Title: Protocolised trial of invasive and non-invasive weaning off ventilation
Funder: Department of Health (England)

Abstract: Design: Multicentre pragmatic randomised controlled trial with internal pilot. Randomisation will be minimised by recruitment centre; presence of chronic obstructive pulmonary disease and operative / non-operative admission. Setting: Twenty-five large adult ICUs with a strong track record of successful recruitment to clinical trials and with a patient case mix typical of UK critical care practice.Target Population: Inclusion criteria will be adult patients with respiratory failure who have received invasive ventilation for more than 48 hours (from the time of intubation) and fail a spontaneous breathing trial (SBT). Exclusion criteria include (1) presence of tracheostomy (2) profound neurological deficit (3) any absolute contraindication to NIV (4) home ventilation prior to ICU admission (5) decision not to re-intubate or withdrawal of care anticipated (6) further surgery / procedure requiring sedation planned in next 48 hours (7) previous participation in the trialHealth Technology: Our Cochrane review (Blackwood 2011) of protocolised weaning failed to identify a single optimal protocolised weaning strategy that could be used unchanged in the control arm and modified with NIV in the treatment arm. Current UK guidelines (ICS 2007) recommend sequential reductions in inspiratory pressure support ventilation (IPS) titrated according to physiological response. Patients randomised to the treatment arm will continue with sequential reductions in pressure support until a priori defined parameters are reached suitable for early extubation (have their endotracheal tube removed) and switch to pressure supported breaths through a mask (NIV). NIV weaning will occur through progressive increments of time off NIV titrated to defined physiological parameters until they are weaned and stable at which point their NIV will be stopped. Patients randomised to protocolised invasive weaning arm will continue with sequential reductions in pressure support titrated according to defined physiological parameters until they are weaned and stable at which point they will be extubated. We will engage the intensive care community from the start of this project by hosting a weaning workshop at our annual scientific meeting. We have designed the weaning protocols to fit UK ICU culture and practice. We will pre-pilot and if necessary refine the weaning protocols prior to commencement of the trial.Measurement of outcomes and cost: The primary clinical effectiveness outcome will be time from randomisation to liberation from ventilation . Secondary outcomes: 30 90 and 180 day all cause mortality; duration of invasive mechanical ventilation (IMV) from and total ventilator days (invasive and non-invasive ventilation); time to meeting ICU discharge criteria; hospital length of stay; proportion of patients receiving antibiotics for presumed respiratory infection; respiratory and total antibiotic days; re-intubation; placement of tracheostomy; adverse events health related quality of life(EQ-5D and SF12). Predefined subgroup analyses will comprise (1) responsibility for weanign processes (2) presence/absence of COPD (3) operative / non-operative indication for admission.Given the uncertainty surrounding the potential costs and health consequences of NIV facilitated weaning we include a full economic evaluation. The economic evaluation will be from the NHS and personal social services perspective. Resource utilisation from randomisation to six months will be captured on data collection forms and through economic questionnaires. Current UK unit costs will be applied to each resource item to value total resource use.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: RESPIRATORY