Clinical trial NCT03840395: The PhINEST Study - Pharyngeal ICU Novel Electrical Stimulation Therapy
Official title: The PhINEST Study - Pharyngeal ICU Novel Electrical Stimulation Therapy: a Prospective, Multi-site, Randomised, Sham-controlled, Single-blind (outcome Assessor-blinded) Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dysphagia
Keywords: Dysphagia
Extubation
Intensive Care Unit
Pharyngeal Electrical Stimulation
Oropharyngeal Dysphagia
Mechanical Ventilation
Critically ill patients
Post-Extubation Dysphagia
Lead sponsor: Phagenesis Ltd.
Sponsor class: INDUSTRY
Collaborators: name: NAMSA
name: Cytel Inc.
First posted: 2019-02-15
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, multi-site, randomised, sham-controlled, single-blind (outcome assessor-blinded) study designed to assess the effects of Pharyngeal Electrical Stimulation (PES) (using Phagenyx®) for the treatment of oropharyngeal dysphagia after invasive mechanical ventilation (of any duration) by means of naso or oro-tracheal tube in critically ill intensive care unit (ICU) patients.

Detailed description: The PhINEST study is designed to assess the effects of Pharyngeal Electrical Stimulation (PES) (using Phagenyx®) for treatment of oropharyngeal dysphagia after invasive mechanical ventilation (of any duration) by means of naso or oro-tracheal tube in critically ill intensive care unit (ICU) patients.

The main clinical outcomes assessing unsafe swallows and dysphagia severity will be measured using the gold standard, i.e. Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and bedside swallowing assessments on day 2\* after completion of final PES treatment.

Randomisation will be on a 1:1 basis at each site stratified for neurological vs. non-neurological reason for admission (Acute Physiology and Chronic Health Evaluation (APACHE) IV diagnostic group). Patients will receive either PES/sham treatment in addition to standard supportive ICU care and standard of care treatments for dysphagia. Administration of all protocol-specific assessments will be conducted by personnel blinded to treatment assignment.

The study will follow an adaptive population enrichment and sample size re-estimation (SSR) design with one interim look. The study will start with a planned sample size of 200 patients and a maximum (evaluable) sample size of 360. Interim analysis after completion of approximately 140 (evaluable) patients will determine:

I. futility stopping; OR II. sample size increase for the overall sampled population; OR III. Enrichment based on the composite primary endpoint by pre-defined subgroups (neurological vs. non-neurological reason for admission according to APACHE IV diagnostic groups). Thus enrollment of patients in the non-performing sub-group will be stopped at the interim while a sample-size re-estimation based on conditional power will be carried out for the other sub-group.

All interim decisions will be based on conditional power which for the Finkelstein-Schoenfeld (FS)-statistic will need to be computed via Monte-Carlo simulations.

Up to thirty (30) investigational sites across Europe are planned to participate in this study which is expected to last 48 months from first patient first visit to last patient last visit. Patients will be assessed at the following intervals: screening, baseline, on day 2\* after completion of final study treatment, 7 ± 1 days after final study treatment and 14 ± 1 days after final study treatment (or hospital discharge if earlier). 30-day and 90-day mortality data will also be collected from the patients medical notes/electronic heath records/telephone call (no additional visit required).

\*The day two (FU1) visit is to be conducted on the second day (\~24hrs) following final PES treatment but may, under certain circumstances, be conducted upon/by the fourth day (\~60 hrs) following final study treatment in instances where the final study treatment is delivered on late Friday and where FEES assessment is only possible early on Monday as no weekend FEES service is available at the investigation site.

Eligibility criteria: Pre-screening Inclusion Criteria:

All of the following criteria must be met for inclusion:

* Age ≥ 18 ≤ 85,
* Emergency ICU admission (unplanned admission),
* Recent extubation following invasive mechanical ventilation (of any length of time) by means of endotracheal tube,
* Presence of post-extubation dysphagia as determined by the participating Sites' Standard Of Care (SOC).

Screening / Enrolment Criteria:

To be eligible for enrolment in this study, an individual must meet all of the following additional criteria:

* Presence of written informed consent according to respective national guidelines,
* Dysphagia severity status classified according to PAS on FEES assessment as 'aspiration' (PAS score ≥ 6),
* Richmond Agitation and Sedation Scale (RASS) score within the range of -1 to +2 (i.e. if score equals -2, -3, -4 or +3, +4, patient is excluded).

