Controlling Hyperadrenergic Activity in Neurologic Injury (CHAIN)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Johns Hopkins University.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01343329
First received: April 26, 2011
Last updated: April 27, 2011
Last verified: April 2011
  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). Heart rates will be recorded continuously as well as hourly.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Controlling Hyperadrenergic Activity in Neurologic Injury

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Controlling heart rate in traumatic brain injured patients [ Time Frame: 72 hrs ] [ Designated as safety issue: Yes ]
    Once the patient is randomized and start getting the study medication, we monitor heart rate and other vital signs for 72hrs


Estimated Enrollment: 34
Study Start Date: July 2011
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Esmolol arm
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: Comparison arm
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 prn
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • TBI (Moderate/Severe TBI (GCS 12 or Head AIS>1)
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01343329

Locations
United States, Maryland
Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Satish B Chandolu, MBBS, MHA    410-955-6488    satish@jhu.edu   
Contact: Elizabeth White, RN, CCRP    4105026367    ewhite11@jhmi.edu   
Principal Investigator: Wendy Ziai, MD         
Sponsors and Collaborators
Johns Hopkins University
  More Information

Additional Information:
Publications:

Responsible Party: Wendy Ziai, MD, Assistant Professor, Neuroanesthesiology and Critical Care, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01343329     History of Changes
Other Study ID Numbers: NA_00043058
Study First Received: April 26, 2011
Last Updated: April 27, 2011
Health Authority: United Sates: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on October 29, 2014