Early Initiation of Extracorporeal Life Support in Refractory OHCA

Study Overview
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Brief Summary
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Despite adequate conventional cardiopulmonary resuscitation (CCPR) and attempted defibrillation, a considerable number of patients in cardiac arrest fail to achieve sustained return of spontaneous circulation. The INCEPTION trial is a multicenter, randomized controlled trial that will explore extracorporeal cardiopulmonary resuscitation (ECPR) in patients in refractory out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation or tachycardia. It aims to determine the effect on survival and neurological outcome. Additionally, it will evaluate the feasibility and cost-effectiveness of ECPR.

Detailed Description
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There are approximately 275,000 cases of out-of-hospital cardiac arrest (OHCA) per year in Europe, of which two-thirds have a primary cardiac origin. However, despite adequate conventional cardiopulmonary resuscitation (CCPR) and attempted defibrillation, a considerable number of these patients fail to achieve sustained return of spontaneous circulation (ROSC). Treatment of the underlying cause of the arrest, in most cases coronary artery occlusion, is paramount. But in the absence of ROSC, the possibilities to perform these life-saving interventions are limited. Continued CCPR is currently the standard of care for these patients. Initiation of extracorporeal cardiopulmonary resuscitation (ECPR) restores circulation, with the potential to minimize (or even reversing) organ damage, prevent re-arrest due to ischemia-triggered myocardial dysfunction and providing a bridge to possible diagnosis and treatment. Several studies have demonstrated that ECPR is feasible and may be advantageous with respect to survival and neurological outcome. The INCEPTION trial aims to compare ECPR to CCPR in the population that is expected to benefit the most from this intervention: young patients presenting with ventricular fibrillation or tachycardia (VF/VT) and a refractory cardiac arrest. Furthermore, it will provide data on the cost-effectiveness of this intervention, which to date has been unavailable. Although the costs may prove to be high, the gain in quality-adjusted life years (QALY's) may be substantial given the fact that most patients are relatively young and the current alternative carries a poor prognosis. This can determine whether ECPR should be pursued as a standard of care in patients with refractory arrest.

Official Title
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Early Initiation of Extracorporeal Life Support in Refractory OHCA (INCEPTION)

Conditions
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Cardiac Arrest, Out-Of-Hospital Cardiac Arrest, Sudden Cardiac Death

Intervention / Treatment
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* Procedure: Extracorporeal cardiopulmonary resuscitation (ECPR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 - ≤70 years Witnessed OHCA (by bystanders) Initial rhythm of VF/VT or AED administered Bystander BLS Exclusion Criteria: ROSC within 15 minutes of conventional CPR with sustained hemodynamic recovery Terminal heart failure (NYHA III or IV) Severe pulmonary disease (COPD GIII of GIV) Disseminated oncological disease Obvious or suspected pregnancy Bilateral femoral bypass surgery Known contraindications for ECPR Known pre-arrest CPC-score of 3 or 4 Known limitations in therapy or a Do Not Resuscitate-order Multitrauma (Injury Severity Score >15) Expected time-to-start cannulation > 60 minutes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: CCPR protocol<br>Preclinical Cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) and rapid transport to the emergency department with ongoing mechanical CPR and advanced cardiac life support (ACLS). Clinical Upon the patient's arrival, the standard of care (CCPR) will be continued according to ERC guidelines. No special preparations for the trial are needed before the patient's arrival. | |
| Experimental: ECPR protocol<br>Preclinical Cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) and transport to the emergency department with ongoing mechanical CPR and advanced cardiac life support (ACLS). Clinical The ECPR team is mobilized while the patient is transported to the hospital. Initiation of extracorporeal cardiopulmonary resuscitation (ECPR). Time from arrest to start of cannulation is < 60 minutes. | Procedure: Extracorporeal cardiopulmonary resuscitation (ECPR)<br>* In addition to the routine response team, the ECLS team are called to the ED while the patient is transported to the hospital. The team consists of a physician skilled and qualified in femoral cannulation, a perfusionist and a scrub nurse. Upon the patient's arrival at the emergency department, CPR will be continued, with continuation of mechanical chest compressions with minimization of interruptions. Time from arrest to start of cannulation is < 60 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day survival rate with favorable neurological status | Favorable neurological status is defined as 1 or 2 on the using Cerebral Performance Category scale | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological outcome on the CPC scale | Does ECPR improve the neurological outcome at 30 days, 3 months, 6 months and 12 months on the CPC scale | 30 days, 3 months, 6 months and 12 months | 
| Quality Adjusted Life Years (QALY's) | Does ECPR improve the amount of Quality Adjusted Life Years (QALY's) at 30 days, 3 months, 6 months and 12 months | 30 days, 3 months, 6 months and 12 months | 
| Reason for discontinuation of treatment between the treatment groups | Is there a difference in reason for discontinuation of treatment between the treatment groups | Within 1 year | 
| Time to return of circulation | What is the time to return of circulation | Within 1 year | 
| Additional costs of ECPR with respect to CCPR | What are the additional costs of ECPR with respect to CCPR | 1 year | 
| Costs per gained QALY for ECPR vs. CCPR | What are the costs per gained QALY for ECPR vs. CCPR | 1 year | 
| Length of stay at the ICU | Is there a difference in length of stay at the ICU between the treatment groups | 1 year | 
| Length of stay at the hospital | Is there a difference in length of stay at the hospital between the treatment groups | 1 year | 
| Duration of clinical rehabilitation time | Is there a difference in the duration of clinical rehabilitation time | 1 year | 
| Duration of mechanical ventilation | Is there a difference in the duration of mechanical ventilation between treatment groups | 1 year | 
| Need for renal replacement therapy | Is there a difference in need for renal replacement therapy between the treatment groups | 1 year | 
| Acute kidney injury according to the RIFLE criteria | Is there a difference in acute kidney injury according to the RIFLE criteria | 1 year | 
| Time to target hypothermia | Is there a difference in time to target hypothermia between the treatment groups | 1 year | 
| Difference in metabolic markers between treatment groups | Is there a difference in metabolic markers such as (1) pH, (2) etCO2, (3) ScVO2 and (4) lactate at arrival at the ED, right after initialization of circulation (either by ROSC or ECPR), 1, 2, 3, 4, 5 and 6 hours after return of circulation and at 1, 2, 3, 4, 5 and 6 days after the OHCA between the treatment groups | 6 days | 
| Difference in metabolic markers between between the survivors and non-survivors | Is there a difference in metabolic markers such as (1) pH, (2) etCO2, (3) ScVO2 and (4) lactate at arrival at the ED, right after initialization of circulation (either by ROSC or ECPR), 1, 2, 3, 4, 5 and 6 hours after return of circulation and at 1, 2, 3, 4, 5 and 6 days after the OHCA between the survivors and non-survivors | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECPR, Extracorporeal CardioPulmonary Resuscitation, OHCA, Out-of-Hospital Cardiac Arrest, CPR, CardioPulmonary Resuscitation, ECMO, ExtraCorporeal Membrane Oxygenation, Refractory Cardiac Arrest