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

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Arrest; Sudden Cardiac Death; Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Procedure: Extracorporeal cardiopulmonary resuscitation (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 Type: Interventional
• Enrollment (Actual): 134
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwen Gasthuis
  • Den Haag, Netherlands
    • HagaZiekenhuis
  • Rotterdam, Netherlands
    • Erasmus MC
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Maastricht UMC
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands
      • Catharina Ziekenhuis
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
      • Academisch Medisch Centrum
  • Overijssel
    • Zwolle, Overijssel, Netherlands
      • Isala Klinieken
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435 CM
      • St. Antonius Hospital
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands
      • Leids Universitair Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CCPR protocol; 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; 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; Getinge Group
• Investigators: Principal Investigator: Marcel van de Poll, MD, PhD, Maastricht UMC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): February 10, 2021
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: March 30, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: ECMO; CPR; Out-of-Hospital Cardiac Arrest; OHCA; ECPR; Extracorporeal CardioPulmonary Resuscitation; CardioPulmonary Resuscitation; ExtraCorporeal Membrane Oxygenation; Refractory Cardiac Arrest
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Death; Heart Arrest; Out-of-Hospital Cardiac Arrest; Death, Sudden, Cardiac
• Other Study ID Numbers: NL58067.068.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No