Approved Device for Stroke-Related Dysphagia Enters an RCT

ABU DHABI, UAE — A device characterized by the US Food and Drug Administration as safe for the treatment of dysphagia following acute stroke is finally being tested for efficacy in a randomized controlled trial (RCT) of sufficient size to determine whether it should be a standard of care.

Currently, “there are no proven therapies for acute stroke dysphagia beyond behavioral training,” said study investigator Philip M. Bath, DSc, professor of stroke medicine, University of Nottingham, Nottingham, England.

For a complication that occurs in up to 60% patients admitted to a hospital for acute stroke and a risk factor for worse stroke outcomes, dysphagia is an often-overlooked source of major post-stroke morbidity, said Bath. He added the lack of a well-validated trial for a pharyngeal electrical stimulation (PES) device is a major unmet need.

There is evidence of benefit from the device, but just not from an RCT, said Bath, who provided preliminary results of a new ongoing multicenter trial as a late-breaking abstract on October 25 at the 16th World Stroke Congress (WSC) 2024.

Although a PES (Phagenyx) has been available in the United States for the treatment of neurogenic dysphagia since 2020, the absence of an RCT explains why it is still not available in many countries, including the United Kingdom. Bath said the UK’s NICE guidelines disallow PES outside of an RCT.

So far, the PhEAST trial includes 36 sites in the United Kingdom, and 280 acute stroke patients with severe dysphagia have been enrolled. This is more than one third of the 800 planned. An expansion of trial sites through Europe was initially thwarted by Brexit, said Bath, but he added that negotiations to add sites in Ireland, Europe, Australia, and elsewhere are ongoing.

In this trial, patients are randomly assigned to PES for 6 days plus standard care, which includes behavioral therapy, or to standard care alone. The primary endpoint is the ability to return to oral intake of food and drink as defined by the Dysphagia Severity Rating Scale (DSRS). The assessors are blinded to the assigned treatment group.

Patients can be enrolled in the trial 4-21 days after an ischemic or hemorrhagic stroke involving either the posterior or anterior circulation.

So far, patients have been enrolled on average 15 days after stroke. Of these, 18% had hemorrhagic stroke. The mean age at the time of enrollment was 75 years. Forty percent are women. The median DSRS score is 12, signifying complete dependence on tube feeding. The median National Institutes of Health Stroke Scale (NIHSS) score is 13.

“An NIHSS score of 13 doesn’t sound severe, but this is not a score of 13 at 4 days, this is 13 at 15 days post-stroke, so these are very severe stroke patients,” Bath said.

A 50% Drop in DSRS

Preliminary data show that so far, at follow-up there has been no change in the modified Rankin Scale score. The Barthel Index increased modestly, climbing from a baseline of 15 points to 21 points, but the median DSRS score has dropped from 12 to 7.

The nearly 50% reduction in the DSRS score is an encouraging signal of a therapeutic effect, according to Bath, but he said the degree to which his reduction can be attributed to the device awaits a full analysis performed when the target enrollment is reached.

The PES device employed in the PhEAST trial, which is the same as the one currently available in the United States, includes a base station and a nasogastric (NG) tube equipped with electrical rings to stimulate the nerves as the tube descends the upper gastrointestinal tract. The device is used for 10 minutes per day.

The tube in the PES device functions like any other NG tube for delivering nutrition, according to Bath. There have been no serious device-related adverse events.

The strongest previous support for benefit from PES comes from a 2020 observational single-arm cohort study called PHADER. The majority of the 255 enrolled patients had acute stroke, but those with neurogenic dysphagia from other etiologies were also included. PES was associated with not only significant reduction in dysphagia on the basis of the DSRS but also improvement in penetration-aspiration scale scores.

In a 2024 meta-analysis of six PES studies (341 participants) conducted between 2010 and 2018, there was a significant advantage for the device over control (P = .02) overall, but not all of the studies showed a significant advantage on their own, said Bath.

A 162-patient RCT of PES led by Bath 8 years ago was negative, but he believes that the electrical stimulation of 18 milliamps used in that study was insufficient. In the PhEAST trial, the stimulation levels have been increased to 32.5 milliamps.

Calling this “excellent work,” P. N. Sylaja, MD, professor of neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India, agreed that there is an unmet need for management of dysphagia after an acute stroke.

However, as moderator of the late breaker session where the data were presented, she expressed concern about how the NG tube is tolerated, based on her assumption that it is larger than typical NG tubes.

While Bath acknowledged that the diameter of the tube is greater than that of contemporary NG tubes, he said the size of the PES tube is similar to that of older generation tubes. Overall, he called the NG tube–related side effects in his experience and in follow-up in the new trial “no different” than those encountered with NG tubes in general.

The PhEAST trial is receiving support from Phagenesis Ltd., the company that produces the PES device being employed in the PhEAST trial. Bath reported a financial relationship with Phagenesis as well as CoMind, DiaMedica Therapeutics, and Roche. Sylaja reported no relevant financial relationships.