REfractory VF InterVention with Esmolol- Australia - ‘REVIVE-AUS’

Brief name: Esmolol-based intervention bundle with de-emphasised adrenaline and vector-change defibrillation ("Intervention Bundle") Drug component International Non-proprietary Name: Esmolol (esmolol hydrochloride) Dose: 50 mg bolus, each dose followed by a 10 mL 0.9% sodium chloride flush Maximum total dose during the study intervention window: 100 mg (two 50 mg boluses) Mode of administration: Intravenous (IV) or intraosseous (IO) bolus Schedule: Dose 1 immediately after randomisation to the intervention arm; Dose 2 administered if the patient remains in VF/VT 4 minutes after Dose 1 Duration of administration: A single 10-minute intervention window from the point of randomisation Non-drug components of the bundle Cessation of adrenaline – No further 1 mg adrenaline boluses are administered by the prehospital team during the 10-minute intervention window. If the patient achieves ROSC and subsequently re-arrests in VF/VT during the window, the second esmolol dose may be administered at the discretion of the treating clinicians; adrenaline remains withheld for the duration of the window. Vector-change defibrillation – Defibrillation pads are repositioned to an anterior–posterior configuration after the three unsuccessful shocks that establish eligibility (if not already in this position). Vector change is included in both arms, consistent with current Australia and New Zealand Committee on Resuscitation (ANZCOR) guidance for persistent shockable rhythms, and is therefore not unique to the intervention arm; it is described here for completeness of the bundle as delivered. Standard Advanced Life Support (ALS) continues throughout: high-quality manual or mechanical chest compressions (LUCAS 3 [Stryker] or Corpuls CPR [GS Elektromedizinische Geräte] where available), advanced airway management with waveform capnography, IV/IO access, amiodarone per ANZCOR ALS, and ongoing rhythm checks and defibrillation at standard 2-minute intervals. Reversion to standard ALS – If the patient remains in persistent VF/VT 10 minutes after randomisation (i.e. after 5 cycles and 2 esmolol doses), the treating team reverts to standard ALS and may employ any further measures within their routine scope of practice, including transport to hospital. In-hospital management is at the discretion of the receiving team and is not constrained by the study protocol; beta-blockade in hospital is permitted if clinically indicated. Materials used in intervention delivery Pre-prepared esmolol 50 mg ampoules (or equivalent presentation) carried on Intensive Care Paramedic (ICP) response vehicles Sequentially numbered, opaque, sealed envelopes (SNOSE) for allocation concealment — foil-lined to prevent transillumination and tamper-signed across the seal — stored on each ICP response vehicle Study-specific case report forms (paper and/or electronic) A laminated on-scene infographic summarising the post-randomisation algorithm for both arms Standardised training materials (see "Training" below) Who delivers the intervention The intervention is delivered by South Australian Ambulance Service (SAAS) Intensive Care Paramedics (ICPs). ICPs are advanced-practice paramedics qualified to deliver critical care interventions including advanced airway management, vasoactive and antiarrhythmic drug administration, and resuscitation team leadership. SAAS dispatch protocol mandates the attendance of at least one ICP at every cardiac arrest within the Adelaide metropolitan area. Only ICPs who have completed the study-specific training package may recruit, randomise, and deliver the intervention. Mode of delivery Face-to-face, individually delivered, in the prehospital out-of-hospital environment at the scene of the cardiac arrest. The intervention is delivered once per eligible patient. Number of sessions, schedule, intensity A single intervention episode per participant. The intervention period spans 10 minutes from the point of randomisation, during which up to two 50 mg esmolol doses (4 minutes apart) are administered. Total study-specified intervention time is therefore 10 minutes; no further study-mandated interventions occur after this window. Location Wherever an eligible Out of Hospital Cardiac Arrest (OHCA) occurs within the Adelaide metropolitan area served by SAAS Metro North, East, South, and West sectors — typically the patient's home or a public place. The intervention is delivered on-scene; if extrication or transport is required, the intervention continues uninterrupted where operationally feasible. Tailoring/personalisation The intervention is delivered to a fixed protocol and is not titrated to individual patient characteristics. The only protocol-permitted variation is the discretionary administration of the second esmolol dose if a patient continues to experience persistent VF/VT cardiac arrest within the 10-minute window, as described above. Concurrent ALS care (e.g. airway choice, mechanical CPR device, fluid administration) remains at the discretion of the treating ICP within SAAS scope of practice. Training of intervention providers Prior to recruitment commencement, all participating ICPs across the four metropolitan sub-sites will complete a standardised study education package covering: study rationale, inclusion/exclusion criteria, the randomisation procedure (SNOSE), the intervention and standard-care algorithms, esmolol pharmacology and administration, data collection requirements, and consent/waiver-of-consent processes. Training will include didactic content and simulation-based practice. Pre- and post-training competency assessments will be administered, and clinician self-reported confidence/competence will be measured before and after training. Adherence/fidelity assessment Fidelity will be assessed as a primary feasibility outcome by the study team. Indicators include: Proportion of intervention-arm participants receiving the full bundle (cessation of adrenaline, esmolol dose 1, vector-change defibrillation, and esmolol dose 2 where indicated) Proportion of standard-care participants in whom no beta-blocker was administered during the prehospital phase Proportion of recruited participants in whom randomisation was completed at point of care without protocol deviation Completeness of case report form data at each predefined time point Qualitative narrative from participating ICPs regarding barriers to recruitment, randomisation, and protocol adherence, captured via retrospective case review and post-case debriefing The pre-specified progression threshold is greater than or equal to 80% protocol adherence in each arm, averaged across the four sub-sites. Strategies to maintain fidelity include the on-scene infographic, ongoing refresher training, regular feedback to ICP teams on aggregate adherence data, and individual case review with treating clinicians where deviations occur.