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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Kenneth Proctor, University of Miami
ClinicalTrials.gov Identifier:
NCT00795366
First received: November 20, 2008
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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 Intervention
Traumatic Brain Injury
Drug: arginine vasopressin
Drug: Standard catecholamine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Episodes of intracranial hypertension, hypoxemia, peripheral ischemia, urine output [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: September 2008
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AVP
Vasopressin
Drug: arginine vasopressin
Titrated to cerebral perfusion pressure greater than 60 mm Hg
Active Comparator: Catecholamine Drug: Standard catecholamine
Titrated catecholamine of attending physicians preference to cerebral perfusion pressure greater than 60 mm Hg.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00795366

Locations
United States, Florida
Ryder Trauma Center Recruiting
Miami, Florida, United States, 33136
Contact: Kenneth G Proctor, PhD       kproctor@med.miami.edu   
Contact: Carl I Schulman, MD, MSPH       cschulman@med.miami.edu   
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Kenneth G Proctor, PhD University of Miami
  More Information

Publications:
Responsible Party: Kenneth Proctor, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00795366     History of Changes
Other Study ID Numbers: 20060949
Study First Received: November 20, 2008
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
TBI, trauma, brain

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Arginine Vasopressin
Vasopressins
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014