Working… Menu

Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients (AVP)

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. Identifier: NCT00795366
Recruitment Status : Completed
First Posted : November 21, 2008
Results First Posted : December 12, 2014
Last Update Posted : December 12, 2014
Information provided by (Responsible Party):
Kenneth Proctor, University of Miami

Brief Summary:

Traumatic brain injury (TBI) is among the leading causes of trauma death and disability in both civilian and military populations. The damage that occurs at the instant of trauma cannot be modified; the secondary injuries that occur afterward are the impediments to recovery and can be influenced by the physician. Cerebral ischemia is the most important secondary event that determines outcome following TBI. To minimize ischemic episodes once the patient has arrived at the hospital, most treatments are aimed at optimizing cerebral perfusion pressure (CPP). The cornerstones of these treatments include mannitol, to reduce intracranial pressure (ICP), and catecholamines, such as phenylephrine (PE), to increase mean arterial pressure (MAP), but these agents have undesired side effects. Nevertheless, once they lose potency, there are few alternatives. The main objective of this proposal to develop a new therapeutic option for CPP management in TBI patients using arginine vasopressin (AVP).

AVP is the endogenous anti-diuretic hormone. It is FDA-approved for use in the diagnosis and treatment of diabetes insipidus, for the prevention and treatment of post-operative abdominal distention, and in abdominal radiography to dispel interfering gas shadows. It has been used off-label for several other conditions. There is minimal information on its therapeutic potential after TBI. The investigators have demonstrated that AVP during fluid resuscitation rapidly restored hemodynamics, CPP, and improves acute survival in a clinically-relevant model of TBI. The investigators observed similar short term benefits after chest and liver trauma. Nevertheless, AVP has actions that could mask any short term benefit. The investigators have already defined risks and benefits of AVP therapy, relative to PE, in four different clinically-relevant laboratory model. The investigators now plan to evaluate this new therapy relative to the current evidence-based guideline for CPP management in TBI patients.

The working hypothesis is that the risk/benefit profile for AVP is equal, or superior to, PE at equi-effective doses for the management of CPP following TBI. A corollary is that a higher CPP can be safely tolerated with AVP vs catecholamines.

THE INVESTIGATORS AIM TO: Determine whether AVP is safe and effective to maintain CPP = 60 mm Hg in TBI patients.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: arginine vasopressin Drug: Standard catecholamine Not Applicable

Detailed Description:

This is a randomized, controlled, open-label clinical trial comparing vasopressin and catecholamines for cerebral perfusion pressure (CPP) control after a traumatic brain injury (TBI).

Once a neurosurgeon is consulted for a patient presenting with a TBI, they will review entry criteria and refer to study personnel to obtain informed consent.

After informed consent, subjects will be randomized into one of the 2 groups to receive either a catecholamine at the discretion of the attending physicians or vasopressin (AVP). A 6 hour dose of non-study drug will be permitted prior to initiation of study drug. The amount of study drug will be titrated to maintain cerebral perfusion pressure within normal limits. Subjects will be followed until they can maintain their CPP without vasopressor medication. Data collection will include amount and duration of vasopressor therapy and resulting cerebral perfusion pressure and time until successful weaning from vasopressor therapy.

All subsequent clinical care will be at the discretion of the attending physician.

The standard protocol/procedure for the discontinuation of drugs in each arm of the study is as follows: Vasopressors are discontinued in a step-wise fashion, regardless of the specific agent or the specific ICU patient population. In patients with severe traumatic brain injury (TBI), cerebral perfusion pressure (CPP) is maintained between 60 and 70 mmHg with vasopressors. When intracranial pressure (ICP) begins to correct (decrease), vasopressors are titrated downward slowly to maintain CPP. This continues until ICP is normalized and systemic hemodynamics are able to support a normal CPP. At this point, vasopressors are withdrawn completely. This process is standard regardless of the choice of vasopressor.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
Study Start Date : September 2008
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: AVP, arginine vasopressin
Drug: arginine vasopressin
Titrated to cerebral perfusion pressure greater than 60 mm Hg

Active Comparator: Standard Catecholamine
levophed, dopamine, phenylephrine)
Drug: Standard catecholamine
Titrated catecholamine of attending physicians preference to cerebral perfusion pressure greater than 60 mm Hg.

Primary Outcome Measures :
  1. Time ICP >20 [ Time Frame: The number of hours during the first 5 days of intracranial pressure monitoring ]
    The number of hours that participants remained with intracranial pressure above 20 mmHg

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age >/= 18 yrs,
  • Primary admission to the hospital within 8 h after injury
  • Closed head injury
  • Potential for intracranial pressure monitoring

Exclusion Criteria:

  • Pregnant or nursing women
  • Hemodynamic instability after initial resuscitation
  • Vasopressor therapy for greater than 6 hours

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 identifier (NCT number): NCT00795366

Layout table for location information
United States, Florida
Ryder Trauma Center
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Layout table for investigator information
Principal Investigator: Kenneth G Proctor, PhD University of Miami
Layout table for additonal information
Responsible Party: Kenneth Proctor, Professor, University of Miami Identifier: NCT00795366    
Other Study ID Numbers: 20060949
First Posted: November 21, 2008    Key Record Dates
Results First Posted: December 12, 2014
Last Update Posted: December 12, 2014
Last Verified: December 2014
Keywords provided by Kenneth Proctor, University of Miami:
TBI, trauma, brain
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Arginine Vasopressin
Vasoconstrictor Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs