Interventional procedure overview of pharyngeal electrical stimulation for neurogenic dysphagia
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Summary of key evidence on pharyngeal electrical stimulation for neurogenic dysphagia
Study 1 Speyer R (2022)
Study type | Systematic review and meta-analysis |
|---|---|
Country | Not reported for individual studies |
Recruitment period | Not reported for individual studies |
Study population and number | n=10 studies, 428 people (252 active treatment), 5 studies were included in the meta-analysis People with neurogenic dysphagia. |
Age and sex | Mean 64.7 years; 56.7% male |
Patient selection criteria | Inclusion criteria:
Exclusion criteria: non-electrical peripheral stimulation (for example air-puff or gustatory stimulation), pharmacological interventions and acupuncture, invasive techniques and/or those that did not specifically target oropharyngeal dysphagia (for example, deep-brain stimulation studies after neurosurgical implementation of a neurostimulator), conference abstracts, doctoral theses, editorials, and reviews were excluded. |
Technique | PES. Typically delivered as 10-minute stimulation over 1 to 5 days (varying between studies). |
Follow up | Not reported for individual studies |
Conflict of interest/source of funding | Conflict of interest: The authors disclose no conflict of interest, however, 1 author is the co-founder of Phagenesis, the manufacturer of a PES device. Source of funding: No external funding was received. |
Analysis
Study design issues: This systematic review and meta-analysis assessed the efficacy of PES for people with oropharyngeal dysphagia. The methods and reporting of the systematic review were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed by the Cochrane Risk of Bias 2 (RoB 2) tool. The overall risk of bias for PES studies was assessed as 'low risk' for 6 studies and 'some concerns' for 4 studies. Five studies were included in the meta-analysis for PES, reasons for exclusion were given for 3 studies: overlap in population between studies, insufficient data for meta-analyses, and no confirmation of dysphagia diagnosis prior to treatment. It is not reported for which studies these reasons relate to.
Two meta-analyses were conducted to compare:
pre-post outcome measures of dysphagia.
mean difference between neurostimulation and comparison controls in outcome measures from pre- to post-intervention.
Effect sizes were calculated using a random-effects model were generated using the Hedges' g formula for standardised mean difference with a 95% CI. Effects sizes were interpreted using Cohen's d convention as follows: g ≤ 0.2 as no or negligible effect; 0.2 < g ≤ 0.5 as small effect; 0.5 < g ≤ 0.8 as moderate effect; and g > 0.8 as large effect. Heterogeneity was estimated using the Q statistic. I2-values of less than 50%, 50% to 74%, and higher than 75% denote low, moderate, and high heterogeneity, respectively. Publication bias was also assessed, and the authors concluded that there was no evidence of publication bias.
Study population issues: all studies included in the meta-analyses included people with post-stroke dysphagia.
Key efficacy findings
Pre-post meta-analysis
Number of people analysed: 5 studies
Five studies using PAS to assess dysphagia were included in the meta-analysis.
The pre-post intervention effect sizes for the included studies ranged from 0.265 (small effect) to 0.802 (large effect), with a statistically significant overall moderate effect size of 0.527 (z(4)=3.983, p=0.000, 95% CI 0.268 to 0.786).
Between group meta-analysis
Number of people analysed: 5 studies
Five studies using PAS to assess dysphagia were included in the meta-analysis.
There was no statistically significant difference in PAS scores between PES and sham groups (z(4)=0.718, p=0.473, Hedges' g=0.099, and 95% CI -0.170 to 0.368), suggesting no improvement in PAS outcomes following PES neurostimulation versus sham.
Key safety findings
Safety findings were not reported.
