PDF: PHADER
(2020)Objective
To assess the real-world effect of pharyngeal electrical stimulation (PES) on dysphagia severity in patients with neurogenic dysphagia from stroke, traumatic brain injury, or other neurological conditions
Study Summary
• Stroke not ventilated: DSRS change -6.7 (95% CI -7.8, -5.5); stroke ventilated: -6.5 (-7.6, -5.5); ventilator-related: -6.6 (-8.4, -4.8); TBI: -4.5 (-6.6, -2.4)
• FOIS improved by 2.9 points and PAS improved by 4.1 units across all participants (both p<0.001)
• In ventilated patients who could be decannulated, DSRS improvement was -7.5 vs -2.1 in those who could not (p<0.001)
• Earlier treatment (<32 days from onset) associated with greater DSRS improvement: -7.7 vs -4.7 (p<0.001)
• PES was well tolerated; catheter insertion took mean 12 min with ease score >5/7
• 74 SAEs in 60 participants (9.2%); pneumonia most common (11%); only 1 SAE possibly related to catheter insertion
Intervention
Pharyngeal electrical stimulation (PES) via Phagenyx Base Station and catheter, 5 Hz for 10 min daily on 3 consecutive days, at 75% of tolerable limit above sensory threshold
Inclusion Criteria
Adults with oropharyngeal dysphagia (DSRS score ≥6) related to: (A) stroke not requiring ventilation, (B) stroke requiring ventilation and tracheotomy, (C) mechanical ventilation non-stroke/non-TBI, (D) TBI, or (E) other neurological cause. Key exclusions: non-neurogenic dysphagia, implanted cardiac pacemaker or cardioverter defibrillator, pregnancy
Study Design
Arms: Array
Patients per Arm: 245 total (single arm)
Outcome
• FOIS change: +2.9 (2.5, 3.3) from baseline 1.4 to 4.3 (p<0.001)
• PAS change: -4.1 units from 8.9 to 6.8 at day 92
• Decannulation achieved in ~2/3 of ventilated patients
• Post hoc adjusted OR for improved DSRS: 0.22 (95% CI 0.13, 0.38; p<0.001)
• Compared with STEPS sham group: PHADER non-ventilated stroke patients improved 2.3 points more at 3 months (p=0.008)
• 74 SAEs in 60 patients; pneumonia 11%, cardiac arrest 2%, respiratory failure 1.6%
Bottom Line
In this prospective single-arm observational cohort of 245 patients with neurogenic dysphagia, PES was safe and associated with significant improvement in DSRS (-6.3 points), FOIS (+2.9 points), and PAS (-4.1 units) at 3 months across all diagnostic groups. Effects were greatest in patients treated earlier (<32 days) and in those who could be decannulated. However, the absence of a control group limits causal inference.
Major Points
- PHADER was a prospective single-arm observational cohort study conducted at 14 secondary/tertiary care centers in Austria, Germany, and the UK from March 2015 to September 2018, enrolling 245 patients with neurogenic dysphagia (DSRS ≥6).
- The primary outcome, DSRS score at 3 months, improved significantly from a baseline mean of 11.4 to 5.1 (mean difference -6.3; 95% CI -7.0 to -5.6; p<0.001), exceeding the minimum clinically important difference of 1 point. Improvement was seen in all diagnostic groups.
- DSRS improvement was significant in stroke without ventilation (-6.7; 95% CI -7.8, -5.5), stroke with ventilation (-6.5; -7.6, -5.5), ventilator-related non-stroke (-6.6; -8.4, -4.8), and TBI (-4.5; -6.6, -2.4). The TBI group showed smaller improvement, possibly due to diffuse brain damage.
- Secondary outcomes confirmed primary findings: FOIS improved by 2.9 points (p<0.001) and instrumentally-assessed penetration/aspiration (PAS) improved by 4.1 units (baseline 6.7 to 3.2 at day 92) across all participants and diagnostic groups.
- In ventilated patients with tracheotomy, approximately two-thirds could be decannulated. Decannulated patients showed greater DSRS improvement (-7.5 vs -2.1; p<0.001) than those who could not be decannulated.
- Earlier treatment was associated with greater benefit: patients treated <32 days from onset had DSRS improvement of -7.7 vs -4.7 for those treated ≥32 days (interaction p<0.001). Shorter ventilation duration (<22 days) also predicted greater improvement (p=0.048).
- Compared with sham-treated non-ventilated stroke patients from the STEPS phase III trial, PHADER patients improved 2.3 points more in DSRS at 3 months (p=0.008), though PHADER patients had more severe dysphagia at baseline.
- 74 SAEs occurred in 60 participants (1.2 per participant with SAE), with 29 fatal. Pneumonia was the most common SAE (27 events, 11.0%). Only 1 SAE was possibly related to catheter insertion. Treatment was well tolerated with mean catheter insertion time of 12 min and ease score >5/7.
Study Design
- Study Type
- Prospective, single-arm, multicenter observational cohort study
- Randomization
- No
- Blinding
- None (open-label observational)
- Sample Size
- 245
- Follow-up
- 3 months
- Centers
- 14
- Countries
- Austria, Germany, United Kingdom
Primary Outcome
Definition: DSRS at 3 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| N/A (single-arm) | Improved from 11.4 (baseline) to 5.1 (day 92); mean difference -6.3 (95% CI -7.0 to -5.6) | - (-7.0 to -5.6) | <0.001 |
Limitations & Criticisms
- Single-arm observational study with no control group — cannot establish causal relationship between PES and outcomes.
- Manufacturer-funded (Phagenesis Ltd) raises potential for bias in study design and reporting.
- Post hoc comparison with STEPS sham patients has significant limitations due to different study populations and time periods.
- Heterogeneous patient population (4 diagnostic groups analyzed) makes interpretation of overall results difficult.
- High SAE burden (74 events in 60 participants; 29 fatal) though only 1 possibly PES-related; open-label design likely under-reports SAEs.
- TBI subgroup showed smaller improvement, suggesting variable efficacy across etiologies.
- Instrumental assessments (VFS/FEES for PAS) were not mandated, leaving substantial missing data for secondary endpoints.
Citation
EClinicalMedicine 2020;28:100608