Xenon for Neuroprotection During Post-Cardiac Arrest Syndrome in Comatose Survivors of an Out of Hospital Cardiac Arrest

Study Overview
=================
Brief Summary
-----------------
XePOHCAS: Prospective, randomized, multicenter interventional trial in adult subjects with out-of-hospital cardiac arrest comparing treatment with standard-of-care post-cardiac arrest intensive care (which is targeted temperature management [TTM]) to xenon by inhalation plus standard-of-care post-cardiac arrest intensive care (including TTM).

Detailed Description
-----------------
XePOHCAS: Primary Objective: To evaluate whether there is a difference in functional outcome with xenon 50% and oxygen during targeted temperature management (TTM) compared with similar oxygen content in air during TTM in comatose subjects with sustained restoration of spontaneous circulation (ROSC) within 30 minutes after out-of-hospital cardiac arrest (OHCA). Secondary Objective: To evaluate whether there is a difference in survival with xenon 50% and oxygen during targeted temperature management (TTM) compared with similar oxygen content in air during TTM in comatose subjects with sustained restoration of spontaneous circulation (ROSC) within 30 minutes after out-of-hospital cardiac arrest (OHCA).

Official Title
-----------------
XePOHCAS - Xenon by Inhalation for Post Out of Hospital Cardiac Arrest Syndrome

Conditions
-----------------
Post-Cardiac Arrest Syndrome

Intervention / Treatment
-----------------
* Combination Product: Xenon


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age at least 18 years but less than or equal to 80 years Presumed cardiac cause of arrest Sustained (>20 minutes) spontaneous circulation upon arrival in the emergency department No response to verbal commands on arrival to emergency department and prior to randomization (Glasgow Coma Scale score of <8) Attending decision that patient is eligible for TTM Exclusion Criteria: Written do not attempt resuscitation reported to providers before randomization Traumatic etiology of arrest, defined as concomitant blunt, penetrating, or burn-related injury, or uncontrolled bleeding or exsanguination Suspected or known stroke or intracranial hemorrhage Unwitnessed cardiac arrest No-flow (cardiac arrest to initiation of cardiopulmonary resuscitation/defibrillation) time of >10 minutes Sustained restoration of spontaneous circulation (ROSC) greater than 30- minutes post-arrest Interval from arrival at the emergency department to randomization for intervention of >4 hours. Hypothermia (<30°C core temperature) Bed-bound prior to cardiac arrest Unconsciousness before cardiac arrest (cerebral trauma, spontaneous cerebral hemorrhage, intoxication etc.) Coagulopathy Systolic arterial pressure <80 mmHg or mean arterial pressure <60 mmHg lasting more than 30 minutes after ROSC Known pregnancy Have received an investigational drug, device, or biologic product within 30-days Known terminal phase of chronic illness Hypoxemia (SaO2 <85%) for >15 minutes after ROSC Inability to maintain SaO2 >90% on an FiO2 of 50% Having any other clinically significant laboratory abnormality, medical condition (such as intrinsic liver disease or severe chronic obstructive pulmonary disease), or social circumstance that, in the investigator's opinion, makes it inappropriate for the patient to participate in this clinical trial Logistically impossible to provide intervention Have any condition that would impact the evaluation of modified Rankin Scale (mRS)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: TH/TTM<br>Protocol-directed standard of care (including TH/TTM) dictated by the 2015 guidelines for Post-Cardiac Arrest Care from the American Heart Association and the European Resuscitation Council. Mechanical Ventilation delivered by individual site-sanctioned ventilator. | |
| Active Comparator: TH/TTM plus Xenon<br>50% xenon gas in addition to standard of care, including therapeutic hypothermia/targeted temperature management (TH/TTM). | Combination Product: Xenon<br>* 50% xenon by inhalation, delivered by customized xenon delivery system, that includes a ventilator, for the 24h period of TH/TTM. The inhalation therapy is provided in combination with protocol-directed Post-Cardiac Arrest Care dictated by the 2015 guidelines from the American Heart Association and the European Resuscitation Council.<br>* Other names: XENEX;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional outcome: degree of functional independence measured using a modified Rankin Scale (mRS) | The degree of functional independence will be measured using a modified Rankin Scale (mRS) | 30 days after the cardiac arrest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival: number of survivors | The number of survivors will be measured | 30 days after the cardiac arrest | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ischemic-reperfusion injury, out of hospital cardiac arrest