Randomized Study of the pdSTIM™ System (Phrenic Nerve to Diaphragm STIMulation) in Failure to Wean Mechanically Ventilated Patients

This prospective, multi-center, randomized, controlled clinical trial is being conducted to evaluate the safety and efficacy of the pdSTIM System to facilitate weaning from mechanical ventilation through phrenic nerve stimulation. Potential subjects who are on mechanical ventilation for at least four days and have failed at least one weaning attempt will be considered for the study. Those enrolled will be randomized in a 1:1 manner between the treatment group that is standard of care with the pdSTIM System and a Control group, which is standard of care alone.

The primary endpoints focus on time to weaning and serious adverse event rates between the Treatment and Control groups.

The pdSTIM Pivotal Study (ReInvigorate Study) is a prospective, multicenter, randomized, controlled clinical study to evaluate the safety and efficacy of the pdSTIM System to facilitate weaning from mechanical ventilation through phrenic nerve stimulation. Potential subjects who are on mechanical ventilation for ≥ 96 hours (4 days) and have failed at least one weaning attempt will be considered for the study.

Those enrolled will be randomized in a 1:1 manner between a Treatment group that is standard of care with the pdSTIM System and a Control group that is standard of care only. For the Treatment group, stimulation therapy with pdSTIM will occur daily until the subject is successfully removed from mechanical ventilation or the 30-Day follow-up visit, whichever is sooner. All randomized subjects will be followed to 60 (± 7) days post randomization. Total subject participation will be no longer than 67 days.

Eligibility Criteria:
Inclusion Criteria:

1. Subject is 18 years or older.
2. Subject, or subject's Legally Authorized Representative, understands study requirements, study visits, and is willing and able to provide written informed consent prior to study specific procedures or testing.
3. Subject has been on mechanical ventilation for ≥ 96 hours prior to randomization (intubation or tracheostomy).
4. Subject has failed at least 1 weaning attempt (e.g., site directed spontaneous breathing trial(s) did not result in liberation).
5. At the time of enrollment, the subject is likely to be ventilated for an additional 48 hours, at minimum, in the opinion of the investigator.

Exclusion Criteria:

1. Subject has been on invasive mechanical ventilation for \> 45 days.
2. Subject failed to wean due to pre-existing neurological or neuromuscular issues affecting the respiratory muscles (e.g., ALS, phrenic nerve paralysis, inflammatory muscle disease, underlying myopathy, myasthenia gravis, cervical spinal injury).
3. Subject's medical history, known anatomy or investigator's inability to visualize necessary anatomical landmarks that could prevent the safe placement of the pdSTIM leads.
4. Subject is at risk of significant hemorrhage or is currently receiving a full dose of systemic anticoagulation (e.g., IV heparin, high dose of subcutaneous heparin. Subjects on prophylactic anticoagulation or daily aspirin regimen on their own are not excluded unless other exclusion criteria apply).
5. Subject has an implant or external electrical device that may interact or interfere with the pdSTIM System (examples may include cardiac pacemaker, implantable defibrillator, vagal nerve stimulator, spinal cord stimulator, gastric stimulator, diaphragmatic stimulator).
6. Subject has been diagnosed and has been treated for neck cancer within the past 5 years or subject had any prior radiation treatment to the neck.
7. Subject currently has hemodynamic instability due to any cause (e.g., severe sepsis, hemorrhagic shock, or septic shock) with vasopressor support \> 0.1 mg/kg/min of norepinephrine or epinephrine, or equivalent, or is actively being titrated.
8. Subject has a local infection at or around the proposed pdSTIM Lead insertion site.
9. Subject is neutropenic or has signs of significant immunocompromise. (Subjects intubated for respiratory failure due to COVID-19 are not excluded unless other exclusion criteria apply).
10. Subject has severe COPD as indicated by evidence of significant expiratory obstruction on the ventilator flow waveform or, where ventilator flow waveforms are not utilized, has a FEV1 ≤ 30%.
11. Subject has pre-existing severe chronic pulmonary fibrosis.
12. Subject has pleural effusion occupying greater than 1/3 of the pleural space on either side.
13. Subject is currently on or expected to begin neuromuscular blockades.
14. Subject is anticipating withdrawal of life support and/or shift to palliation as the goal of care with less than 6-months life expectancy.
15. Subject is known or suspected to be pregnant or lactating.
16. Subject is currently enrolled in or exited early from a) any investigational drug study or b) an investigational device study that may impact the ability to wean or is directly related to the lungs or diaphragm.