Study 2 Cheng I (2021)
Study details
Study type | Systematic review and meta-analysis |
Country | Not reported for individual studies |
Recruitment period | Not reported for individual studies |
Study population and number | n=8 studies, 334 people (187 active treatment) People with post-stroke neurogenic dysphagia. |
Age and sex | Mean age of people in the studies ranged from 60.3 to 74.4; sex not reported |
Patient selection criteria | Inclusion criteria:
Exclusion criteria: Studies with people whose dysphagia was caused by other aetiologies, case studies, open-label studies, animal studies, observational studies, quasi-experimental studies, studies on healthy volunteers, studies that did not include original data, non-English studies. |
Technique | PES. 5 Hz, 75% tolerated threshold for 10 minutes over 1 or 3 days (varying between studies) |
Follow up | Perioperative to 3 months |
Conflict of interest/source of funding | Conflict of interest: Not reported, however, 1 author is the co-founder of Phagenesis, the manufacturer of a PES device. Source of funding: The authors declare no financial support. |
Analysis
Study design issues: This systematic review and meta-analysis assessed the efficacy of PES for people with post-stroke neurogenic dysphagia. The methods and reporting of the systematic review were based on the PRISMA statement. Study quality was assessed by the Cochrane RoB 2 tool. The authors note that there was insufficient information to determine the risk of selective reporting and other risks so these 2 aspects were not assessed. Most studies had low risk of bias in most aspects. The following studies were assessed as high risk of bias for the following domains: blinding of participants and personnel (Cabib, 2020; Jayasekeran, 2010; Vasant, 2016), incomplete outcome data (Bath, 2016). Three meta-analyses were conducted using PES studies:
Overall treatment effect vs. sham
Early (up to 2 weeks) effects vs. sham
Late (3 months or more) effects vs. sham
A weighted average of standardised mean difference across studies was computed using random effects model analysis. For the interpretation of effect sizes, standardised mean difference of 0.2 represented a small effect, 0.5 a moderate effect, and 0.8 a large effect. p<0.05 was considered statistically significant. Heterogeneity was assessed with Cochrane's Q statistic and I2 test in which heterogeneity was considered substantial with p<0.05 and I2 higher than 50%.
Key efficacy findings
Overall treatment effect meta-analysis
Number of people analysed: 8 studies
There was a statistically significant overall moderate effect size of PES compared to sham with substantial heterogeneity: SMD=0.68 (95% CI 0.22, 1.14; p=0.004; I2=65%; figure below).
As a sensitivity analysis, Bath, 2016 was removed from the analysis. This resulted in a statistically significant large effect size without substantial heterogeneity: SMD=0.83 (95% CI 0.43, 1.42; p<0.001; I2=34%).
Early treatment effect meta-analysis
Number of people analysed: 8 studies
There was a statistically significant overall moderate effect size of PES compared to sham with substantial heterogeneity: SMD=0.68 (95% CI 0.22, 1.14; p=0.004; I2=65%; figure below).
Late treatment effect meta-analysis
Number of people analysed: 2 studies
There was no statistically significant effect size of PES compared to sham with no heterogeneity: SMD=−0.04 (95% CI −0.46, 0.38; p=0.86; I2=0).
Key safety findings
Safety findings were not reported.
Study 3 Bath PM (2016)
Study details
Study type | Multicentre, double-blinded (patients, assessors), sham-controlled RCT |
Country | Denmark, France, Germany, Spain, and the UK |
Recruitment period | 2012 to 2014 |
Study population and number | n=162 (87 active treatment) People with recent stroke and videofluoroscopy-confirmed dysphagia |
Age and sex | Mean (all randomised) 74.0 years; 55.2% male |
Patient selection criteria | Inclusion criteria: people who were admitted to hospital with a clinical stroke syndrome because of ischemic or haemorrhagic stroke, were aged ≥18 years, had clinical dysphagia identified using bedside testing, were alert or rousable, had a PAS ≥3 for at least 1 swallow, and could be treated within 42 days of stroke onset. Exclusion criteria: a history of dysphagia, dysphagia from a condition other than stroke, advanced dementia, implanted pacemaker or cardiac defibrillator in situ, unstable cardiopulmonary status or a condition that compromised cardiac or respiratory status, distorted oropharyngeal anatomy, additional diagnosis of a progressive neurological disorder, receiving continuous oxygen treatment, or pregnant or nursing mother. |
Technique | PES with Phagenyx (Phagenesis, Ltd, Manchester, UK). Electric current at 5 Hz was administered for 10 minutes each day for 3 days. The current of the stimulation was calculated as the threshold current (the current at which the patient can first detect stimulation) plus 75% of the difference between threshold and tolerance current (the current at which the patient does not want the current increased further). The mean treatment stimulation level was 14.5 mA in those randomised to PES. |
Follow up | 12 weeks |
Conflict of interest/source of funding | Conflict of interest: The lead author received honoraria for work as the chief investigator and for consultancy. One author is the co-founder of Phagenesis, the manufacturer of a PES device. One author was an employee of Phagenesis. Source of funding: The trial was sponsored and funded by Phagenesis, the manufacturer of a PES device. |
Analysis
Follow up issues: Of 162 people who were randomised, treatment was attempted in 152 (safety population), 141 were treated (with at least 1 session of PES or sham), videofluoroscopy was obtained in 126 at 2 weeks (primary outcome population), and in 95 at 12 weeks.
Study design issues: This RCT assessed the efficacy and safety of PES to treat post-stroke dysphagia. Patients with recent stroke and confirmed dysphagia were randomised 1:1 to PES or sham. The sample size was based on statistical power calculations such that the trial had 90% power to detect a difference of 1.1 points on the PAS at a 2-sided significance level of 5%. Patients and outcome assessors were blinded to treatment allocation, treating researchers were unblinded. Patients randomised to sham therapy had no stimulation after establishment of threshold and tolerated levels of current. This determination of threshold and tolerated levels of current may have inadvertently exposed sham patients to therapeutic stimulation. As patients could feel the effects of treatment, or the absence of treatment with sham, some patients may have become prematurely unblinded to treatment allocation. The authors also reported that there was evidence of suboptimal treatment, with 58% of PES-treated patients had a treatment level less than 10.2 mA (a figure chosen from earlier research), identical treatment and threshold levels, or a treatment level less than threshold.
The outcomes included:
Primary: PAS at 2 weeks
Secondary: PAS at 12 weeks, DSRS, modified Rankin Scale, Barthel Index, NIHSS, HRQoL, and nutritional measures.
The primary outcome was analysed using multiple linear regression. Secondary outcomes were analysed using multiple linear regression (for continuous outcomes), ordinal logistic regression (ordered categorical data), binary logistic regression (dichotomous data), and Kaplan–Meier and Cox regression models (time to event). There was no adjustment for multiple comparisons reported.
Study population issues: No statistical analysis was performed, but the authors reported that the PES and sham groups were 'well balanced at baseline'. Some select baseline characteristics follow. Most people were white (85.8%), with smaller numbers of Asian (9.3%), black (2.5%), and 'other' (2.5%) people. Stroke types were ischaemic/normal (88.8%) and intracerebral haemorrhage (10.6%). The mean time from stroke to randomisation was 13 days.
Key efficacy findings
PAS
Number of people analysed: 126
There were no statistically significant differences in the change from baseline to 2 weeks in PAS scores between the PES and sham groups (mean difference=0.14; 95% CI -0.37 to 0.64; p=0.60).
There was also no statistically significant difference in the proportion of people who had any PAS >3 between the PES and sham groups (85.7% vs. 80.4%, p=0.79).
At 12 weeks, there was no statistically significant difference in the mean PAS scores between the PES and sham groups (mean difference=0.29; 95% CI −0.04 to 0.99; p=0.41).
There were no statistically significant interactions observed in subgroup analysis.
All (N=126) | PES (N=70) | Sham (N=56) | OR/MD (95% CI), Adjusted | p | OR/MD (95% CI), Unadjusted | p | |
Baseline | |||||||
PAS (/8) | 4.8 (2.0) | 4.8 (2.1) | 4.7 (1.9) | - | - | - | - |
2 week primary outcome | |||||||
Mean of all boli (/8) | 3.6 (2.0) | 3.7 (2.0) | 3.6 (1.9) | 0.14 (−0.37 to 0.64) | 0.60 | 0.06 (−0.62 to 0.74) | 0.86 |
Change from baseline | −1.2 (1.8) | −1.2 (1.8) | −1.2 (1.8) | 0.14 (−0.37 to 0.64) | 0.60 | 0.00 (−0.62 to 0.61) | 1.00 |
Any PAS >3 (%) | 105 (83.3) | 60 (85.7) | 45 (80.4) | 1.22 (0.29 to 5.15) | 0.79 | 1.47 (0.57 to 3.75) | 0.42 |
12 week | |||||||
Mean of all boli (/8) | 3.2 (2.1) | 3.3 (2.2) | 3.0 (2.1) | 0.29 (−0.04 to 0.99) | 0.41 | 0.24 (−0.6 to 1.08) | 0.57 |
Any PAS >3 (%) | 69 (72.6) | 36 (70.6) | 33 (75.0) | 0.62 (0.20 to 1.90) | 0.41 | 0.80 (0.32 to 1.99) | 0.63 |
Repeated measures | |||||||
Mean (/8)* | - | 4.1 (2.3) | 3.9 (2.3) | 0.51 (−0.23 to 1.25) | 0.18 | 0.19 (−0.67 to 1.04) | 0.67 |
All patients had diagnostic videofluoroscopy at both baseline and 2 weeks and received at least 1 treatment session. Data are number (%), median (interquartile range), or mean (SD), with comparisons using unadjusted and adjusted multiple linear, ordinal logistic, or binary logistic regression. CI, confidence interval; MD, mean difference; OR, odds ratio; PAS, penetration-aspiration score; PES, pharyngeal electric stimulation.
*Includes death: PAS=9.
Secondary outcomes
Number of people analysed: various, see table below.
There were no statistically significant differences between the PES and sham groups in any of the secondary outcomes assessed.
N | All | PES | Sham | OR/HR/MD (95% CI), Unadjusted | p | OR/HR/MD (95% CI), Unadjusted | p | |
2 week | ||||||||
DSRS (/12)* | 133 | 5.1 (3.8) | 5.2 (4.1) | 4.9 (3.6) | 0.31 (−0.56 to 1.18) | 0.49 | 0.23 (−1.07 to 1.54) | 0.72 |
NIHSS (/42)* | 134 | 9.6 (7.2) | 9.0 (7.4) | 10.2 (7.1) | −0.05 (−1.42 to 1.32) | 0.94 | −1.19 (−3.64 to 1.26) | 0.34 |
mRS (/6)* | 134 | 3.9 (1.1) | 3.7 (1.2) | 4.1 (1.0) | 0.53 (0.23 to 1.22) | 0.14 | 0.49 (0.26 to 0.92) | 0.028 |
BI (/100)* | 134 | 36.2 (34.9) | 41.3 (37.2) | 29.8 (31.0) | 1.57 (−3.60 to 6.73) | 0.55 | 11.45 (−0.22 to 23.13) | 0.055 |
Death (%) | 141 | 2 (1.4) | 1 (1.3) | 1 (1.6) | … | … | 0.81 (0.05 to 13.13) | 0.88 |
12 week | ||||||||
DSRS (/12)* | 124 | 4.2 (5.1) | 4.4 (5.2) | 3.9 (5.1) | 1.01 (−0.44 to 2.46) | 0.17 | 0.58 (−1.23 to 2.39) | 0.53 |
EQ-5D as HUS (/1)* | 113 | 0.02 (0.40) | 0.08 (0.41) | −0.04 (0.39) | 0.13 (0.00 to 0.27) | 0.054 | 0.12 (−0.03 to 0.27) | 0.11 |
EQ-VAS* | 105 | 50.3 (30.7) | 51.6 (30.1) | 48.6 (31.7) | −4.17 (−15.22 to 6.88) | 0.46 | 3.03 (−8.70 to 14.76) | 0.61 |
Disposition (%) | 141 | 0.66 (0.30 to 1.49) | 0.32 | 0.63 (0.31 to 1.26) | 0.19 | |||
Home | 30 (21.3) | 20 (25.6) | 10 (15.9) | … | … | … | … | |
Institution | 93 (66.0) | 49 (62.8) | 44 (69.8) | … | … | … | … | |
Died | 18 (12.8) | 9 (11.5) | 9 (14.3) | … | … | … | … | |
Time to event | ||||||||
Discharge (days) | 141 | 28.2 (22.8) | 27.7 (22.7) | 28.7 (23.0) | −0.33 (−7.79 to 7.12) | 0.93 | −0.97 (−9.72 to 7.78) | 0.83 |
Death (%) | 141 | 18 (12.8) | 9 (11.5) | 9 (14.3) | 1.11 (0.34 to 3.59) | 0.86 | 0.79 (0.32 to 2.00) | 0.62 |
BI, Barthel Index; DSRS, dysphagia severity rating scale; EQ-5D, European Quality of Life-5 Dimensions; EQ-VAS, European Quality of Life Visual Analogue Scale; HR, hazard ratio; HUS, health utility status; MD, mean difference; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; and PES, pharyngeal electric stimulation.
*Includes death: NIHSS=43, DSRS=13, mRS=6, BI=−5, and HUS=0.
Key safety findings
Number of people analysed: 152
There was no statistically significant difference in the rate of SAEs at the end of follow up: Total n=40 (26.3%), PES n=22 (25.9%), sham n=18 (26.9%; p=1.00).
No SADEs occurred in either group.
Any | Fatal | |||||||
All | PES | Sham | p | All | PES | Sham | p | |
Patients | 152 | 85 | 67 | 152 | 85 | 67 | ||
Cardiac | 9 (5.9) | 6 (7.1) | 3 (4.5) | 0.73 | 4 (2.6) | 2 (2.4) | 2 (3.0) | 1.00 |
Gastrointestinal | 2 (1.3) | 2 (2.4) | 0 (0) | 0.50 | 0 (0) | 0 (0) | 0 (0) | - |
General | 3 (2.0) | 0 (0) | 3 (4.5) | 0.083 | 3 (2.0) | 0 (0) | 3 (4.5) | 0.083 |
Hepatobiliary | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 | 0 (0) | 0 (0) | 0 (0) | - |
Infections | 11 (7.2) | 6 (7.1) | 5 (7.5) | 1.00 | 4 (2.6) | 2 (2.4) | 2 (3.0) | 1.00 |
Investigations | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 | 0 (0) | 0 (0) | 0 (0) | - |
Neoplasms | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 | 1 (0.7) | 1 (1.2) | 0 (0) | 1.00 |
Nervous system | 8 (5.3) | 4 (4.7) | 4 (6.0) | 0.73 | 4 (2.6) | 3 (3.5) | 1 (1.5) | 0.63 |
Renal/urinary | 2 (1.3) | 1 (1.2) | 1 (1.5) | 1.00 | 0 (0) | 0 (0) | 0 (0) | - |
Respiratory | 8 (5.3) | 5 (5.9) | 3 (4.5) | 1.00 | 2 (1.3) | 1 (1.2) | 1 (1.5) | 1.00 |
Surgical/medical | 2 (1.3) | 2 (2.4) | 0 (0) | 0.50 | 0 (0) | 0 (0) | 0 (0) | - |
Total SAEs | 40 (26.3) | 22 (25.9) | 18 (26.9) | 1.00 | 18 (11.8) | 9 (10.6) | 9 (13.4) | 0.62 |
Total SADEs | 0 (0) | 0 (0) | 0 (0) | - | 0 (0) | 0 (0) | 0 (0) | - |
PES, pharyngeal electrical stimulation; SADE, serious adverse device-related event; SAE, serious adverse event.
Study details
Study type | Multicentre, double-blinded (patients, assessors), sham-controlled RCT followed by open-label crossover period |
Country | Austria, Germany, Italy |
Recruitment period | 2015 to 2017 |
Study population and number | n=69 (35 active treatment) People with recent stroke and dysphagia who required tracheostomy. |
Age and sex | Mean 64 years; 64% male |
Patient selection criteria | Inclusion criteria: supratentorial stroke (haemorrhagic or ischaemic), mechanically ventilated for at least 48 hours post-stroke, successfully weaned from mechanical ventilation but remained tracheostomised, free of sedation for at least 3 days at the time of first decannulation screening, scored -1 or more points on the Richmond Agitation and Sedation Scale, and could not be decannulated due to severe dysphagia. Exclusion criteria: infratentorial stroke, pre-existing dysphagia, pre-existing disease that typically causes dysphagia (for example Parkinson's disease), participation in any other study potentially influencing the outcome of PES, presence of a cardiac pacemaker or an implantable defibrillator, nasal deformity or previous oesophageal surgery or any other circumstance where placement of a standard nasogastric tube would be deemed unsafe, need for high levels of oxygen supply (more than 2 l/min), required emergency treatment, or had less than 3 months life expectancy. |
Technique | PES with Phagenyx (Phagenesis, Ltd, Manchester, UK). Electric current at 5 Hz was administered for 10 minutes each day for 3 days. The current of the stimulation was calculated as the threshold current (the current at which the patient can first detect stimulation) plus 75% of the difference between threshold and tolerance current (the current at which the patient does not want the current increased further). The mean treatment stimulation level was 33.6 mA in those randomised to PES. |
Follow up | 90 days |
Conflict of interest/source of funding | Conflict of interest: One author is the co-founder of Phagenesis, the manufacturer of a PES device. Other authors report fees from Phagenesis for travel, training, and payments per-patient for the study conduct, amongst others. Source of funding: Funded by Phagenesis, the manufacturer of a PES device. |
Analysis
Follow up issues: Of 69 people randomised, 68 had day 2 data, 65 had day 30 or hospital discharge data, and 52 had day 90 data.
Study design issues: This RCT assessed the efficacy and safety of PES for early decannulation of people who had post-stroke dysphagia. Patients were randomised 1:1 to PES or sham and received 3 days of treatment. Readiness for decannulation was assessed 24 to 72 hours after the final stimulation. Those who remained cannulated could then enter an open-label phase. The maximum sample size was set at 140 people to detect an absolute difference between the groups of 25%, assuming that the control rate would be 20%, significance level of 0.05, and power 0.80. Predetermined interim analyses were performed when recruitment reached 50 patients, 70 patients, and every 10 patients after. At the 70-patient interim analysis, the study was stopped for superiority. Patients and outcome assessors were blinded to treatment allocation, treating researchers were unblinded. As patients could feel the effects of treatment, or the absence of treatment with sham, some patients may have become prematurely unblinded to treatment allocation.
The outcomes included:
Primary: readiness for decannulation 24 to 72 hours after 3 days of PES
The presence of massive pooling of saliva, limited spontaneous swallows (less than 1 per minute), and/or no sensation elicited by endoscope contact with the laryngeal vestibule meant that patients were not ready for decannulation.
Secondary: treatment effect in delayed and retreated patients, necessity of recannulations (at day 2 and during follow-up of 30 days or until discharge, whichever is first), dysphagia scores (DSRS, FOIS), severity of stroke (modified Rankin Scale and National Institutes of Health Stroke Scale scores; at day 2, during follow-up of 30 days or until discharge, whichever was first), length of stay on different levels of care, Speech and Language Therapy management plan, number and type of AEs, including adverse device-related events.
Outcomes were analysed using Fisher's exact test for binary data, Mann-Whitney-U test for ordinal data, and Student's t-test (pooled) for continuous data. Regressions were performed using binary logistic regression, Cox regression and multiple linear regression. p<0.05 was considered statistically significant. No adjustment was made for multiple comparisons, and all analyses were by intention to treat.
Study population issues: No statistically significant differences in baseline characteristics were reported between the treatment groups. Overall, 49 (71%) patients had an ischemic stroke, and 20 (29%) an intracerebral haemorrhage. The median time from stroke to randomisation was 28 days.
Key efficacy findings
Decannulation
Number of people analysed: 69
In the primary outcome, there was a higher likelihood of readiness for decannulation 24 to 72 hours after treatment with PES compared to sham, OR: 7.00 (95% CI 2.41 to 19.88, p=0.00082).
No patients who had decannulation performed required re-cannulation over the next 48 hours, or during their documented follow-up period up to hospital discharge.
Based on these outcome data, the study was stopped for superiority by an Independent Data and Safety Monitoring Board.
In predefined subgroups, statistically significant treatment-by-subgroup interactions were present, these favouring treatment in patients treated earlier after stroke, or with a shorter duration of mechanical ventilation.
Considering both the randomised and open-label parts of the study, a total of 57% of the patients became ready for decannulation 24 to 72 hours after PES.
Total | PES | Sham | OR (95% CI) | p | |
Randomised part 1 of the study | |||||
Patients | 69 | 35 | 34 | ||
Ready for decannulation after PES/Sham (%; Primary outcome) | 17 (49) | 3 (9) | 7.00 (2.41-19.88) | 0.00082 | |
Removal of the tracheal tube (%)* | 14 (82) | 1 (33) | 9.33 (0.62-139.57) | 0.1404 | |
Deflation of the tube-cuff (%)* | 3 (18) | 1 (33) | 0.43 (0.03-6.41) | 0.5088 | |
Open-label part 2 of the study | |||||
Patients | 45 | 15 | 30 | ||
Ready for decannulation" after open-label treatment** (%) | 20 (44) | 4 (27) | 16 (53) | 0.32 (0.08-1.23) | 0.1185 |
Removal of the tracheal tube (%)* | 17 (38) | 3 (20) | 14 (47) | 0.29 (0.07-1.22) | 0.1097 |
Deflation of the tube-cuff (%)* | 3 (7) | 1 (7) | 2 (7) | 1.00 (0.08-12.00) | 1.0000 |
Re-cannulation within 48 hrs (%) | 0 (0) | 0 (0) | - | - | |
Re-cannulation within 30 days or hospital discharge (whichever is first; %) | 0 (0) | 0 (0) | - | - |
OR, odds ratio; PES: pharyngeal electrical stimulation.
*Statistical comparison within the subgroup of patients reaching the primary endpoint.
**These are data related only to the open label part of the study where all non-responders were given PES.
One patient in the PES group had a non-treatment-related adverse event occurring prior to third day of PES which required transfer to another hospital for surgery; as a result, assessment was not possible. Conservatively, the patient was assigned to no decannulation.
Secondary outcomes
Number of people analysed: Various, see table below.
There were no differences between the groups in secondary outcomes.
Total | PES | Sham | OR/MD (95% CI) | p | |
DSRS, N, mean (SD) | |||||
Baseline | 12 (0) | 12 (0) | |||
Day 2 | 60 | 30, 10.6 (2.4) | 30, 10.4 (2.7) | 0.27 (-1.05, 1.59) | 0.6873 |
Day 30 or Hospital Discharge (whichever is first) | 50 | 25, 8.0 (4.6) | 25, 8.9 (3.3) | -0.88 (-3.17, 1.41) | 0.4437 |
Day 90 | 53 | 27, 4.6 (5.3) | 26, 5.7 (5.1) | -1.10 (-3.97, 1.77) | 0.4449 |
FOIS, N, mean (SD) | |||||
Baseline | 1 (0) | 1 (0) | |||
Day 2 | 61 | 31, 1.7 (1.2) | 30, 1.9 (1.4) | -0.191 (-0.878, 0.495) | 0.5789 |
Day 30 or Hospital Discharge (whichever is first) | 50 | 25, 3.0 (2.4) | 25, 2.5 (1.7) | 0.560 (-0.61, 1.73) | 0.3407 |
Day 90 | 53 | 27, 4.6 (2.6) | 26, 3.9 (2.5) | 0.745 (-0.660, 2.150) | 0.2922 |
NIHSS, N, mean (SD) | |||||
Baseline | 68 | 34, 17.6 (5.0) | 34, 17.5 (4.3) | 0.118 (-2.129, 2.364) | 0.9170 |
Day 2 | 47 | 24, 15.6 (4.5) | 23, 15.7 (6.4) | -0.027 (-3.287, 3.233) | 0.9867 |
Day 30 or Hospital Discharge (whichever is first) | 48 | 24, 14.0 (5.0) | 24, 13.8 (5.9) | 0.292 (-2.865, 3.448) | 0.8533 |
Day 90 | 16 | 8, 10.1 (9.2) | 8, 16.9 (8.6) | -6.750 (-16.281, 2.781) | 0.1510 |
mRS, N, mean (SD) | |||||
Baseline | 68 | 34, 5.0 (0.0) | 34, 5.0 (0.2) | 0.029 (-0.029, 0.088) | 0.3210 |
Day 2 | 61 | 31, 4.6 (1.3) | 30, 4.6 (1.3) | 0.078 (-0.570, 0.727) | 0.8094 |
Day 30 or Hospital Discharge (whichever is first) | 54 | 28, 4.8 (0.5) | 26, 4.7 (0.5) | 0.091 (-0.163, 0.345) | 0.4769 |
Day 90 | 51 | 26, 4.1 (0.8) | 25, 4.3 (1.0) | -0.203 (-0.730, 0.324) | 0.4421 |
Level of care | |||||
Baseline | |||||
Patients | 65 | 32 | 33 | ||
Intensive Care Unit | 8 (25) | 7 (21) | 1.24 (0.39-3.93) | 0.7746 | |
Intermediate Care Unit | 21 (66) | 23 (70) | 0.83 (0.29-2.35) | 0.7944 | |
Normal ward | 3 (10) | 3 (10) | 1.03 (0.19-5.55) | 1.0000 | |
Day 2 | |||||
Patients | 50 | 25 | 25 | ||
Intensive Care Unit | 3 (12) | 1 (4) | 3.27 (0.32-33.84) | 0.6092 | |
Intermediate Care Unit | 15 (60) | 16 (64) | 0.84 (0.27-2.65) | 1.0000 | |
Normal ward | 7 (28) | 8 (32) | 0.83 (0.25-2.78) | 1.0000 | |
Day 10 | |||||
Patients | 24 | 13 | 11 | ||
Intensive Care Unit | 2 (15) | 1 (9) | 1.82 (0.14-23.25) | 1.0000 | |
