Clinical trial NCT06692075: Emergency Total ECLS vs Standard ACLS With ECMO Bailout for Survival in Refractory OHCA
Official title: Emergency Total Extracorporeal Life Support Versus Standard Advanced Cardiac Life Support With ECMO Bailout for Survival With Favorable Neurological Outcome in Refractory Out-of-Hospital Cardiac Arrest
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Out-of-hospital Cardiac Arrest (OHCA)
Keywords: out-of-hospital cardiac arrest
extracorporeal life support
advanced cardiac life support
sudden death
Lead sponsor: Taipei Medical University Shuang Ho Hospital
Sponsor class: OTHER
First posted: 2024-11-18
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two arms are designed. One is the total ECLS arm to start emergency ECMO supported cardiopulmonary resuscitation immediately after the arrival of eligible OHCA patients at the emergency department. The other is the standard ACLS arm to start standard ACLS cardiopulmonary resuscitation for at least 45 minutes from collapse and 119 call or at least 15 minutes after arrival at the emergency department.
Primary purpose: TREATMENT

Brief summary: The goal of the clinical trial is to learn if early extracorporeal life support ( ECLS ) will save more out-of-hospital cardiac arrest ( OHCA ) patients with good neurological outcome. It will also learn if emergency ECLS is safe in the OHCA rescue. Researchers aim to investigate if emergency total ECLS is better than standard advanced cardiac life support ( ACLS ) first, followed by bailout ECMO if required, for survival with favorable neurological outcome in OHCA patients. Participants meeting criteria of OHCA with witness, bystander CPR, shockable initial rhythm with repeated defibrillation, and transport time less than 30 min will be compared between total ECLS versus standard ACLS first with bailout ECMO protocols. All participants will receive emergency interventional coronary revascularization , intensive care unit therapy , cardiac ward care and up to 180 days of clinical follow up after survival .

Detailed description: Out-of-hospital cardiac arrest ( OHCA ) is a highly lethal emergency, unless return of spontaneous circulation ( ROSC ) is timely achieved by efficient and effective resuscitation. Nevertheless, despite advanced cardiopulmonary resuscitation ( CPR ) with mechanical chest compression, assisted ventilation and automatic external defibrillation, the survival of OHCA patients remains below 10%. Extracorporeal membranous oxygenation ( ECMO ) facilitated life support ( ECLS ) could help hemodynamic stability and improve significantly the survival of refractory OHCA to 25-40 %. On the other hand, the precise role and timing of the ECLS during the emergency management of OHCA remains largely unestablished.

In the present study, we hypothesized that emergency total ECLS is superior to standard ACLS with ECMO bailout for survival with favorable neurological outcome in refractory out-of-hospital cardiac arrest. All OHCA patients meeting the including criteria, i.e. age 18-75 years, witnessed cardiac arrest with bystander CPR, initial shockable rhythm as ventricular fibrillation or pulseless ventricular tachycardia ( VF/pVT ), repeated defibrillation shocks and escorted transportation within 30 minutes from 119 call to arriving emergency department ( ED ) in the hospital would be recruited. Eligible patients will be consecutively randomized at ED in 1:1 ratio, stratified by hospitals, into emergency total ECLS group and standard ACLS with ECMO bailout group. Informed consent is waived in the life-threatening emergency condition. For emergency total ECLS group, OHCA patients will receive early implantation and initiation of ECMO circulation within 15 minutes after randomization or up to 45 minutes after 119 call. For standard ACLS with ECMO bailout group, OHCA patients will receive standard ACLS for at least 45 minutes after collapse or 119 call or at least 15 minutes after ED arrival before calling for bailout ECMO if required. Following return of spontaneous systemic circulation (ROSC) or depending on ECMO circulation, both groups would be transferred to brain and chest computer tomography screening, emergency coronary revascularization intervention and subsequent intensive cardiac care with targeted hypothermia management. Survivals will be treated with guideline directed medical therapy for reduced ejection fraction heart failure and/or implantable cardioverter-defibrillator implantation for prevention of recurrent VT/VF in wards. All survivals will be followed up for medical and neurological status at 30 days, 90 days and 180 days after discharge.

Primary endpoint is survival with favorable neurological outcome at 30 days. Secondary endpoints are survival to discharge with favorable neurological outcome, survival with favorable neurological outcome at 180 days, total duration of cardiopulmonary resuscitation ( CPR ), total duration of mechanical ventilation, total duration of intensive care unit stay, total duration of hospitalization. Safety endpoints will be incidence of serious adverse events related to prolonged CPR, prolonged ischemia, and ECMO systemic perfusion and coronary reperfusion.

