Title: Pharyngeal Electrical stimulation for Acute Stroke dysphagia Trial (PhEAST)
Funder: Department of Health and Social Care

Abstract: Aims_x000D_ To see if electrical stimulation of the back of the throat (pharyngeal electrical stimulation, PES) reduces swallowing problems (dysphagia) after stroke._x000D_ _x000D_ Background_x000D_ Stroke (brain attack) is common and complicated by swallowing problems in half of patients, many of whom still have abnormal swallowing a year later. Swallowing problems lead to chest infections, poor nutrition, the need for a feeding tube inserted into the stomach, long hospital stays, disability and so nursing home care after hospital, and death. Patients dislike not being able to eat and drink normally and having a long term feeding tube. These reduce quality of life and add to the physical, mental, emotional and financial cost of stroke. Currently, there are no proven treatments for swallowing problems after stroke._x000D_ _x000D_ The control of swallowing uses nerves running between the back of the throat and the brain. Stimulating these nerves with a tiny electric current re-programmes the swallowing centres in the brain. PES is given via a tube inserted through the nose to the back of the throat, and stimulation can barely be felt. In small and medium-sized trials, PES was safe and tolerated, and reduced swallowing problems (assessed using a scale called the ‘dysphagia severity rating scale’ and x-ray evidence of measuring liquid entering the airway). Good results have also been seen in patients with other brain problems and abnormal swallowing. Our proposed large trial will learn from the previous studies to maximise the chance of finding a positive treatment effect and avoid earlier sub-optimal study designs._x000D_ _x000D_ Design and methods (How we will do the study)_x000D_ We would like to do a large and simple trial of PES in 800 patients with recent stroke and needing a feeding tube because of poor swallowing. 50 sites in 4 countries (UK, Austria, Denmark, Germany) will recruit patients. Following consent, people will be allocated at random (like toss of a coin) to either electrical stimulation via a treatment catheter, or to continue with their normal feeding tube. Treatment will be given for six days by a specially trained researcher, nurse, therapist or doctor. The main outcome will be improvement in swallowing using the dysphagia severity rating scale two weeks after starting treatment. We will also measure pneumonia, antibiotic usage, continued need for a feeding tube, disability, quality of life, mood and death. The cost of the treatment against the cost-savings from potentially improved swallowing and reduced stay in hospital will be assessed using health economic analyses. If PES improves swallowing, reduces pneumonia and is cost effective, then it could be used widely after stroke in people with swallowing problems._x000D_ _x000D_ Patient and public involvement_x000D_ A PPI member is a grant applicant and has helped with the trial design and grant writing. He will lead on writing the participant and family-facing materials, including information sheets, consent forms, website and training materials. At trial end, he will lead on PPI publicity of the results. A second PPI member will sit as an independent member of the Trials Steering Committee._x000D_ _x000D_ Dissemination (How we will spread the results)_x000D_ Results will be presented at international stroke conferences, in leading medical journals, via social media and the trial web site, and to stroke survivors and public, including the Stroke Assembly Lay conference in the UK and via the Stroke Alliance For Europe (SAFE) network.

Lay abstract: Research question_x000D_ Does pharyngeal electrical stimulation (PES) reduce dysphagia after stroke and is it safe and cost effective?_x000D_ _x000D_ Background_x000D_ Acute stroke (ischaemic, haemorrhagic) is common and complicated by oropharyngeal dysphagia in at least 50% of patients, many of whom remain dysphagic at one year. Dysphagia often requires enteral feeding and is complicated by aspiration/pneumonia, malnutrition, prolonged hospital stay, institutional care after hospital and death. Hence, it adds considerably to the physical, emotional and financial costs of stroke, delays discharge from hospital, and adds to health service usage and institutional burden. There are no definitive treatments for post-stroke dysphagia._x000D_ _x000D_ Pharyngeal electrical stimulation (PES) increases afferent feedback from the pharynx to brain via bulbar cranial nerves and can drive long-term beneficial plasticity in cortical swallowing control. In phase II trials, PES was safe and well tolerated, and reduced clinical dysphagia (assessed using the validated dysphagia severity rating scale, DSRS), radiological aspiration, and length of stay in hospital in dysphagic patients after stroke. PES also facilitated decannulation in intubated stroke patients in phase II and III trials and improved dysphagia in a small trial in multiple sclerosis. The single-arm PHADER study showed that PES improved DSRS and instrumentally-assessed aspiration in patients with neurogenic dysphagia, including those with stroke. Whilst the evidence of beneficial effects of PES on neurogenic dysphagia is mounting, there remains uncertainty over its effectiveness in non-ventilated stroke patients._x000D_ _x000D_ Aims/objectives: In comparison with usual care:_x000D_ - Primary: Does PES reduce dysphagia assessed using the DSRS?_x000D_ - Secondary: What subgroups predict DSRS response to PES? Does PES reduce hospital length of stay, pneumonia, antibiotic exposure and dependency, and increase quality of life and activities of daily living? Is PES cost effective?_x000D_ _x000D_ Methods_x000D_ We propose to do a large streamlined international (UK, Austria, Denmark, Germany) prospective randomised open-label blinded-endpoint phase IV trial of PES in 800 dysphagic patients with recent stroke. Patients with severe dysphagia within 4-31 days of stroke onset will be recruited. Following consent and randomisation, PES catheters will be inserted in active group participants and six days of treatment administered by a PES-trained research coordinator, nurse, speech therapist or medic. Control participants will receive standard-of-care with no PES catheter. The primary outcome is DSRS at 2 weeks post start of treatment. Secondary outcomes include hospital length of stay; dysphagia, dependency, disability, quality of life, pneumonia, need for feeding tube, death at 3 months; death at 1 year; and health economics. We will embed a Study Within A Trial (SWAT) aimed at maximising PES treatment current._x000D_ _x000D_ Timelines for delivery_x000D_ The grant will last 39 months. 400 participants will receive PES in addition to standard-of-care and 400 standard-of-care alone, with groups followed to day 90, and death to one year._x000D_ _x000D_ Impact and dissemination_x000D_ Although PES has a CE mark, the absence of definitive large trial data are limiting its use. If PES reduces dysphagia cost-effectively, it could be introduced rapidly across UK/European stroke units. Positive results will lead to multiple presentations/publications, considerable media coverage, and changes in clinical guidelines.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: ORAL AND GASTROINTESTINAL;STROKE