Vasopressin in Traumatic Hemorrhagic Shock Study

Shock Clinical Trial

Official title:

A Multicenter, Randomized, Controlled Trial Assessing Arginine Vasopressin Versus Saline Placebo in Refractory Traumatic Hemorrhagic Shock Patients (VITRIS-study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00379522
• Other study ID #: Vitris
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 21, 2006
• Last updated: November 4, 2014
• Start date: July 2010
• Est. completion date: October 2014

Study information

• Verified date: November 2014
• Source: Medical University Innsbruck
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemorrhagic Shock
• Hypovolemia
• Shock
• Shock, Hemorrhagic

Intervention

Drug:
• Vasopressin
10 minutes after standard shock treatment 10 IU arginine vasopressin will be injected; if shock persists for 5 minutes, another 10 IU arginine vasopressin will be injected; after 5 minutes persisting shock, the last 10 IU arginine vasopressin will be injected; Total duration: approx. 15 minutes; Dose per intravenous injection: 10 IU; max. dose: 30 IU arginine vasopressin
• Saline placebo
Placebo for arginine vasopressin

Locations

Country	Name	City	State
Austria	HEMS Ybbsitz / Hospital Amstetten	Amstetten	Lower Austria
Austria	Medical University of Graz	Graz	Styria
Austria	Medical University of Innsbruck	Innsbruck	Tyrol
Austria	Hospital Krems	Krems	Lower Austria
Austria	Hospital Linz	Linz	Upper Austria
Austria	Hospital Salzburg	Salzburg
Austria	HEMS Suben / Landeskrankenhaus Schärding	Schaerding	Upper Austria
Austria	Hospital Wiener Neustadt	Wiener Neustadt	Lower Austria
Germany	University Hospital of Dresden	Dresden
Germany	University Hospital of Goettingen	Goettingen
Germany	University Hospital of Mannheim	Mannheim
Germany	BG-Unfallklinik Murnau	Murnau
Germany	Ev. Jung-Stilling-Krankenhaus	Siegen
Germany	Bundeswehrkrankenhaus Ulm	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Volker Wenzel

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (7)

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. — View Citation

Raedler C, Voelckel WG, Wenzel V, Krismer AC, Schmittinger CA, Herff H, Mayr VD, Stadlbauer KH, Lindner KH, Königsrainer 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):1759-66, table of contents. — View Citation

Schummer W, Schummer C, Fuchs J. [Vasopressin]. Anaesthesist. 2005 Jul;54(7):707-8. German. — View Citation

Stadlbauer KH, Wagner-Berger HG, Raedler C, Voelckel WG, Wenzel V, Krismer AC, Klima G, Rheinberger K, Nussbaumer W, Pressmar D, Lindner KH, Königsrainer 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. — View 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):830-2. — View 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. — View Citation

Voelckel WG, Raedler C, Wenzel V, Lindner KH, Krismer AC, Schmittinger CA, Herff H, Rheinberger K, Königsrainer 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary end point will be hospital admission rate		time from trauma to hospital admission	No
Secondary	Hemodynamic variables		time from trauma to hospital discharge	No
Secondary	Fluid resuscitation requirements		time from trauma to hospital discharge	No
Secondary	Hospital discharge rate		time from trauma to hospital discharge	No

External Links

•   Study Homepage