Intermediate Care Unit | 4 (31) | 5 (46) | 0.53 (0.10-2.84) | 0.6752 | |
Normal ward | 7 (54) | 5 (46) | 1.40 (0.28-7.02) | 1.0000 | |
Day 30 | |||||
Patients | 14 | 7 | 7 | ||
Intensive Care Unit | 0 (0) | 0 (0) | - | - | |
Intermediate Care Unit | 2 (29) | 1 (14) | 2.40 (0.16-34.93) | 1.0000 | |
Normal ward | 5 (71) | 6 (86) | 0.42 (0.03-6.06) | 1.0000 |
DSRS: dysphagia severity rating scale; FOIS: functional oral intake scale; NIHSS: National Institute of Health Stroke Scale; MD, mean difference; mRS: modified Rankin Scale; OR, odds ratio; PES: pharyngeal electrical stimulation.
Key safety findings
Number of people analysed: 69
A total of 7 people in the PES group (20%), 3 people in the sham group (9%) and 1 person prior to randomisation (8%) died during the study.
None of the deaths were judged to be PES-treatment or investigational device- (base station and catheter) related by the Independent Data and Safety Monitoring Board.
There was no statistically significant difference between the number of people with at least 1 SAE in the treatment groups.
A total of 12 non-serious device-related adverse events were observed in 8 different people.
Data are number of events (number of patients [%]) | PES | Sham | Non-randomised** |
SAEs: | |||
Prior randomisation* | 1 (1 [3%]) | 1 (1 [3%]) | 3 (2 [17%]) |
0-1 month after randomisation | 3 (3 [9%]) | 4 (4 [12%]) | |
1-3 months after randomisation | 8 (7 [20%]) | 4 (1 [3%]) | |
Total study | 12 (10 [29%]) | 9 (8 [24%]) | 3 (2 [17%]) |
Most commonly observed SAEs (3 or more events) | |||
Pneumonia | 2 (2 [6%]) | 1 (1 [3%]) | |
Cardiac Arrest | 2 (2 [6%]) | 1 (1 [3%]) | |
Sepsis | 3 (3 [9%]) | 4 (4 [12%]) | |
Hydrocephalus | 2 (2 [6%]) | 0 | 1 (1 [8%]) |
Death | 7 (7 [20%]) | 3 (3 [9%]) | 1 (1 [8%]) |
AEs (non-serious) | 55 (21 [60%]) | 50 (21 [62%]) | 0 |
Most commonly observed AEs (3 or more events) | |||
Diarrhoea | 2 (2 [6%]) | 4 (4 [12%]) | |
Vomiting | 6 (4 [11%]) | 6 (2 [6%]) | |
Pneumonia | 3 (3 [9%]) | 6 (5 [15%]) | |
Urinary Tract Infection | 8 (7 [20%]) | 3 (3 [9%]) | |
Infection (Other) | 6 (6 [17%]) | 4 (3 [9%]) | |
Musculoskeletal Pain | 3 (2 [6%]) | 0 | |
Hypoxia | 2 (2 [6%]) | 1 (1 [3%]) | |
Thrombophlebitis | 2 (2 [6%]) | 1 (1 [3%]) | |
Adverse Device-related Events (ADEs) | 8 (5 [14%]) | 4 (3 [9%]) | |
Most commonly observed ADEs (3 or more events) | |||
Medical Device Complication | 6 (5 [14%]) | 3 (2 [6%]) | |
Serious ADEs (SADEs) | 0 | 0 |
*Prior randomisation is defined as period from date of informed consent to date of randomisation.
**Non-randomised is defined as patients who were never ultimately randomised.
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