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

NCT ID: NCT01611935

Last Updated: 2019-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-01
• Study Completion Date: 2016-09-06

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.

Conditions

Traumatic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Vasopressin

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Vasopressin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Trauma Research Institute

OTHER

Sponsor Role: collaborator

United States Department of Defense

FED

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carrie A Sims, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Hospital at the Unversity of Pennyslvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Sims CA, Holena D, Kim P, Pascual J, Smith B, Martin N, Seamon M, Shiroff A, Raza S, Kaplan L, Grill E, Zimmerman N, Mason C, Abella B, Reilly P. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial. JAMA Surg. 2019 Nov 1;154(11):994-1003. doi: 10.1001/jamasurg.2019.2884.

Reference Type: DERIVED

PMID: 31461138 (View on PubMed)

Other Identifiers

811293

Identifier Type: -

Identifier Source: org_study_id