Clinical trial NCT00379522: Vasopressin in Traumatic Hemorrhagic Shock Study
Official title: A Multicenter, Randomized, Controlled Trial Assessing Arginine Vasopressin Versus Saline Placebo in Refractory Traumatic Hemorrhagic Shock Patients (VITRIS-study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Shock
Hypovolemia
Hemorrhagic Shock
Keywords: hemorrhagic
shock
traumatic
shock treatment
vasopressin
Circulatory Collapse
Hypovolemic Shock
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2006-09-22
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the present trial is therefore to assess effects of arginine vasopressin vs. saline placebo on hospital admission rate (primary end point), as well as hemodynamic variables, fluid resuscitation requirements and hospital discharge rate (secondary study end points) in presumed traumatic hemorrhagic shock patients with a systolic arterial blood pressure \<90 mm Hg after 10 min of standard shock treatment. Accordingly, the study reflects an add-on design to standard traumatic shock therapy.

The hypothesis is that both arginine vasopressin and saline placebo have comparable effects on hemodynamic variables, fluid resuscitation requirements, and hospital admission and discharge rate. The alternative hypothesis is that arginine vasopressin has more beneficial effects on hemodynamic variables, fluid resuscitation requirements, and hospital admission and discharge rate than saline placebo.

Detailed description: The study will be designed as a multicenter, randomized, placebo-controlled clinical trial with blinded assessment of the outcome in a study network with helicopter emergency medical service units in Austria, Germany, Switzerland, Italy, Czech Republic and the Netherlands.

The protocol, information and consent procedure will be approved by the institutional review board of each participating center. Since this is a study randomizing unconscious patients who are unable to give informed consent at the time of randomization (§43a Emergency study), the requirement of informed consent is planned to be waived in accordance with the ethical standards of national legislation in Germany, Austria, Switzerland, Italy, Czech Republic and the Netherlands and the guidelines for good clinical practice of the European Agency for the Evaluation of Medicinal products. Depending on the patient's outcome, either the surviving patient, or the patient's family in case of death of the patient or in case that the patient survives but remains mentally handicapped will be informed about the trial (see appendix for patient information sheet); the protocol specifies that if there are any objections, the patient will be withdrawn from the study.

Treatment assignments of blinded study drugs will be randomly generated by computer in blocks of two, with stratification according to center. Before the start of the trial, staff at participating centers will be informed about the rationale of the protocol and the study; participating centers will be subsequently contacted and visited to ensure proper enrollment.

Eligibility criteria: Inclusion Criteria:

* Adult trauma patients presenting with presumed traumatic hemorrhagic shock (systolic arterial blood pressure \<90 mm Hg) that does not respond to the first 10 min of standard shock treatment \[endotracheal intubation, crystalloid-, colloid-, and hypertonic saline (up to 4 ml/kg) fluid resuscitation, and catecholamine (ephedrine, phenylephrine, norepinephrine, epinephrine) vasopressors\].

Exclusion Criteria:

* Terminal illness
* No intravenous access
* Age \< 18 years
* Injury \> 60 min before randomization
* Known pregnancy
* Cardiac arrest before randomization
* Presence of a do-not-resuscitate order
* Untreated tension pneumothorax
* Untreated cardiac tamponade
* Participation in another clinical study.

