Controlling Hyperadrenergic Activity in Neurologic Injury

Phase 1

Withdrawn

• Conditions: Dysautonomia; Traumatic Brain Injury
• Interventions: Drug: Esmolol; Drug: Propranolol

• Registration Number: NCT01343329
• Lead Sponsor: Johns Hopkins University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-04-26
• Study First Submitted QC: 2011-04-27
• Study First Posted: 2011-04-28
• Study Start: 2011-07
• Primary Completion: 2014-02-14
• Study Completion: 2014-02-14
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-18
• Last Update Posted: 2017-04-20

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Subjects Receiving Esmolol	Esmolol	The Esmolol arm is defined as a 48-hour intravenous infusion of esmolol (Brevibloc 20mg/ml), which will be started on enrollment.
Subjects receiving Propranolol	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)

Primary Outcome Measures

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

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States