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

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ClinicalTrials.gov Identifier: NCT01611935
Recruitment Status : Completed
First Posted : June 5, 2012
Results First Posted : May 21, 2019
Last Update Posted : May 21, 2019
Sponsor:
Collaborators:
National Trauma Research Institute
United States Department of Defense
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE June 1, 2012
First Posted Date  ICMJE June 5, 2012
Results First Submitted Date  ICMJE January 28, 2019
Results First Posted Date  ICMJE May 21, 2019
Last Update Posted Date May 21, 2019
Actual Study Start Date  ICMJE May 1, 2013
Actual Primary Completion Date September 6, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: June 4, 2012)
Number of Blood Products Transfused [ Time Frame: 48 hours following the inititation of therapy ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2012)
  • Need for Vasopressor Requirement [ Time Frame: 48 hours following the initiation of therapy ]
  • Development 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 mutiple organ failure, volume of crystalloid requirement within 48 hours post injury, and mortality.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock
Official Title  ICMJE AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Traumatic Shock
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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
    Intervention: Drug: Vasopressin
  • 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.
    Intervention: Drug: Vasopressin
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 30, 2019)
101
Original Estimated Enrollment  ICMJE
 (submitted: June 4, 2012)
100
Actual Study Completion Date  ICMJE September 6, 2016
Actual Primary Completion Date September 6, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01611935
Other Study ID Numbers  ICMJE 811293
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE
  • National Trauma Research Institute
  • United States Department of Defense
Investigators  ICMJE
Principal Investigator: Carrie A Sims, MD, MS University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP