Rapid Response VA-ECMO in Refractory Out-of-hospital Cardiac Arrest (RESuSCITATe)

ECPR Treatment Protocol: Rapid Response VA-ECMO in Refractory Out-of-hospital Cardiac Arrest (RESuSCITATe Registry)

A selected group of patients with refractory cardiac arrest may benefit from inhospital treatment and this may warrant transfer to the hospital with ongoing CPR. In patients with VF or ventricular tachycardia (VT) the underlying cause may be reversible and damage to other organs is limited at the time of the arrest. Many patients will have a coronary event that can be treated by angioplasty. However, up to now absence of ROSC poses a barrier for angioplasty, and most patients are therefore not even transported to a hospital. With the use of extra corporeal membrane oxygenation (ECMO) the circulation can be restored immediately, providing time to diagnose and treat the underlying cause of the cardiac arrest. International cohort studies show that a strategy of pre-hospital triage and transport to a cardiac arrest expertise center for "rapid-response" ECMO and coronary revascularization is feasible and improves survival.

A clinical pathway will encompass intense cooperation and optimal logistics between several paramedical and medical disciplines, i.e. from prehospital ambulance service to intensive care. Incorporation of mechanical chest compressions devices (LUCAS™), rapid-response veno-arterial (VA-)ECMO (Cardiohelp, Maquet), and ECMO assisted revascularization in a dedicated clinical pathway will offer a potential lifesaving treatment option that is in accordance with the recommendations in the current Guidelines.

The aim of the study is to investigate the feasibility of a new local clinical pathway in our hospital to provide ECPR for refractory OHCA patients.

Study Overview

• Status: Withdrawn
• Conditions: Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Procedure: Extracorporeal Cardiopulmonary Resuscitation

Detailed Description

Coronary heart disease is the leading cause of cardiac arrest. The incidence of cardiac arrest in Europe is between 0.4 and 1 per 1000 inhabitants per year, thus involving between 350.000 and 700.000 people per year. Approximately, 275.000 of these cardiac arrests are treated by the emergency medical service (EMS) in Europe. (1) Survival after cardiac arrest varies from less than 5% to 60% according to the characteristics of the cardiac arrest event (e.g. cardiac etiology, witnessed arrest, initial recorded rhythm (shockable: ventricular fibrillation (VF), ventricular tachycardia (VT) or not shockable).(1) Cardiac arrest patients, who despite conventional cardiopulmonary resuscitation (CPR) do not achieve return of spontaneous circulation (ROSC) within 10-20 minutes of advanced life support (ALS) have the worst prognosis with rates of survival to hospital discharge of 2-11%.

A selected group of patients with refractory cardiac arrest may benefit from very aggressive in-hospital treatment and this may warrant transfer to the hospital with ongoing CPR. In patients with VF or ventricular tachycardia (VT) the underlying cause may be reversible and damage to other organs is limited at the time of the arrest. Many patients will have a coronary event that can be treated by angioplasty. However, up to now absence of ROSC poses a barrier for angioplasty, and most patients are therefore not even transported to a hospital.

With the use of extra corporeal membrane oxygenation (ECMO) the circulation can be restored immediately, providing time to diagnose and treat the underlying cause of the cardiac arrest. International cohort studies show that a strategy of pre-hospital triage and transport to a cardiac arrest expertise center for "rapid-response" ECMO and coronary revascularization is feasible and improves survival. The recent 2015 European Resuscitation Council Guidelines for Resuscitation position extracorporeal CPR (ECPR) as follows: "ECPR should be considered as a rescue therapy for those patients in whom initial advanced life support (ALS) measures are unsuccessful and to facilitate specific interventions (e.g. coronary angiography and percutaneous coronary intervention (PCI) or pulmonary thrombectomy for massive pulmonary embolism)".(2) A recent meta-analysis performed by our group supports ECMO in this setting. (3)

Currently, a strong pre-hospital and clinical pathway for acute myocardial infarction exists in the greater Amsterdam region / Noord-Holland region, i.e. "Lifenet protocol". The Academic Medical Center is an international recognized center with the ARREST program to evaluate treatments for out-of-hospital cardiac arrest (OHCA).(4) However, a dedicated clinical pathway for refractory OHCA patients does not yet exist. Integration of the "Lifenet protocol" and ARREST program would provide an ideal setting to create and install a dedicated clinical pathway for these cardiac arrest patients.

The existing clinical pathway for cardiac arrest patients will be optimized and upgraded to be able to provide ECPR for refractory cardiac arrest patients. This clinical pathway will encompass intense cooperation and optimal logistics between several paramedical and medical disciplines, i.e. from pre-hospital ambulance service to intensive care. Incorporation of mechanical chest compressions devices (LUCAS™), rapid-response veno-arterial (VA-)ECMO (Cardiohelp, Maquet), and ECMO assisted revascularization in a dedicated clinical pathway will offer a potential lifesaving treatment option that is in accordance with the recommendations in the current Guidelines.

The aim of the study is to investigate the feasibility of a new local clinical pathway to provide ECPR for refractory OHCA patients.

• Study Type: Observational

Contacts and Locations

Study Locations

• Netherlands
  • N-Holland
    • Amsterdam, N-Holland, Netherlands, 1105AZ
      • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with refractory OHCA due to VF/VT, witnessed cardiac arrest and basic life support before EMS arrival.

Description

Inclusion Criteria:

• Witnessed arrest
• Bystander CPR initiated before EMS arrival or EMS-witnessed arrest
• VF/VT as first recorded rhythm by EMS or shock delivered by AED
• No ROSC within 10 minutes after EMS arrival
• Ambulance transport with mechanical chest compression device

Exclusion Criteria:

• Confirmation of ROSC
• End-tidal CO2 < 10 mmHg
• Known terminal disease (eg. cancer)

• Known severe comorbidity

  • Severe chronic pulmonary disease (GOLD classification 3 or 4)
  • Heart failure NYHA classification 3 or 4
  • Known history of bifemoral surgery
• Do Not Resuscitate (DNR) order
• Expected time from transport decision to start ECMO >60 minute

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year mortality	assessed through study completion: at 1-year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse outcomes	Major adverse cardiac events (MACE) (death, myocardial infarction, revascularization, stent thrombosis, stroke, bleeding); CPR-related complications (chest wall compartment syndrome, pneumothorax, chylothorax, pulmonary hemorrhage); ECMO-related complications (bleeding requiring transfusion or surgery, stroke, sepsis, limb ischemia requiring intervention, system or cannula change); Other complications (acute renal failure, ulcer bleeding, pneumonia, sepsis)	assessed through study completion: for the time in the hospital , at 30-days and at 1-year.
Other clinical endpoints: Mortality rate - patients not treated with ECPR in comparison to patients treated with ECPR	Mortality rate of patients treated with ECPR in comparison to refractory OHCA patients treated outside of the hours in which ECPR can take place	assessed through study completion: at 30-days, at 1-year after inclusion of patient
Percentage of successful cannulations		assessed through study completion: at 1 year and at the end of study inclusion period (expected to be at 1.5 years)
Neurological outcome at 6 months on the cerebral performance category scale (CPC)	measured with CPC scale: CPC 1A return to normal cerebral function and normal living CPC 2 Cerebral disability but sufficient function for independent activities of daily living CPC 3 Severe disability, limited cognition, inability to carry out independent existence CPC 4 Coma CPC 5 Brain death	assessed through study completion: at 6 months after inclusion of patient.
Quality of life at 6 months assessed by Short form 36 (SF-36)	measured with quality of life assesment form Short form 36 (SF-36). The SF-36 comprises 36 items and contains eight subscales: physical functioning, social functioning, physical role functioning, emotional role functioning, mental health, vitality, bodily pain and general health. Scores are expressed on a scale of 0-100, higher values indicate better quality of life and wellbeing.	assessed through study completion: at 6 months after inclusion of patient.
Rate of eligible / ineligible patients treated with ECPR	How many patients that were treated with ECPR were retrospectively eligible for treatment with ECPR, in comparison to how many patients were treated, but not eligible.	assessed through study completion: at 1 year and at the end of study inclusion period (expected to be at 1.5 years)
Noted reasons for non-adherence to the eligibility criteria ECPR	If patients were treated with ECPR, but were not eligible, what were reasons to do so? (for instance: no knowledge beforehand of ineligibility, or, knowledge beforehand of ineligibility but expert decision to treat, etc.)	assessed through study completion: at 1 year and at the end of study inclusion period (expected to be at 1.5 years)
Number of patients with complete data collection		assessed through study completion: at 1 year and at the end of study inclusion period (expected to be at 1.5 years)
Rate of eligible / ineligible patients not treated with ECPR	How many patients that were not treated with ECPR were retrospectively eligible for treatment with ECPR, in comparison to how many patients were not treated, and not eligible.	assessed through study completion: at 1 year and at the end of study inclusion period (expected to be at 1.5 years)
30-days mortality		assessed through study completion: at 30-days

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Jose P.S. Henriques, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2018
• Primary Completion (Anticipated): December 2, 2019
• Study Completion (Anticipated): July 2, 2020

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: September 3, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: mechanical circulatory support; extra corporeal membrane oxygenation; Extra corporeal Life support; extracorporeal cardiopulmonary resuscitation; refractory out-of-hospital cardiac arrest; mechanical chest compressions
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: ECPR-062018-UAMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No