A Protocol Comparing Temporary Transvenous Diaphragm Pacing to Standard of Care for Weaning From Mechanical Ventilation

Study Overview
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Brief Summary
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This clinical investigation is an open-label, multi-center RCT to demonstrate the safety and effective performance of the Lungpacer DPTS (plus standard of care) as compared to Control (standard of care only) in patients aged 18 years or older who are receiving mechanical ventilation. Eligible Subjects will have received mechanical ventilation for ≥96 hours (4 days) and failed two weaning attempts. The goal or outcome is to show a numerically greater proportion of subjects weaned in the Treatment (Lungpacer DPTS) group as compared to the Control group.

Detailed Description
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The intended patient population is applicable for Lungpacer DPT because there are no noninvasive alternative treatments for patients who are difficult to wean from MV (i.e., ≥96 hours (4 days) on MV) or who have required prolonged MV (>7 days). The intended patient population includes approximately one-third of all patients on mechanical ventilation. Under standard of care, approximately 50% of these patients will recover from mechanical ventilation (Jung, 2016). Standard of care involves daily weaning attempts, known as Spontaneous Breathing Trials (SBTs) or Ventilator Liberation Trials (VLTs) that are intended to encourage diaphragm use and strengthening over time.Therefore, Lungpacer DPT efficacy evaluation must be compared to standard of care in a Control group. Lack of recovery from mechanical ventilation may be due to the inability of a patient to participate in VLTs or weaning attempts, due to extensive diaphragm weakness or sedation, the inability of VLTs to induce sufficient diaphragm strengthening, or co-morbidities that prevent recovery.

Official Title
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A Randomized, Controlled, Open-labeled, Multi-center Clinical Trial to Evaluate the Safe and Effective Performance of the Lungpacer Diaphragm Pacing Therapy System in Patients Who Have Failed to Wean From Mechanical Ventilation.

Conditions
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Ventilator Induced Diaphragm Dysfunction

Intervention / Treatment
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* Device: Lungpacer Diaphragm Pacing Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are 18 years or older, and, Have been mechanically ventilated for ≥96 hours (4 days), and, Have satisfied the Readiness-to-Wean criteria, and, Have failed at least 2 weaning attempts (that were conducted at least 48 hours after initiation of MV, and, that were conducted on different calendar days, and, at least one of which was the protocol-specific Ventilator Liberation Trial). Exclusion Criteria: MIP (absolute value) >50 cm H2O; Invasive mechanical ventilation >90 days; Currently on ECMO; Weaning failure due to hypervolemia; Medical history (including imaging) or known anatomy that prevents percutaneous insertion of the Catheter into the intended thoracic vein on the left side. Clinically overt congestive heart failure that is preventing weaning; Currently being treated with neuromuscular blockade; Pre-existing neurological, neuromuscular or muscular disorder that could affect the respiratory muscles; Pre-existing severe chronic pulmonary fibrosis; Pleural effusions occupying greater than one third of the pleural space on either side; BMI >45 kg/m2; Known or suspected phrenic nerve paralysis; Any electrical device (implanted or external) that may be prone to interaction with, or interference from the Lungpacer DPTS including neurological pacing/stimulator devices, cardiac pacemakers and defibrillators; Current hemodynamic instability, sepsis or septic shock; Prior bacteremia reported within the last 48 hours; Anticipating withdrawal of life support and/or shift to palliation as the goal of care; Known or suspected to be pregnant or lactating; Currently being treated in another clinical trial studying an experimental treatment that could affect the study primary outcome.

Ages Eligible for Study
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Minimum Age: 18 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: 1:1 randomization of treatment and control group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>Subject receives Lungpacer Catheter for transvenous phrenic nerve stimulation to deliver Diaphragm Pacing Therapy Sessions. DPT sessions are 6 sets of 10, delivered twice daily, for a total of 120 stimulation reps per day, plus standard of care for weaning from mechanical ventilation. | Device: Lungpacer Diaphragm Pacing Therapy<br>* Transvenous phrenic nerve stimulation to induce diaphragm contraction.<br>* Other names: AeroPace System;|
| No Intervention: Control<br>Subject does not receive Lungpacer Catheter or DPT. Subject receives only Standard of care for weaning from mechanical ventilation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful wean | The proportion of subjects who are successfully weaned will be statistically significantly greater for subjects randomized to Treatment (Lungpacer DPTS) compared to subjects randomized to Control. | 30 days | 
| Maximal Inspiratory Pressure mean change | The MIP mean change from baseline will be statistically significantly greater for subjects randomized to Lungpacer DPTS compared to subjects randomized to Control. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Rapid Shallow Breathing Index (RSBI) | Change in RSBI over time from randomization (baseline) | 30 days | 
| Mortality | To compare Treatment (Lungpacer DPTS) subjects to Control subjects for Day 30 mortality. | 30 days | 
| Rate of RSBI Change | Rate of RSBI change per day from randomization (baseline) to last available measure | 30 days | 
| Rate of MIP Change | Rate of MIP change per day from randomization (baseline) to last available measure; | 30 days | 
| Change in MIP | Change in MIP over time from randomization (baseline) | 30 days | 
| Days on MV | Days on mechanical ventilation from Day 1 to removal from MV associated with successful weaning or Day 30, whichever comes first. | Successful weaning or day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBT, VIDD, Diaphragm Atrophy, Weaning Failure, VILI, Phrenic Nerve Stimulation, Maximal Inspiratory Pressure, VLT