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Trial record 3 of 6 for:    "Brain Injury" | "Norepinephrine"

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

Tracking Information
First Submitted Date  ICMJE November 20, 2008
First Posted Date  ICMJE November 21, 2008
Results First Submitted Date  ICMJE December 1, 2014
Results First Posted Date  ICMJE December 12, 2014
Last Update Posted Date December 12, 2014
Study Start Date  ICMJE September 2008
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2014)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2008)
Episodes of intracranial hypertension [ Time Frame: At discharge ]
Change History Complete list of historical versions of study NCT00795366 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
Official Title  ICMJE Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Traumatic Brain Injury
Intervention  ICMJE
  • Drug: arginine vasopressin
    Titrated to cerebral perfusion pressure greater than 60 mm Hg
  • Drug: Standard catecholamine
    Titrated catecholamine of attending physicians preference to cerebral perfusion pressure greater than 60 mm Hg.
Study Arms  ICMJE
  • Active Comparator: AVP, arginine vasopressin
    Intervention: Drug: arginine vasopressin
  • Active Comparator: Standard Catecholamine
    levophed, dopamine, phenylephrine)
    Intervention: Drug: Standard catecholamine
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 11, 2014)
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2008)
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00795366
Other Study ID Numbers  ICMJE 20060949
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kenneth Proctor, University of Miami
Study Sponsor  ICMJE University of Miami
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kenneth G Proctor, PhD University of Miami
PRS Account University of Miami
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP