AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock (AVERTShock)

April 30, 2019 updated by: University of Pennsylvania
Trauma patients, who are transfused with multiple blood products to treat shock due to blood loss, frequently develop inappropriately low vasopressin levels. Vasopressin is a hormone necessary to maintain an adequate blood pressure and low levels have been associated with the need for increased transfusions, vasopressors and additional morbidity. Vasopressin is routinely used in the ICU to treat septic shock and other disease processes resulting in decreased vasopressin levels and low blood pressure. This study will investigate the potential benefit of early vasopressin supplementation during the resuscitation of trauma patients and the applicability of using copeptin as a vasopressin biomarker. Trauma patients who receive 6 or more units of blood product within 12 hours of arrival will be randomized to receive a vasopressin bolus plus infusion or a similar volume of a placebo (normal saline) for 48 hours. Serial blood samples will be taken for 5 days post-injury. Clinical and demographic data will be recorded prospectively.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Trauma remains the leading cause of death for those under the age of 40 in the United States, with a large percentage of patients dying from blood loss within the initial post-injury hours. Although resuscitation with intravenous fluids and blood products has remained the gold standard over the last twenty years, vigorous volume resuscitation may not be curative and has been associated with the development of serious complications including coagulopathy, acute lung injury, and abdominal compartment syndrome. Massive resuscitation also profoundly alters the neuroendocrine milieu needed to maintain vasomotor tone and these severely injured patients may progress to a state of recalcitrant hypotension, multi-organ failure, and ultimately death. The inclusion of vasoactive hormones during resuscitation could potentially prevent the profound hypotension seen in late stage shock, limit the need for aggressive volume and blood product resuscitation, and decrease the incidence of resuscitation-associated complications. As such, there exists an urgent need to evaluate novel resuscitation strategies that target neuroendocrine deficiencies in hemorrhagic shock. The hormone arginine vasopressin (AVP), in particular, may prove a useful adjunct during resuscitation. Secreted by the posterior pituitary, vasopressin is essential for maintaining vasomotor tone during hemorrhagic shock and low levels are associated with the development of catecholamine-resistant hypotension and profound venodilation. Trauma patients who require more than 5 units of blood products during their initial resuscitation are at risk for developing a vasopressin insufficiency, the need for vasopressor support, and often require longer ICU stays. Vasopressin has enjoyed widespread off-label use as a vasopressor in cardiac arrest, septic shock, and post-cardiopulmonary vasodilatory shock. The central hypothesis is that trauma patients who present in hemorrhagic shock are at risk for vasopressin deficiency and would benefit from early vasopressin supplementation. This study will investigate if early use of vasopressin during the resuscitation of traumatic shock results in fewer blood transfusions, a decreased need for crystalloid resuscitation, and a lower incidence of resuscitation related complications.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
101

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital at the Unversity of Pennyslvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Trauma patients between the ages of 18 and 65 who require 6 or more units of blood product during their initial 12 hours of resuscitation will be considered for enrollment.

Exclusion Criteria:

  • Patients with a traumatic brain injury requiring neurosurgical operative intervention or who have neurologic trauma deemed non-survivable will also be excluded.
  • Patients with an active coronary syndrome, history of myocardial infarction or coronary artery disease will be excluded.
  • Patients with known renal dysfunction requiring dialysis will be excluded.
  • Patients who are pregnant will be excluded.
  • Patients less than 18 years old will be excluded.
  • Patients who have opted out by bracelet identification or by listing themselves on the "Non-Participant" roster.
  • Patients under the jurisdiction of the department of corrections and considered prisoners prior to the initiation of the research intervention will be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Vasopressin
Vasopressin will be given as an initial bolus (4 Units) followed by an infusion titrated between 0 units/min to 0.04 units per min to maintain a mean arterial blood pressure greater than or equal to 65 mmHg
Drug: Vasopressin
After receiving greater than 6 units of blood product within the first 12 hours of admission, trauma patients will be randomized to either normal saline or vasopressin. Subjects will receive an initial 4 unit bolus followed by an infusion of 0 to 0.04 units titrated to maintain a mean arterial blood pressure of equal to or greater than 65 mmHg for a total of 48 hours.
Placebo Comparator: Normal Saline
An initial bolus of normal saline will be given (10 cc) and an infusion of 0.1 ml per minute will be started and titrated down in as the mean arterial blood pressure reaches 65 mmHg or more.
Drug: Vasopressin
After receiving greater than 6 units of blood product within the first 12 hours of admission, trauma patients will be randomized to either normal saline or vasopressin. Subjects will receive an initial 4 unit bolus followed by an infusion of 0 to 0.04 units titrated to maintain a mean arterial blood pressure of equal to or greater than 65 mmHg for a total of 48 hours.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Blood Products Transfused
Time Frame: 48 hours following the initiation of therapy
Cumulative number of units of blood products, including packed red blood cells, plasma and platelets measured in liters
48 hours following the initiation of therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Need for Vasopressor Requirement Vasopressor Requirement
Time Frame: 48 hours following the initiation of therapy
total dose of vasopressors (epinephrine, norepinephrine, neosynephrine, etc) received by patient within 48 hours converted to norepinephrine equivalents (g) range in our study was from 0 gm to a max of 53 gm
48 hours following the initiation of therapy
Total Number of Complications
Time Frame: 30 days post injury
Variables will include intra-abdominal hypertension, open abdomen free days, ventilator-free days, ICU-free days, development of ARDS, development of renal failure, development of multiple organ failure, volume of crystalloid requirement within 48 hours post injury, and mortality.
30 days post injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
United States Department of Defense
National Trauma Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carrie A Sims, MD, MS, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 6, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 6, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 1, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 5, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 21, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 811293

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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