 hours or patients with "do not resuscitate orders"
  • Ongoing seizure activity
  • Informed consent not obtained

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Subjects Receiving Esmolol
The Esmolol arm is defined as a 48-hour intravenous infusion of esmolol (Brevibloc 20mg/ml), which will be started on enrollment.
Drug: Esmolol
The Esmolol arm is defined as a 48-hour intravenous infusion of esmolol (Brevibloc 20mg/ml), which will be started on enrollment. The infusion rate will begin at 50 micrograms/kg/min and be adjusted to achieve heart rates between 80 and 100 beats/min with standard dosing regimens used in our Neuro intensive care unit. The infusion will be started at a rate of 0.05 milligrams/kg/min (50 micrograms/kg/min) for 5 minutes. After the 5 minutes of initial infusion, maintenance infusion may be continued at 0.05 mg/kg/min or increased stepwise (e.g. 0.1 mg/kg/min, 0.15 mg/kg/min to a maximum of 0.2 mg/kg/min) with each step being maintained for 4 or more minutes until the target heart rate is achieved.
Other Names:
  • Brevibloc
Active Comparator: Subjects receiving Propranolol
The comparison arm will be comprised of oral propranolol, starting with 20mg PO every 6 hours prn (as needed) to reduce heart rate into target range. If 20mg is ineffective, the dose will be doubled at each dosing interval until an adequate dose is found, not to exceed 120mg four times daily. (ex: 20mg, 40mg, 80mg, 120mg)
Drug: Propranolol
The comparison arm will be comprised of oral propranolol, starting with 20mg PO every 6 hours prn (as needed) to reduce heart rate into target range. If 20mg is ineffective, the dose will be doubled at each dosing interval until an adequate dose is found, not to exceed 120mg four times daily. (ex: 20mg, 40mg, 80mg, 120mg)
Other Names:
  • Inderal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Controlling heart rate in traumatic brain injured patients
Time Frame: 72 hrs
Once the patient is randomized and start getting the study medication, we monitor heart rate and other vital signs for 72hrs
72 hrs

Collaborators and Investigators

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

Sponsor

Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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 (Actual)

July 1, 2011

Primary Completion (Actual)

February 14, 2014

Study Completion (Actual)

February 14, 2014

Study Registration Dates

First Submitted

April 26, 2011

First Submitted That Met QC Criteria

April 27, 2011

First Posted (Estimate)

April 28, 2011

Study Record Updates

Last Update Posted (Actual)

April 20, 2017

Last Update Submitted That Met QC Criteria

April 18, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA_00043058

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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