Vasopressin in Traumatic Hemorrhagic Shock Study

Study Overview
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Brief Summary
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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
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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appendix for patient information sheet); the protocol specifies that if there are any objections, the patient will be withdrawn from the study.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.

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

Conditions
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Shock, Hypovolemia, Hemorrhagic Shock

Intervention / Treatment
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* Drug: Vasopressin
* Drug: Saline placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vasopressin<br>Vasopressin, 10 I.U./4 ml, Solution for Injection | Drug: Vasopressin<br>* 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<br>* Other names: Pitressin;|
| Placebo Comparator: Saline<br>Saline placebo 4 ml, Solution for Injection | Drug: Saline placebo<br>* Placebo for arginine vasopressin<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary end point will be hospital admission rate |  | time from trauma to hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic variables |  | time from trauma to hospital discharge | 
| Fluid resuscitation requirements |  | time from trauma to hospital discharge | 
| Hospital discharge rate |  | time from trauma to hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemorrhagic, shock, traumatic, shock treatment, vasopressin, Circulatory Collapse, Hypovolemic Shock