Traumatic ShockPhase 2AVERTShockNCT01611935
AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock
A Phase 2 study testing Vasopressin in people with Traumatic Shock, run by University of Pennsylvania at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Shock
- What is being tested?
- Vasopressin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2013to 6 Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital at the Unversity of Pennyslvania
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the 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
- Being tested
- Vasopressin
- Keywords
- trauma, shock, vasopressin, blood transfusion
- Medical subject headings
- Shock, Traumatic, Wounds and Injuries, Shock, Diabetes Insipidus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VasopressinDrug
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 group | Role | What they receive |
|---|---|---|
| Vasopressin | Active comparator | 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 Receives: Drug: Vasopressin |
| Normal Saline | Placebo comparator | 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. Receives: Drug: Vasopressin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Blood Products Transfused
Cumulative number of units of blood products, including packed red blood cells, plasma and platelets measured in liters
Measured: 48 hours following the initiation of therapy
Secondary outcomes (2)
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
Measured: 48 hours following the initiation of therapy
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.
Measured: 30 days post injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study start1 May 2013
- Primary completion6 Sep 2016
- Study completion6 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic ShockStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Trauma Research Institute, United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Carrie A Sims, MD, MS, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611935
- Sponsor's protocol ID
- 811293
- Acronym
- AVERTShock
- Status last verified
- Apr 2019
- First submitted
- 1 Jun 2012
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 31461138
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AVERT Shock: Arginine Vasopressin During the Early Resuscitation of Traumatic Shock
- ClinicalTrials.gov ID
- NCT01611935
- Acronym / sponsor ID
- AVERTShock / 811293
- Conditions
- Traumatic Shock
- Keywords
- trauma, shock, vasopressin, blood transfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Trauma Research Institute, United States Department of Defense
- Study start
- 1 May 2013 (actual)
- Primary completion
- 6 Sep 2016 (actual)
- Study completion
- 6 Sep 2016 (actual)
- First posted
- 5 Jun 2012 (estimated)
- Results
- Posted 21 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vasopressin | Active comparator | Drug: VasopressinVasopressin 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 |
| Normal Saline | Placebo comparator | Drug: VasopressinAn 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VasopressinAfter 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. | Drug | Normal Saline, Vasopressin |
Primary outcome
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
2 secondary outcomes
Need for Vasopressor Requirement Vasopressor Requirement
Time frame: 48 hours following the initiation of therapy
Total Number of Complications
Time frame: 30 days post injury
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31461138Sims 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carrie A Sims, MD, MS principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vasopressin in people with Traumatic Shock, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Blood Products Transfused (time frame: 48 hours following the initiation of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01611935, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019.