Randomisation Inclusion Criteria (post-consent)

The following additional criteria must be met for randomisation:

• Successful placement and subjective tolerance of the Phagenyx® Catheter within 2 days of extubation.(post consent)

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from enrolment in this study:

* Nasal anatomical deformity, nasal airway obstruction; patient who have had recent oral, nasal or oesophageal surgery or patient presenting with facial and/or cranial fractures or any other circumstance (e.g. history of oesophageal perforation, stricture, pouch, resection or rupture) where the placement of a standard nasogastric feeding tube (NGT) would be deemed unsafe,
* Cardiac or respiratory condition that might render the insertion (placement) of a catheter into the throat unsafe,
* Permanently implanted electrical devices,
* Are pregnant (pregnancy test) or known lactating women,
* Have non-neurogenic dysphagia (e.g. Cancer-related),
* Any prior tracheostomy,
* Patients who at the time of extubation have any treatment limitation (i.e., palliative care, life expectancy less than 48 hours, or are moribund), that prevents or would prevent compliance with study-specific instructions or procedures (as judged by the investigator),
* Severe cognitive impairment or other reasons that prevents compliance with study-specific instructions or procedures (as judged by the investigator),
* Previous history of dysphagia of any origin,
* Pre-existing tube feeding of any form (e.g. percutaneous gastric/enteral feeding tube related to previous injuries indicating previous dysphagia. NGTs are not an exclusion criterion),
* Participation in another interventional study (medicinal or device) that could influence the outcomes of PES,
* Treatment of dysphagia with other forms of electrical stimulation.

Primary outcomes:
measure: Effectiveness of Phagenyx® treatment in reducing severity of unsafe swallows - Penetration-Aspiration Scale (PAS) Scores
timeFrame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
measure: Effectiveness of Phagenyx® treatment in reducing the severity of unsafe swallows - Dysphagia Outcome and Severity Score (DOSS) score
timeFrame: 7±1 days after the final Phagenyx® treatment
Secondary outcomes:
measure: Effectiveness of Phagenyx® treatment in improving DOSS score.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on time from to feeding tube removal.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on time to oral intake.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on total days of enteral feeding.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment in improving Functional Oral Intake Scale (FOIS) score.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment in improving Dysphagia Severity Rating Scale (DSRS) score.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on time from extubation to ICU discharge
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on length of stay in ICU
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on length of stay in hospital.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on number of patients with re-intubation during hospital stay
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on mortality
timeFrame: Up to 90 days after completion of the final Phagenyx® treatment.
Other outcomes:
measure: Effectiveness of Phagenyx® treatment in reducing (dysphagia) secretion severity.
timeFrame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
measure: Effectiveness of Phagenyx® treatment in improving swallowing safety and efficiency - PAS scores
timeFrame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
measure: Effectiveness of Phagenyx® treatment in reducing bolus residue
timeFrame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
measure: Effectiveness of Phagenyx® treatment in reducing global dysphagia severity
timeFrame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
measure: Effectiveness of Phagenyx® treatment on time from extubation to hospital discharge
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on days on antimicrobials post-extubation (while in ICU)
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on hospital discharge destination
timeFrame: Up to 90 days after the final Phagenyx® treatment
measure: Effectiveness of Phagenyx® treatment on ICU readmission rate during hospital stay
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on tracheostomies per subgroup
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
measure: Effectiveness of Phagenyx® treatment on chest X-rays for suspected pneumonia.
timeFrame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck - Medizinische Universität Innsbruck
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck - Universitätsklinik für Anästhesie und Intensivmedizin
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck - Universitätsklinik für Innere Medizin I
city: Helsinki
country: Finland
facility: Helsinki University Hospital Perioperative, Intensive Care and Pain Medicine
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf - Klinik für Intensivmedizin
city: Bern
country: Switzerland
facility: University Clinic for Intensive Medicine, Inselspital
Study officials:
affiliation: University Clinic for Intensive Medicine, Inselspital, University of Bern
name: Joerg Schefold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medizinische Universität Innsbruck - Universitätsklinik für Innere Medizin I
name: Micheal Joannidis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medizinische Universität Innsbruck - Universitätsklinik für Anästhesie und Intensivmedizin
name: Christopher Rugg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medizinische Universität Innsbruck - Universitätsklinik für Neurologie
name: Alois Schiefecker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Hamburg-Eppendorf - Klinik für Intensivmedizin
name: Stefan Kluge, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schefold JC, Backlund M, Ala-Kokko T, Zuercher P, Mukherjee R, Mistry S, Mayer SA, Dziewas R, Bakker J, Jakob SM. The PhINEST study - Pharyngeal ICU Novel Electrical Stimulation Therapy: Study protocol of a prospective, multi-site, randomized, sham-controlled, single-blind (outcome assessor-blinded) study. Medicine (Baltimore). 2020 Mar;99(11):e19503. doi: 10.1097/MD.0000000000019503.