Background: Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. Methods: For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18–75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. Findings: Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36–73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6–30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3–67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7–59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. Interpretation: Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. Funding: National Heart, Lung, and Blood Institute.
Bibliographical noteFunding Information:
DY reports US National Institutes of Health (NIH) grants to study cardiopulmonary resuscitation (CPR) and cardiac arrest from NHLBI, and a grant from the Helmsley Charitable Trust for community implementation of a mobile ECMO programme in the St Paul Minneapolis metropolitan area. TPA reports NIH grants to study CPR and cardiac arrest from NHLBI. All other authors declare no competing interests.
We would like to thank Sue Lowry for development and management of the ARREST trial database and nurses Gretchen Peichel, Barbara Bruhn-Ding, Deborah Wilder, and Julie Longman in the Lillehei Clinical Research Unit of the Division of Cardiology who contributed to the successful completion of this trial in obtaining consent, data collection, and analysis, as well as FDA related communications. We would also like to thank Brandy Harrington who facilitated all communications with the IRB.
© 2020 Elsevier Ltd
PubMed: MeSH publication types
- Clinical Trial, Phase II
- Comparative Study
- Journal Article
- Randomized Controlled Trial
- Research Support, N.I.H., Extramural