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

NCT00795366 | Completed Results

• 1 other identifier: 20060949
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury

Keywords

TBI, trauma, brain

Outcome Measures

Primary Outcomes (1)

• Time ICP >20

  The number of hours that participants remained with intracranial pressure above 20 mmHg

  The number of hours during the first 5 days of intracranial pressure monitoring

Study Arms (2)

AVP, arginine vasopressin

ACTIVE COMPARATOR

Vasopressin

Drug: arginine vasopressin

Standard Catecholamine

ACTIVE COMPARATOR

levophed, dopamine, phenylephrine)

Drug: Standard catecholamine

Interventions

arginine vasopressin DRUG

Titrated to cerebral perfusion pressure greater than 60 mm Hg

AVP, arginine vasopressin

Standard catecholamine DRUG

Titrated catecholamine of attending physicians preference to cerebral perfusion pressure greater than 60 mm Hg.

Standard Catecholamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

Ryder Trauma Center

Miami, Florida, 33136, United States

Location

Related Publications (4)

• Dudkiewicz M, Proctor KG. Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin. Crit Care Med. 2008 Sep;36(9):2641-50. doi: 10.1097/CCM.0b013e3181847af3.

  PMID: 18679110 BACKGROUND

• Sanui M, King DR, Feinstein AJ, Varon AJ, Cohn SM, Proctor KG. Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury. Crit Care Med. 2006 Feb;34(2):433-8. doi: 10.1097/01.ccm.0000196206.83534.39.

  PMID: 16424725 BACKGROUND

• Feinstein AJ, Cohn SM, King DR, Sanui M, Proctor KG. Early vasopressin improves short-term survival after pulmonary contusion. J Trauma. 2005 Oct;59(4):876-82; discussion 882-3. doi: 10.1097/01.ta.0000187654.24146.22.

  PMID: 16374276 BACKGROUND

• Feinstein AJ, Patel MB, Sanui M, Cohn SM, Majetschak M, Proctor KG. Resuscitation with pressors after traumatic brain injury. J Am Coll Surg. 2005 Oct;201(4):536-45. doi: 10.1016/j.jamcollsurg.2005.05.031.

  PMID: 16183491 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Wounds and Injuries

Interventions

Arginine Vasopressin

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System

Intervention Hierarchy (Ancestors)

Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Kenneth Proctor, PhD, Professor of Surgery
• Organization: University of Miami

kproctor@med.miami.edu

305-585-1178

Study Officials

• Kenneth G Proctor, PhD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 21, 2008
• Study Start: September 1, 2008
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: December 12, 2014
• Results First Posted: December 12, 2014

Record last verified: 2014-12

Locations

US (1)