Primary outcomes:
measure: Primary end point will be hospital admission rate
timeFrame: time from trauma to hospital admission
Secondary outcomes:
measure: Hemodynamic variables
timeFrame: time from trauma to hospital discharge
measure: Fluid resuscitation requirements
timeFrame: time from trauma to hospital discharge
measure: Hospital discharge rate
timeFrame: time from trauma to hospital discharge
Other outcomes:
Locations:
city: Amstetten
country: Austria
facility: HEMS Ybbsitz / Hospital Amstetten
state: Lower Austria
city: Krems
country: Austria
facility: Hospital Krems
state: Lower Austria
city: Wiener Neustadt
country: Austria
facility: Hospital Wiener Neustadt
state: Lower Austria
city: Graz
country: Austria
facility: Medical University of Graz
state: Styria
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
state: Tyrol
city: Linz
country: Austria
facility: Hospital Linz
state: Upper Austria
city: Schaerding
country: Austria
facility: HEMS Suben / Landeskrankenhaus Schärding
state: Upper Austria
city: Salzburg
country: Austria
facility: Hospital Salzburg
city: Dresden
country: Germany
facility: University Hospital of Dresden
city: Goettingen
country: Germany
facility: University Hospital of Goettingen
city: Mannheim
country: Germany
facility: University Hospital of Mannheim
city: Murnau
country: Germany
facility: BG-Unfallklinik Murnau
city: Siegen
country: Germany
facility: Ev. Jung-Stilling-Krankenhaus
city: Ulm
country: Germany
facility: Bundeswehrkrankenhaus Ulm
Study officials:
affiliation: Innsbruck Medical University, Dep. for Anaesthesia and Crit. Care Management
name: Prof. Dr. Volker Wenzel, M.Sc., M.D.
role: STUDY_CHAIR
References:
citation: Krismer AC, Wenzel V, Voelckel WG, Innerhofer P, Stadlbauer KH, Haas T, Pavlic M, Sparr HJ, Lindner KH, Koenigsrainer A. Employing vasopressin as an adjunct vasopressor in uncontrolled traumatic hemorrhagic shock. Three cases and a brief analysis of the literature. Anaesthesist. 2005 Mar;54(3):220-4. doi: 10.1007/s00101-004-0793-y.
citation: Schummer W, Schummer C, Fuchs J. [Vasopressin]. Anaesthesist. 2005 Jul;54(7):707-8. doi: 10.1007/s00101-005-0854-x. No abstract available. German.
citation: Tsuneyoshi I, Onomoto M, Yonetani A, Kanmura Y. Low-dose vasopressin infusion in patients with severe vasodilatory hypotension after prolonged hemorrhage during general anesthesia. J Anesth. 2005;19(2):170-3. doi: 10.1007/s00540-004-0299-4.
citation: Raedler C, Voelckel WG, Wenzel V, Krismer AC, Schmittinger CA, Herff H, Mayr VD, Stadlbauer KH, Lindner KH, Konigsrainer A. Treatment of uncontrolled hemorrhagic shock after liver trauma: fatal effects of fluid resuscitation versus improved outcome after vasopressin. Anesth Analg. 2004 Jun;98(6):1759-1766. doi: 10.1213/01.ANE.0000117150.29361.5A.
citation: Stadlbauer KH, Wenzel V, Krismer AC, Voelckel WG, Lindner KH. Vasopressin during uncontrolled hemorrhagic shock: less bleeding below the diaphragm, more perfusion above. Anesth Analg. 2005 Sep;101(3):830-832. doi: 10.1213/01.ANE.0000175217.55775.1C. No abstract available.
citation: Stadlbauer KH, Wagner-Berger HG, Raedler C, Voelckel WG, Wenzel V, Krismer AC, Klima G, Rheinberger K, Nussbaumer W, Pressmar D, Lindner KH, Konigsrainer A. Vasopressin, but not fluid resuscitation, enhances survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. Anesthesiology. 2003 Mar;98(3):699-704. doi: 10.1097/00000542-200303000-00018.
citation: Voelckel WG, Raedler C, Wenzel V, Lindner KH, Krismer AC, Schmittinger CA, Herff H, Rheinberger K, Konigsrainer A. Arginine vasopressin, but not epinephrine, improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs. Crit Care Med. 2003 Apr;31(4):1160-5. doi: 10.1097/01.CCM.0000060014.75282.69.
citation: O'Callaghan DJ, Gordon AC. What's new in vasopressin? Intensive Care Med. 2015 Dec;41(12):2177-9. doi: 10.1007/s00134-015-3849-3. Epub 2015 May 7. No abstract available.