Controlling Hyperadrenergic Activity in Neurologic Injury (CHAIN)
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ClinicalTrials.gov Identifier: NCT01343329 |
Recruitment Status :
Withdrawn
(Unable to enroll subjects that fit study criteria.)
First Posted : April 28, 2011
Last Update Posted : April 20, 2017
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Condition or disease | Intervention/treatment | Phase |
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Traumatic Brain Injury Dysautonomia | Drug: Esmolol Drug: Propranolol | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 0 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Controlling Hyperadrenergic Activity in Neurologic Injury |
Actual Study Start Date : | July 2011 |
Actual Primary Completion Date : | February 14, 2014 |
Actual Study Completion Date : | February 14, 2014 |

Arm | Intervention/treatment |
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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.
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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)
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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 |
- 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

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

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
United States, Maryland | |
Johns Hopkins Hospital | |
Baltimore, Maryland, United States, 21287 |
Principal Investigator: | Wendy Ziai, MD | Johns Hopkins University |
Publications:
Responsible Party: | Wendy Ziai, Associate Professor, Johns Hopkins University |
ClinicalTrials.gov Identifier: | NCT01343329 |
Other Study ID Numbers: |
NA_00043058 |
First Posted: | April 28, 2011 Key Record Dates |
Last Update Posted: | April 20, 2017 |
Last Verified: | April 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Traumatic Brain Injury Dysautonomia Brain Injury Sympathetic hyperactivity |
Brain Injuries Brain Injuries, Traumatic Primary Dysautonomias Autonomic Nervous System Diseases Wounds and Injuries 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 |