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Controlling Hyperadrenergic Activity in Neurologic Injury (CHAIN)

This study has been withdrawn prior to enrollment.
(Unable to enroll subjects that fit study criteria.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01343329
First Posted: April 28, 2011
Last Update Posted: April 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Wendy Ziai, Johns Hopkins University
  Purpose
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.

Condition Intervention Phase
Traumatic Brain Injury Dysautonomia Drug: Esmolol Drug: Propranolol Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Controlling Hyperadrenergic Activity in Neurologic Injury

Resource links provided by NLM:


Further study details as provided by Wendy Ziai, Johns Hopkins University:

Primary Outcome Measures:
  • 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


Enrollment: 0
Actual Study Start Date: July 2011
Study Completion Date: February 14, 2014
Primary Completion Date: February 14, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Inderal

  Eligibility

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01343329


Locations
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Wendy Ziai, MD Johns Hopkins University
  More Information

Additional Information:
Publications:

Responsible Party: Wendy Ziai, Associate Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01343329     History of Changes
Other Study ID Numbers: NA_00043058
First Submitted: April 26, 2011
First Posted: April 28, 2011
Last Update Posted: April 20, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Wendy Ziai, Johns Hopkins University:
Traumatic Brain Injury
Dysautonomia
Brain Injury
Sympathetic hyperactivity

Additional relevant MeSH terms:
Primary Dysautonomias
Autonomic Nervous System Diseases
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Propranolol
Esmolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Adrenergic beta-1 Receptor Antagonists