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AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock

AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01611935
Acronym
AVERTShock
Enrollment
101
Registered
2012-06-05
Start date
2013-05-01
Completion date
2016-09-06
Last updated
2019-05-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Traumatic Shock

Keywords

trauma, shock, vasopressin, blood transfusion

Brief summary

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.

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.

Interventions

DRUGVasopressin

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.

Sponsors

National Trauma Research Institute
CollaboratorOTHER
United States Department of Defense
CollaboratorFED
University of Pennsylvania
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Number of Blood Products Transfused48 hours following the initiation of therapyCumulative number of units of blood products, including packed red blood cells, plasma and platelets measured in liters

Secondary

MeasureTime frameDescription
Need for Vasopressor Requirement Vasopressor Requirement48 hours following the initiation of therapytotal 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
Total Number of Complications30 days post injuryVariables 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
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 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.
49
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. 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.
51
Total100

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyFamily Declined Participation10

Baseline characteristics

CharacteristicVasopressinTotalNormal Saline
Age, Continuous26 years26 years27 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Black or African American
42 Participants82 Participants40 Participants
Race (NIH/OMB)
More than one race
0 Participants2 Participants2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
7 Participants15 Participants8 Participants
Region of Enrollment
United States
49 participants100 participants51 participants
Sex: Female, Male
Female
3 Participants7 Participants4 Participants
Sex: Female, Male
Male
46 Participants93 Participants47 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
5 / 494 / 51
other
Total, other adverse events
22 / 4428 / 47
serious
Total, serious adverse events
30 / 4936 / 47

Outcome results

Primary

Number of Blood Products Transfused

Cumulative number of units of blood products, including packed red blood cells, plasma and platelets measured in liters

Time frame: 48 hours following the initiation of therapy

ArmMeasureValue (MEDIAN)
VasopressinNumber of Blood Products Transfused1.7 Litre
Normal SalineNumber of Blood Products Transfused3.0 Litre
Secondary

Need for Vasopressor Requirement Vasopressor Requirement

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

Time frame: 48 hours following the initiation of therapy

ArmMeasureValue (MEDIAN)
VasopressinNeed for Vasopressor Requirement Vasopressor Requirement0.6 Norepinephrine equivalents (g)
Normal SalineNeed for Vasopressor Requirement Vasopressor Requirement1.5 Norepinephrine equivalents (g)
Secondary

Total Number of Complications

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.

Time frame: 30 days post injury

Population: patients who did not survive the 48 hours were not included in the analysis

ArmMeasureValue (NUMBER)
VasopressinTotal Number of Complications69 Complications
Normal SalineTotal Number of Complications98 Complications

Source: ClinicalTrials.gov · Data processed: Feb 20, 2026