Paramedics are giving thousands of cardiac arrest patients either adrenaline or a saltwater placebo in a double-blind trial to settle a decades-old question about whether the drug actually helps people survive. Adrenaline has been standard treatment for cardiac arrest for over a century, but the evidence supporting it is weak—animal studies and small human trials suggest it may restart the heart but also damage the brain by reducing blood flow to delicate tissues. If the trial shows adrenaline improves survival without causing severe neurological harm, it will confirm current practice and justify continued use. If it does not, or if survivors end up with worse brain function, the findings could force a major shift in resuscitation protocols worldwide, potentially sparing thousands of patients from futile treatment that leaves them alive but severely disabled. The results will also inform ambulance services and the NHS about whether the drug is cost-effective, influencing training, drug procurement, and clinical guidelines for prehospital emergency care.
View original technical description
OVERVIEW: This proposal is for a pragmatic, randomised, double blind, placebo controlled trial to determine if, in adults with out of hospital cardiac arrest (OHCA), treatment with intravenous adrenaline compared to placebo improves 30 day survival and other clinical, patient focused and economic outcomes. DESIGN: Double blind, individual patient randomised placebo controlled trial with internal pilot study. The internal pilot (6 months duration) will test that the components of this new study work together effectively (i.e. recruitment rate, compliance with allocated intervention and data collection and follow-up). SETTING: Prehospital care. Five NHS Ambulance Services Trusts have obtained Board approval to participate (London, South Central, North East, Welsh and West Midlands). TARGET POPULATION: Patients with out of hospital cardiac arrest (OHCA) in whom resuscitation is attempted. INCLUSION CRITERIA: Patients will be enrolled if they meet the following criteria (1) out of hospital cardiac arrest (2) Advanced life support initiated and/or continued by ambulance service clinician. EXCLUSION CRITERIA: (1) Known or appear pregnant (2) Known or appear to be aged under 16 (3) Cardiac arrest secondary to anaphylaxis or life-threatening asthma (4) Adrenaline given prior to arrival of ambulance service clinician HEALTH TECHNOLOGY BEING ASSESSED: Intravenous adrenaline compared to placebo. MEASUREMENT OF COST AND OUTCOME: Primary clinical outcome: Survival to 30 days post-cardiac arrest. Secondary clinical outcomes: Survived event (return of spontaneous circulation (ROSC) on arrival at hospital); survival and neurological status at hospital discharge, 3 months and 6 months; hospital length of stay; intensive care length of stay. Patient focused secondary outcomes: Health related quality of life (SF-12 and EQ-5D-5L) at 3 and 6 months; cognition (mini mental state examination (MMSE), IQCODE and “Two Simple Questions”); post-traumatic stress (PTSD civilian checklist (PCL-C)); anxiety and depression (Hospital Anxiety and Depression Scale (HADS)) at 3 months. Primary economic outcome: Incremental cost per quality-adjusted life year (QALY) gained from the perspective of the NHS and personal social services (PSS). Secondary economic outcomes: Cost of critical care stay (level 2/3 days); cost of hospital stay; utilisation of NHS and PSS resources after discharge; broader resource utilisation after discharge. Neurological outcome: We will measure the Modified Rankin Score (mRS) at hospital discharge, 3 and 6 months. We selected mRS over Cerebral Performance Category as it is more sensitive to detect mild cognitive impairment, it can be reliably extracted from medical records and is a predictor of long term survival. There is emerging international consensus (Utstein 2012/13) that mRS should be the primary measure of neurological outcome in cardiac arrest trials. MRS is a 7 point scale ranging mRS 0 (no symptoms) to 6 (dead). Other functional outcomes and health related quality of life: We will assess cognitive function using mini-mental state examination(MMSE), the informant questionnaire cognitive decline evaluation (IQCODE) and the two simple questions tool as supplementary assessments of cognitive function. The presence of post traumatic stress disorder and depression will be measured by the PTSD Civilian Checklist (PCL-C) and Hospital Anxiety and Depression Scale (HADS). Two of these measures (PCL-C and HADS) are being used as part of a multi-centre follow-up for people surviving a critical illness (Intensive Care Outcome Network study) which can be used as a reference population. The SF-12 and EQ-5D-5L will be used to the measure health-related quality of life of survivors. SAMPLE SIZE: We propose a sample size of 8,000. This will have 90% power to achieve a statistically significant (p<0.05) result if the true treatment difference is a risk ratio of 1.33 (2% change in 30
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know