{"id":"10/134/06","award_type":"Research","award_title":"Protocolised trial of invasive and non-invasive weaning off ventilation","award_amount":1192962.9,"award_amount_disp":"1,192,962.91","app_abstract":"Approximately 60,000 people each year in the UK become critically ill and require sedation and treatment with invasive mechanical ventilation given via a tube placed in the windpipe.  Although initially life saving, invasive mechanical ventilation is associated with a number of complications including ventilator associated pneumonia and prolonged requirements for sedatives with weakening of the leg, arm and breathing muscles.  The longer a person requires invasive ventilation the poorer their chances of surviving.  The process of liberating patients from invasive ventilation is referred to as weaning.  Previous research from our team has shown that implementing protocols for weaning can reduce the amount of time on a ventilator machine.  There is also evidence that switching from invasive to non-invasive ventilation (also called mask ventilation) as an intermediate step in the weaning process may reduce the amount of time spent on the ventilator and complications.  This study will compare protocolised invasive (tube) and non-invasive (mask) weaning strategies.    Patients will be assessed daily for their readiness to commence weaning using a system we have previously developed and tested.  Those ready for weaning will be allocated (randomised) to either a protocolised weaning pathway that includes a period of mask ventilation or a protocolised pathway that does not include mask ventilation.  The study will measure the cost effectiveness and health benefits (time spent on a ventilator; survival, time spent in hospital including intensive care, complication rates) of each approach. We will include an internal pilot to ensure that recruitment, randomisation, treatment, and follow-up assessments all run smoothly.     The Intensive Care Outcomes Network emphasises the impact of critical illness and its treatments on health related quality of life.  Feedback from users as part of this application highlight that the weaning process can be traumatic for patients and their relatives. The study will measure the impact of each approach on health related quality of life using validated questionnaires and qualitative research methods to highlight the patient experience.       Weaning is a complex intervention with several interacting components.  These include (but are not limited to) standardisation of design and deliver of the intervention, overlap between weaning strategy and the effects of sedation, logistical considerations, organisational culture (the way doctors/nurses and hospitals work).  Our approach will be guided by the MRC best practice framework for complex interventions. 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.  This will aid implementation of the findings of the trial into UK clinical practice.       We have pulled together with a strong track record of successful collaboration which includes many of the large studies completed in critical care to date (BALTI-2 study; BALTI-prevention; OSCAR trial; ICON study; SWIFT study).  We will work in partnership with our network of critical care unit with established track records of recruiting to critical care trials.  This team has the professional support of the Intensive Care Society (UK) and British Thoracic Society Critical Care Group.   The teams expertise includes senior clinical trialists (Lamb (NIHR Senior Investigator); Gates); health economists (Petrou) authors of the Cochrane review on protocolised weaning (Blackwood) and clinician scientists (Perkins, McAuley, Gould, Young).","app_plain_english_summary":"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 trial    Health 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.","headline":"A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation, although there were other possible advantages for patients.","hrcs_health_category":["Respiratory"],"rac_code":["7.3 Management and decision making"],"research_type":"Primary Research","programme":"Health Technology Assessment","funding_stream":"HTA Commissioned","award_status":"Completed","programme_stream":"Commissioned","contracting_org":"Heart of England NHS Foundation Trust","centre":"NETSCC","contracting_org_title":"Contracting Organisation","start_date":"2013-01-01T23:59:59.000+0000","end_date":"2017-07-31T23:59:59.000+0000","pub_date":"2019-09-18T23:59:59.000+0000","lead_investigator_title":"Chief Investigator","lead_investigator_name":["Professor Gavin Perkins"],"lead_investigator_orcid":["0000-0003-3027-7548"],"co_investigator_name":["Dr Tim Gould","Professor Bronagh Blackwood","Professor Danny McAuley","Professor Duncan Young","Professor Fang Gao","Professor Louise Rose","Professor Nicholas Hart","Professor Sarah Lamb","Professor Simon Gates","Professor Stavros Petrou","Professor Timothy Walsh"],"co_investigator_orcid":["","0000-0002-4583-5381","0000-0002-3283-1947","0000-0002-6838-4835","0000-0002-8095-0609","0000-0003-1700-3972","0000-0002-6863-585X","0000-0003-4349-7195","0000-0003-3193-0975","0000-0003-3121-6050","0000-0002-3590-8540"],"research_call":"Clinical and cost effectiveness of using non-invasive ventilation to wean patients off invasive ventilation","call_id":"10/134","link_type":["Clinical Trials Registry"],"link_title":["ISRCTN Registry"],"link_URL":["http://www.isrctn.com/ISRCTN15635197"],"link_group":["Overview"],"link_date_year":[0],"link_date":["1900-01-01T23:59:59.000+0000"],"award_website":"","funder":"NIHR (non-ODA)","reg_number_title":["ISRCTN"],"reg_number":["15635197"],"reg_number_url":["http://www.isrctn.com/ISRCTN15635197"],"additional_funder":"","jl_rep_id":"https://doi.org/10.3310/hta23480","jl_rep_title":"Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care: the Breathe RCT","jl_rep_pub_date":"2019-09-18T23:59:59.000+0000","doc_type":["CommsBrief","Protocol"],"doc_group":["Background","Methods"],"doc_title":["Commissioning Brief","Protocol"],"doc_URL":["https://njl-admin.nihr.ac.uk/document/download/2023091","https://njl-admin.nihr.ac.uk/document/download/2024346"],"doc_date":["2011-01-07T23:59:59.000+0000","2015-12-07T23:59:59.000+0000"],"doc_date_year":[2011,2015],"doc_ver":["V10","V20"],"highlighting":"","full_contracting_org":"Heart of England NHS Foundation Trust","_version_":1875670583892508672,"full_co_investigator_name":["Dr Tim Gould","Professor Bronagh Blackwood","Professor Danny McAuley","Professor Duncan Young","Professor Fang Gao","Professor Louise Rose","Professor Nicholas Hart","Professor Sarah Lamb","Professor Simon Gates","Professor Stavros Petrou","Professor Timothy Walsh"],"start_year":2013,"full_lead_investigator_name":["Professor Gavin Perkins"]}