Clinical trial NCT03101787: Early Initiation of Extracorporeal Life Support in Refractory OHCA
Official title: Early Initiation of Extracorporeal Life Support in Refractory OHCA (INCEPTION)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiac Arrest
Out-Of-Hospital Cardiac Arrest
Sudden Cardiac Death
Keywords: ECPR
Extracorporeal CardioPulmonary Resuscitation
OHCA
Out-of-Hospital Cardiac Arrest
CPR
CardioPulmonary Resuscitation
ECMO
ExtraCorporeal Membrane Oxygenation
Refractory Cardiac Arrest
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Getinge Group
First posted: 2017-04-05
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 30-day survival rate with favorable neurological status
timeFrame: 30 days
Secondary outcomes:
measure: Neurological outcome on the CPC scale
timeFrame: 30 days, 3 months, 6 months and 12 months
measure: Quality Adjusted Life Years (QALY's)
timeFrame: 30 days, 3 months, 6 months and 12 months
measure: Reason for discontinuation of treatment between the treatment groups
timeFrame: Within 1 year
measure: Time to return of circulation
timeFrame: Within 1 year
measure: Additional costs of ECPR with respect to CCPR
timeFrame: 1 year
measure: Costs per gained QALY for ECPR vs. CCPR
timeFrame: 1 year
measure: Length of stay at the ICU
timeFrame: 1 year
measure: Length of stay at the hospital
timeFrame: 1 year
measure: Duration of clinical rehabilitation time
timeFrame: 1 year
measure: Duration of mechanical ventilation
timeFrame: 1 year
measure: Need for renal replacement therapy
timeFrame: 1 year
measure: Acute kidney injury according to the RIFLE criteria
timeFrame: 1 year
measure: Time to target hypothermia
timeFrame: 1 year
measure: Difference in metabolic markers between treatment groups
timeFrame: 6 days
measure: Difference in metabolic markers between between the survivors and non-survivors
timeFrame: 6 days
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
state: Limburg
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
state: Noord-Holland
city: Zwolle
country: Netherlands
facility: Isala Klinieken
state: Overijssel
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwen Gasthuis
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
Study officials:
affiliation: Maastricht UMC
name: Marcel van de Poll, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bol ME, Suverein MM, Lorusso R, Delnoij TSR, Brandon Bravo Bruinsma GJ, Otterspoor L, Kuijpers M, Lam KY, Vlaar APJ, Elzo Kraemer CV, van der Heijden JJ, Scholten E, Driessen AHG, Montero Cabezas JM, Rittersma SZH, Heijnen BG, Taccone FS, Essers B, Delhaas T, Weerwind PW, Roekaerts PMHJ, Maessen JG, van de Poll MCG. Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial. Am Heart J. 2019 Apr;210:58-68. doi: 10.1016/j.ahj.2018.12.008. Epub 2018 Dec 14.