The number of subjects to be enrolled according to the primary endpoint of 30 days survival with favorable neurological outcome. With a power of 80%, accepting the level of statistical significance at alpha= 0.05 and based on two-sided Chi-Square test, we estimated 166 participants per arm are needed. This is based on the 30% success rate and 15% success rate of 30-day survival with good neurological outcome of emergency total ECLS intervention and standard ACLS with bailout ECMO (if required) intervention, according to previous trials, plus a 10% drop out rate. Based on two-tailed test, p less than 0.05 is considered statistical significance. If interim analysis is deemed necessary, the significance level will be adjusted accordingly using Bonferroni method. Because of no interim analysis and no stopping point in ITT protocol, there is no criteria for premature termination of the trial. The missing data of the primary and secondary efficacy outcomes will be considered as failure for ITT analysis. Last observations carry forward method will be adapted for the missing data of repeated measurements. The data record will be monitored and audited by the Institutional Review Board of the TMU Shuangho hospital as well as the Data and Safety Monitoring Plan committee.

Eligibility criteria: Inclusion Criteria:

1. adults aged 18-75 years old
2. witnessed cardiac arrest with bystander CPR
3. initial shockable rhythm as ventricular fibrillation or pulseless ventricular tachycardia ( VF/pVT )
4. repeated defibrillation shocks ( more than 2 ) by external defibrillator
5. estimated transportation time from 119 call to arrival at emergency service less than 30 minutes.

Exclusion Criteria:

1. age less than 18 years or more than 75 years old
2. non-shockable initial rhythm, i.e. pulseless electrical activity or asystole
3. acute aortic dissection
4. acute massive pulmonary embolism
5. intracerebral hemorrhage
6. major trauma due to blunt, penetrating or burn injury
7. severe peripheral artery occlusion disease
8. known pregnancy
9. suicide, illicit drug overdose or intoxication
10. known pre-arrest modified Rankin score ( mRS ) more than 3 or cerebral performance category scale ( CPC ) more than 2
11. severe concomitant malignancy with expected life expectancy less than 1 year
12. signed and effective do-not-resuscitation ( DNR ) order
13. absolute contraindications to emergency coronary angiography, including known anaphylactic reaction to angiographic contrast media, acute gastrointestinal bleeding or internal bleeding.

Primary outcomes:
measure: The rate of survival with favorable neurological outcome ( modified Rankin score less than 3 or cerebral performance category scale 1 or 2 ) at 30 days after discharge from hospital, in percentage
timeFrame: From randomization to 30 days after survival discharge from hospital
Secondary outcomes:
measure: Total duration of cardioplumonary resuscitation from on-site CPR by EMS till the stable ROSC or initiation of ECMO life support or the decease of the subject at emergency department up to 30 days after randomization, in minutes
timeFrame: From the start of on-site CPR by EMS till the return of stable ROSC or the initiation of ECMO life support or the decease of the subject at the emergency department up to 30 days after randomization, in minutes
measure: The rate of survival with favorable neurological outcome ( modified Rankin score less than 3 or CPC scale 1 or 2 ) from the date of randomization to the date of discharge from hospital up to 180 days after randomization, in percentage
timeFrame: From the date of randomization to the date of discharge from hospital up to 180 days after randomization, in percentage.
measure: The rate of survival with favorable outcomes ( modified Rankin score less than 3 or cerebral performance category scale 1 or 2 ) at 90 days after discharge from hospital, in percentage
timeFrame: From the date of randomization to 90 days after survival discharge from hospital
measure: The rate of survival with favorable outcomes ( modified Rankin score less than 3 or cerebral performance category scale 1 or 2 ) at 180 days, in percentage
timeFrame: From enrollment to the end of treatment at 180 days
measure: total duration of mechanical ventilation from randomization to discharge from hospital or up to 180 days after randomization , in days
timeFrame: From randomization at the emergency department to discharge from hospital or up to 180 days after randomization
measure: total duration of stay in intensive care ward from randomization to discharge from hospital or up to 180 days after randomization , in days
timeFrame: From the date of randomization to the date of discharge from hospital or up to 180 days after randomization
measure: total duration of hospitalization from the date of randomization to the date of discharge or up to 180 days after randomization , in days
timeFrame: From the date of randomization to the date of discharge from hospital or up to 180 days after randomization, survived or deceased.
Other outcomes:
Locations:
city: New Taipei
country: Taiwan
facility: Shuang Ho Hospital
Study officials:
References: