Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients (AVP)
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|ClinicalTrials.gov Identifier: NCT00795366|
Recruitment Status : Completed
First Posted : November 21, 2008
Results First Posted : December 12, 2014
Last Update Posted : December 12, 2014
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||96 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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.
- 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
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): NCT00795366
|United States, Florida|
|Ryder Trauma Center|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Kenneth G Proctor, PhD||University of Miami|