Expedited transfer from the scene for refractory out-of-hospital cardiac arrest in Australia: a prospective, multicentre, parallel, open label, randomised clinical trial

BACKGROUND The benefit of expedited intra-arrest transport with ongoing resuscitation versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest (OHCA) is uncertain. We aimed to determine whether expedited intra-arrest transfer to hospital in adults with refractory OHCA improves favourable neurological outcomes. METHODS We conducted a prospective, parallel, multi-centre, open-label randomised, superiority trial across greater Sydney, NSW, Australia. Patients aged 18-70 years with a witnessed OHCA of presumed medical cause, bystander cardiopulmonary resuscitation (CPR), and an initial shockable rhythm or pulseless electrical activity without return of spontaneous circulation after 15 mins of advanced life support or three rounds of professional resuscitation were randomly assigned (1:1) at the scene by New South Wales Ambulance paramedics using a secure online randomisation system. Masking of allocation from ambulance staff and hospital staff receiving the patients was not possible. The intervention consisted of a predefined expedited bundle of pre-hospital care followed by intra-arrest transport with mechanical compression to a cardiac catheterisation centre (15 receiving hospitals) for immediate assessment for coronary angiography, extracorporeal cardiopulmonary resuscitation (ECPR), or both. The control arm consisted of a standard transport strategy of more extended on-scene advanced life support before considering transport and the same therapies. The primary outcome was survival with a good neurological outcome (defined as Cerebral Performance Category [CPC] score of 1-2) at hospital discharge, stratified by initial rhythm. Patients were followed-up until death or for 6 months (last patient followed-up Aug 29, 2024). All analyses were done on an intention-to-treat basis. The trial was prospectively registered with the Australian Clinical Trials Registry, ACTRN12621000668808 and is now complete. Data on safety and adverse events were collected throughout the study period and reported to a data safety monitoring board on a 6 monthly basis. FINDINGS Between July 15, 2021 and March 3, 2024, we enrolled 206 patients. Eight patients were later deemed to be ineligible and one patient was excluded due to a randomisation application failure. 197 patients were therefore enrolled; 102 to the expedited strategy (intervention) and 95 to the standard strategy (control). The median age was 57·0 years (range 47-64); 161 (82%) were men and 78 (40%) were White. At hospital discharge, 15 (15%) of 102 patients in the expedited transportation group were alive with a favourable neurological outcome, compared with 15 (16%) of 95 patients in the standard care group (risk difference -1·1% [95% CI -12·2% to 10·0%]; adjusted relative risk 0·95 [95% CI 0·50 to 1·8], p=0·87). 38 patients had a serious adverse event (19%)-35 (92%) were diagnosed with a hypoxic brain injury (17 [49%] in the expedited arm, 18 [51%] in the standard arm), one (3%) had a cerebral stroke, one (3%) had a pulmonary haemorrhage, and one (3%) had a gastrointestinal haemorrhage (all in the standard arm). Adverse events were evenly distributed between treatment arms. No unanticipated (ie, expected sequelae seen in a cardiac arrest trial or in intensive care) adverse events were identified. INTERPRETATION Among patients with refractory out-of-hospital cardiac arrest, expedited intra-arrest transport did not significantly improve survival with neurologically favourable outcome. However, the study might have been underpowered to detect a smaller than expected treatment effect.