Early Initiation of Extracorporeal Life Support in Refractory OHCA

Not Applicable

Completed

• Conditions: Cardiac Arrest; Out-Of-Hospital Cardiac Arrest; Sudden Cardiac Death
• Interventions: Procedure: Extracorporeal cardiopulmonary resuscitation (ECPR)

• Registration Number: NCT03101787
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-03-30
• Study First Submitted QC: 2017-03-30
• Study First Posted: 2017-04-05
• Study Start: 2017-05-01
• Primary Completion: 2021-02-10
• Study Completion: 2022-02-10
• Status Verified: 2022-08
• Last Update Submitted: 2022-10-14
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

1. ≥18 - ≤70 years
2. Witnessed OHCA (by bystanders)
3. Initial rhythm of VF/VT or AED administered
4. Bystander BLS

Exclusion Criteria

1. ROSC within 15 minutes of conventional CPR with sustained hemodynamic recovery
2. Terminal heart failure (NYHA III or IV)
3. Severe pulmonary disease (COPD GIII of GIV)
4. Disseminated oncological disease
5. Obvious or suspected pregnancy
6. Bilateral femoral bypass surgery
7. Known contraindications for ECPR
8. Known pre-arrest CPC-score of 3 or 4
9. Known limitations in therapy or a Do Not Resuscitate-order
10. Multitrauma (Injury Severity Score >15)
11. Expected time-to-start cannulation > 60 minutes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ECPR protocol	Extracorporeal cardiopulmonary resuscitation (ECPR)	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.

Primary Outcome Measures

Name	Time	Method
30-day survival rate with favorable neurological status	30 days	Favorable neurological status is defined as 1 or 2 on the using Cerebral Performance Category scale

Secondary Outcome Measures

Name	Time	Method
Costs per gained QALY for ECPR vs. CCPR	1 year	What are the costs per gained QALY for ECPR vs. CCPR
Length of stay at the ICU	1 year	Is there a difference in length of stay at the ICU between the treatment groups
Neurological outcome on the CPC scale	30 days, 3 months, 6 months and 12 months	Does ECPR improve the neurological outcome at 30 days, 3 months, 6 months and 12 months on the CPC scale
Quality Adjusted Life Years (QALY's)	30 days, 3 months, 6 months and 12 months	Does ECPR improve the amount of Quality Adjusted Life Years (QALY's) at 30 days, 3 months, 6 months and 12 months
Reason for discontinuation of treatment between the treatment groups	Within 1 year	Is there a difference in reason for discontinuation of treatment between the treatment groups
Time to return of circulation	Within 1 year	What is the time to return of circulation
Additional costs of ECPR with respect to CCPR	1 year	What are the additional costs of ECPR with respect to CCPR
Length of stay at the hospital	1 year	Is there a difference in length of stay at the hospital between the treatment groups
Duration of clinical rehabilitation time	1 year	Is there a difference in the duration of clinical rehabilitation time
Duration of mechanical ventilation	1 year	Is there a difference in the duration of mechanical ventilation between treatment groups
Need for renal replacement therapy	1 year	Is there a difference in need for renal replacement therapy between the treatment groups
Acute kidney injury according to the RIFLE criteria	1 year	Is there a difference in acute kidney injury according to the RIFLE criteria
Time to target hypothermia	1 year	Is there a difference in time to target hypothermia between the treatment groups
Difference in metabolic markers between treatment groups	6 days	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
Difference in metabolic markers between between the survivors and non-survivors	6 days	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

Trial Locations

Locations (10)

Isala Klinieken; 🇳🇱 Zwolle, Overijssel, Netherlands

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Maastricht UMC; 🇳🇱 Maastricht, Limburg, Netherlands

St. Antonius Hospital; 🇳🇱 Nieuwegein, Utrecht, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Noord-Brabant, Netherlands

Academisch Medisch Centrum; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Zuid-Holland, Netherlands

Onze Lieve Vrouwen Gasthuis; 🇳🇱 Amsterdam, Netherlands

HagaZiekenhuis; 🇳🇱 Den Haag, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands