STIMIT Activator 1 Pivotal Study

Study Overview
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Brief Summary
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The study is a prospective, multi-center, randomized, controlled study using adaptive design to assess the evidence of safety and performance of the STIMIT Activator 1 System in the treatment of patients who have been mechanically ventilated for up to 48 hours and are predicted to require additional minimum 48 hours of mechanical ventilation or longer (adding up to MV time approximately 96 hours or longer).

Detailed Description
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The objective of this clinical investigation is to evaluate the safety and efficacy of the STIMIT Activator 1 device in subjects on mechanical ventilation who are on invasive mechanical ventilation (MV) and thus are at risk of diaphragmatic dysfunction/atrophy. The study is a prospective, multi-center, randomized, controlled study using adaptive design to assess the evidence of safety and performance of the STIMIT Activator 1 System in the treatment of patients who have been mechanically ventilated for up to 48 hours and are predicted to require additional minimum 48 hours of mechanical ventilation or longer (adding up to MV time approximately 96 hours or longer). This pivotal study is expected to include 40 subjects enrolled and device interventions in up to 6 centers focusing on North American sites (main focus USA, > 50% of study enrollment from US site). An interim analysis will be conducted after 30 patients have been treated to reconfirm sample size (adaptive design). This clinical study is anticipated to commence in the US upon approval by FDA and local IRB/EC site approval, and Canada upon approval of competent authorities and Ethics Committees. Enrollment and 10-day follow-up duration for primary endpoint of the study is expected to last 6 months. Subjects will be followed for 10 days or until they are successfully extubated (weaned) from mechanical ventilation, expire, or withdraw consent.

Official Title
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STIMIT Activator 1 Pivotal Study

Conditions
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Diaphragm Issues

Intervention / Treatment
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* Device: Stimit Activator 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent in writing from patient or the legally authorized representative Are 21 years or older, and, Have been on invasive mechanical ventilation ≤ 48hours and are predicted to remain on MV for an additional 48 hours or longer* Prediction at time of enrollment Exclusion Criteria: Patients that are planned to be treated with continuous infusion of neuromuscular blocking agents beyond the 48h enrollment period. Medical condition known to affect the phrenic nerve or respiratory muscles (non-exclusive list of medical conditions that could affect the phrenic nerve) Any patients with ICP probe Pre-existing severe chronic pulmonary disease (COPD GOLD stage IV, severe pulmonary fibrosis) Patients with metallic device implants or body penetrating metallic devices in the upper body area within 30cm (12inches) from the coils; known anatomy or devices in the neck area (e.g., ECMO cannulas in the neck area, collars or cranial appliances) that would interfere with headset placement or stimulation Any non-removable electrical / electronic device (device internal or external) that may be prone to interaction with, or interference from the STIMIT Activator, such as pacemakers, implantable defibrillators, implanted medication pumps, bio-stimulators, deep brain stimulators, implanted nerve stimulator, deep brain stimulators or cochlear device implants BMI >40 Cardiogenic or septic shock with ongoing severe hemodynamic instability as defined according to American College of Chest Physicians (Bone et al. 1992) (Singer et al. 2016)) that cannot be stabilized within the 48 hours enrollment period Physician thinks that the patient will not tolerate initial installation of the STIMIT respiratory sensor. Anticipating withdrawal of life support and/or shift to palliation as the goal of care (refer to Annex 2) Known to be pregnant Participating in another clinical trial studying an experimental Intervention that could affect the study primary outcome. Patients whose ultrasonographic assessment of right-sided diaphragmatic thickness would be difficult (e.g. local subcutaneous emphysema surrounding the zone of apposition, large dressings in the zone of apposition that cannot be removed). Patients with any neck incision, bruising, or other skin condition that places the subject at risk for burns.

Ages Eligible for Study
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Minimum Age: 21 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
Interventional Model Description: The study is a prospective, multi-center, randomized, controlled study using adaptive design to assess the evidence of safety and performance of the STIMIT Activator 1 System
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stimulation Group<br>The intervention group will receive non-invasive stimulation of the phrenic nerve for activation of the diaphragm. | Device: Stimit Activator 1<br>* The Stimit Activator 1 System will be used to stimulate the phrenic nerve resulting in diaphragm activation.<br>|
| No Intervention: Control Group<br>The control group will not received intervention and will be treated with standard of care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preservation of Diaphragm Thickness | The intra-individual change in diaphragm thickness will be measured daily via ultrasound. | Up to 10 days or extubation, whichever occurs first. | 
| the rate of device or procedure related serious adverse events | Events will be collected for intervention group during the course of treatment. | Up to 10 days or extubation, whichever occurs first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preservation of Diaphragm Thickness | The intra-individual change in diaphragm thickness will be measured daily via ultrasound. | Up to Day 4. | 
| Time to Rapid Shallow Breathing Index (RSBI) < 105 | Time from intubation to RSBI<105 breaths/min/L in days will be compared between Intervention and control groups. | UP to Day 10 | 
| Maximum Inspiratory Pressure (MIP) at extubation | MIP at extubation will be compared between the intervention and control groups. | UP to Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Invasive Phrenic Nerve Stimulation