Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Open, multi-centre, randomised controlled trial of cardiac output -guided haemodynamic therapy compared to usual care in patients undergoing emergency bowel surgery. This project is funded by the National Institute for Health Research Health Technology Assessment programme (project number 15/80/54) Background – Emergency Laparotomy burden High incidence (30,000 cases/yr UK) X High mortality (20% @ 90-day in >50yrs) = Many lives saved if treatments with modest mortality benefit are routinely adopted …though showing modest effect size = very large trial! Background – candidate treatment Perioperative cardiac output-guided haemodynamic therapy MORTALITY: Risk Ratio 0.86 [0.74-1.00] Pearse et al. JAMA 2014; 311: 2181-90. Background – candidate treatment Perioperative cardiac output-guided haemodynamic therapy However: VERY few emergency laparotomy patients studied Elective Elective surgery GDHT ≠ Emergency Emergency laparotomy GDHT? Critical care GDHT Background – current practice, equipoise? COM-based GDT NELA Centre “other” GDT NELA: -Cardiac output monitor in 39% -Limited evidence base NOT an audit standard FLO-ELA clinician survey 2016: -137 respondents -85% willing to randomise % of cases with GDT Background – potential trial funding? “Efficient Study Designs” call: …particular design features – more rapid conduct, lower costs or both – but giving sufficiently robust data… …the use of routinely collected data… …simple randomised trials… focusing on a limited number of the most important outcomes… A unique opportunity? Indisputable healthcare need Prioritisation by clinicians and public (JLA) Hopeful intervention with clinician equipoise NELA FLO-ELA NIHR HTA Efficient Study Designs Delivery infrastructure: POM-CTN, NIHR CRN, trainee networks Design Pragmatic multicentre open randomised trial supported by data from the ongoing National Emergency Laparotomy Audit (NELA). Recruitment support and local monitoring from research nurses, “real world” intervention delivery by clinicians. • Inclusion criteria: Patients aged 50+ requiring emergency bowel surgery in line with NELA criteria – with/without capacity • Exclusion criteria: Patient or clinician refusal Design • Intervention: cardiac output monitoring to determine the dose & timing of intravenous fluid administration according to a suggested algorithm, during and up to six hours after emergency laparotomy. Clinician discretion on choice of cardiac output monitor shown to accurately track stroke volume changes and of isotonic fluid type for boluses. • Control group: Intravenous fluid administration without the use of cardiac output monitoring or algorithm. Basic standards of care set for both groups Design • Primary outcome: mortality 90 days after surgery • Secondary outcomes: 1-yr mortality, critical care and hospital LoS, cost effectiveness • Sample size: 7646 patients (3823 per group) to detect an absolute reduction in mortality at 90-days from 19% to 16% with 90% power • Sites and recruitment: 100 UK sites taking part in NELA, recruitment over three years from mid 2017. Efficiencies • NELA & NHS Digital for all patient and outcome data • Minimal supplementary data fields to track intervention • Reduced research staff requirement • Research active trainees and consultants support recruitment – track record • Clinicians deliver intervention – familiarity • Industry support for intervention costs Centres and Recruitment 100% of target 80% of target Total centres open 10000 120 9603 9000 100 Patients recruited 8000 7682 7000 80 6000 5000 60 4000 40 3000 2000 20 1000 0 0 0 5 10 15 20 25 Recruitment month 30 35 40 Key challenges 1: delivering recruitment • Lots of eligible patients (~25,000/yr across NELA) • Within 100 of 192 NELA centres, recruiting 30% of this group for 3yrs = sample size achieved • Strong track record: • • • • EPOCH as “NELA + trial” model OPTIMISE as large contemporary GDHT trial Trainees as capable of supporting / delivering RCTs Recruiting critically ill patients +/- capacity at all hours to large RCTs • POM-CTN adoption & NELA network to engage local teams Key challenges 2: protocol compliance • Vital to maintain separation between control/intervention group despite pragmatic design • Individual clinician equipoise a prerequisite to randomisation • Monitoring, feedback and management of protocol adherence / contamination – including removal of sites with poor compliance rates Managing the risk – feasibility phase • First year of recruitment to look at: Sites opening, recruitment rates, adherence and contamination • Targets: • 90-100 sites open and recruiting • >80% of predicted recruitment • <10% protocol deviations FLO-ELA local Principal Investigators – key roles • Champion to clinical teams • Gather a team covering surgery, anaesthesia, critical care • Establish working practices – trainees and front line on call teams – round the clock recruitment • Encourage equipoise • Support rapid site set-up • Recruit average 3-4 patients per site per month when established (2-3 in hours, 1-2 out of hours) • Ensure protocol compliance Support for participating centres • Funded research nurse time • NIHR Portfolio Band 3 tariff • Support from industry • Simple design – non-CTIMP, no extensive intervention or complex outcomes follow-up for research team Conclusion • An exciting and unique opportunity to guide clinical practice on a key intervention • Large pragmatic design – great community and network support is vital • Watch this space! @FLOELAtrial Chief Investigator: Mark Edwards (Consultant in Anaesthesia & Perioperative Medicine, Honorary Senior Clinical Lecturer, Southampton) [email protected] - @dr_mark_edwards Senior Co-investigators: Mike Grocott, Rupert Pearse Trial team: Monty Mythen, Dion Morton, NELA team (Dave Murray and Iain Anderson), QMUL Pragmatic Clinical Trials Unit (Brennan Kahan, Anita Patel (Health Ec), Ann Thomson), Trainee networks (Ben Harris, Marianne Johnstone), Keith Young (lay representative)