Pivotal Evaluation of Abdominal Neuromuscular Electrical Stimulation (VentFree) for Weaning From Mechanical Ventilation

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy of the VentFree Respiratory Muscle Stimulator (VentFree) in critically ill adult patients who require invasive mechanical ventilation, when compared to sham.

Detailed Description
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Approximately 40% of patients who receive invasive ventilation require more than four days of ventilator support. Every additional day of mechanical ventilation results in increased patient morbidity and mortality and increased economic cost. Mechanically ventilated patients often develop expiratory muscle weakness, which has been linked to failed extubation and weaning. Neuromuscular electrical stimulation (NMES) uses electrical pulses to induce a muscle contraction and has been shown to reduce or retard muscle atrophy. NMES applied to the abdominal wall muscles has been shown to improve respiratory function and assist ventilator weaning in spinal cord injury. Liberate Medical has previously shown that NMES applied to the abdominal wall muscles in synchrony with exhalation is feasible in patients receiving invasive mechanical ventilation. This study is a pivotal evaluation of the efficacy of exhalation synchronized abdominal NMES to assist ventilator weaning in critically ill patients.

Official Title
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A Randomized, Sham Controlled, Double-blinded, Multi-center Trial to Evaluate the Efficacy of the VentFree Respiratory Muscle Stimulator to Assist Ventilator Weaning in Critically Ill Patients

Conditions
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Respiration, Artificial, Ventilators, Mechanical

Intervention / Treatment
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* Device: Breath synchronized abdominal NMES
* Device: Sham breath synchronized abdominal NMES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is ≥ 22 years of age. Participant has been receiving invasive mechanical ventilation for ≥ 24 hours but ≤ 72 hours prior to enrollment. Participant or legally authorized representative is willing and able to provide written informed consent. Exclusion Criteria: Participant is scheduled or expected to be disconnected from mechanical ventilation ≤ 24 hours after enrollment. Participant has a BMI ≥ 40. Participant has no contraction of the abdominal wall muscles in response to abdominal FES as determined by ultrasound. Participant has a pre-existing neuromuscular or muscular disorder that could affect the respiratory muscles (e.g., spinal cord injury or Guillain-Barré syndrome). Participant has had open abdominal surgery ≤ 4 weeks prior to enrollment. Participant has open or damaged skin at area of electrode placements. Participant has a pacemaker and/or implanted electronic device. Participant has expected or diagnosed epilepsy. Participant is being treated for anaphylaxis. Participant is known or expected to be pregnant. NOTE: A negative urine or blood pregnancy test will be documented during screening for women of child-bearing potential. Participant is actively pharmacologically paralyzed at the time of enrollment. NOTE: Subjects receiving neuromuscular blockers may be enrolled after a ≥ 12 hour washout period. Participant is ventilated as a result of an uncomplicated elective surgery. The primary reason for ICU admission is an alcohol or drug overdose without secondary complication. Participant is tracheostomized at the time of enrollment. Participant is on home non-invasive ventilation (except for CPAP for obstructive sleep apnea). Participant has a life expectancy < 6 months based on medical history. Participant is participating in any of the following: A study with the same or similar primary endpoint A study investigating electrical stimulation or respiratory muscle therapy Any study in which the investigator determines may interfere with the results of this study Participant is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits. Participant has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VentFree Respiratory Muscle Stimulator<br>In the VentFree treatment group, abdominal functional electrical stimulation (FES) will be applied with a frequency of 30 hertz (Hz) and a pulse width of 350µs to cause a strong visible or palpable muscle contraction. The stimulation amplitude will be set to 90% of the participant's maximum tolerable level that does not cause discomfort to the participant. Participant discomfort will be measured using a visual analog pain scale (VAS) with pain ratings from zero (no pain) to ten (worst pain). For participants who are unable to communicate their level of pain, the Behavioral Pain Scale (BPS) will be used. The stimulation will be titrated for each participant and each stimulation session. After the stimulation has been titrated, a visible or palpable contraction of the abdominal wall will be confirmed. The stimulation will be evaluated every 10(± 2) minutes after the start of each stimulation session and adjusted as necessary so that no discomfort is caused to the participant. | Device: Breath synchronized abdominal NMES<br>* Active abdominal stimulation will be applied for 30 minutes twice per day (minimum of four hours between stimulation sessions), five days per week, for 28 days or ICU discharge, whichever comes first.<br>* Other names: VentFree Respiratory Muscle Stimulator;|
| Sham Comparator: Sham Respiratory Muscle Stimulator<br>In the sham group, abdominal functional electrical stimulation (FES) will be set to cause sensory stimulation but no muscle contraction. Abdominal FES will be applied with a frequency of 30 hertz (Hz), a pulse width of 350 µs and a stimulation amplitude that does not cause abdominal wall muscle contraction. The stimulation amplitude will initially be set at 10 mA and reduced in steps of 2 milliamp (mA) until no muscle contraction is seen. | Device: Sham breath synchronized abdominal NMES<br>* Sham abdominal stimulation will be applied for 30 minutes twice per day (minimum of four hours between stimulation sessions), five days per week, for 28 days or ICU discharge, whichever comes first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from first FES treatment administration to successful liberation during the treatment period of 28 days or until ICU discharge, whichever occurs first. | Successful liberation is defined as disconnection from mechanical ventilation that does not require invasive mechanical ventilation in the subsequent 7 days after disconnection, or until ICU discharge, or until live hospital discharge, whichever occurs first. | From first FES treatment to 28 days or ICU discharge, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough peak flow | Cough peak flow measurement | At 24 hours post-extubation | 
| Maximum expiratory pressure | Maximum expiratory pressure measurement | At 24 hours post-extubation | 
| Incidence of device-related adverse events | Number of device-related adverse events | From date of first FES treatment administration to date of hospital discharge or 90 days after treatment, whichever occurs first | 
| Time from first FES treatment administration to ICU discharge | Duration of first FES treatment administration to ICU discharge | From date of first FES treatment administration to date of ICU discharge or 90 days after treatment, whichever occurs first | 
| Time from first FES treatment administration to hospital discharge | Duration of first FES treatment administration to hospital discharge | From date of first FES treatment administration to date of hospital discharge or 90 days after treatment, whichever occurs first | 
| Incidence of patients who were successfully liberated from mechanical ventilation | Number of of patients who were successfully liberated from mechanical ventilation | From date of first FES treatment administration to date of hospital discharge or 90 days after treatment, whichever occurs first | 
| Incidence of re-intubations | Number of re-intubations | From date of first FES treatment administration to 90 days after treatment | 
| Incidence of readmissions to the ICU | Number of readmissions to the ICU | From date of first FES treatment administration to 90 days after treatment | 
| Incidence of readmissions to the hospital | Number of readmissions to the hospital | From date of first FES treatment administration to 90 days after treatment | 
| Incidence of acute respiratory infections | Number of participants that had diagnosed acute respiratory infections | From date of first FES treatment administration to date of hospital discharge or 90 days after treatment, whichever occurs first | 
| Incidence of hospital acquired infections | Number of participants that had diagnosed hospital acquired infections | From date of first FES treatment administration to date of hospital discharge or 90 days after treatment, whichever occurs first | 
| Incidence of tracheostomy | Number of participants that underwent tracheostomies | From date of first FES treatment administration to date of ICU discharge or 90 days after treatment, whichever occurs first | 
| Mortality | Number of Deaths | From Date of first FES treatment administration to date of hospital discharge or 90 days after treatment, whichever occurs first | 
| Maximum inspiratory pressure | Maximum inspiratory pressure measurement | At 24 hours post-extubation | 
| Mobility as assessed by the ICU Mobility Scale | Mobility assessment score from 0 (participant is unable to move) - 10 (participant is able to walk independently) | Date of ICU discharge or 90 days after treatment, whichever occurs first | 
| Quality of life as assessed by EQ-5D (Quality of Life Survey) | Five (5) level Quality of Life assessment ranging from Level 1 (indicating no problem) to Level 5 (indicating unable to/extreme problems) | At 90 days after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Muscle Stimulation, Mechanical Ventilation