Percutaneous Temporary Placement of a Phrenic Nerve Stimulator for Diaphragm Pacing

Study Overview
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Brief Summary
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A randomized clinical trial to investigate the use of the temporary Diaphragm Pacing Therapy System (DPTS) to rehabilitate the diaphragm in mechanically ventilated patients who have failed at least two weaning attempts. The goal is to strengthen and rehabilitate the diaphragm to liberate the patient more quickly from mechanical ventilation.

Detailed Description
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Mechanical ventilation (MV) is a life saving technology but can also cause damage to the lungs and diaphragm such as ventricular induced diaphragmatic dysfunction (VIDD). Research has shown that after being on mandatory MV and sedated the diaphragm begins to atrophy within as short as 18 hours. The Lungpacer Diaphragm Pacing Therapy System (DPTS) is a temporary therapy that consists of the Lungpacer IntraVenous Electrode Catheter (LIVE Catheter) and the Lungpacer Control Unit system. The LIVE Catheter is a proprietary central venous catheter that incorporates pacing electrodes in strategic areas that align with the left and right phrenic nerves. The LIVE Catheter can also be used for fluid delivery like any other central venous catheter. The randomized clinical trial will investigate the safety, effectiveness and performance of the Lungpacer DPTS. By stimulating the diaphragm through daily therapy sessions, with the intention of exercising and rehabilitating the diaphragm muscle so the patient may be able to be more quickly liberated from MV. The patient population includes those who have been mechanically ventilated for greater than or equal to 96 hours (4days), have failed two or more spontaneous breathing trials (SBT), and were not hypervolemic during the latest spontaneous breathing trial. Patients must have resolution of the initial indication for placement on mechanical ventilation before entering the trial.

Official Title
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Percutaneous Temporary Placement of a Phrenic Nerve Stimulator for Diaphragm Pacing

Conditions
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Ventilator Induced Diaphragm Dysfunction

Intervention / Treatment
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* Device: Diaphragmatic Pacing Therapy DPTS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older have been mechanically ventilated for > or = to 96 hours (4 days), and have satisfied the Readiness-to-Wean criteria and have failed at least two VLTs, one of which is the study specific VLT. Exclusion Criteria: currently on extracorporeal membrane oxygenation (ECMO); weaning failure due to hypervolemia; medical history or known anatomy that prevents insertion of the LIVE Catheter into the left subclavian vein; currently being treated with neuromuscular blockade; clinically overt congestive heart failure that is preventing weaning; pre-existing neuromuscular diseases 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 > or = 40; 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; prior bacteremia reported within the last 48 hours; current hemodynamic instability, sepsis or septic shock; terminally ill with 6 months or less life expectancy or not committed to full care; known or suspected to be pregnant or lactating; and 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Diaphragm Pacing Therapy DPTS<br>Diaphragm Pacing intervention will be conducted 2x a day using the Diaphragmatic Pacing Therapy System (DPTS). The DPTS includes the Lungpacer IntraVenous Electrode Catheter (LIVE Catheter) which is inserted temporarily into the left subclavian vein, the Lungpacer Control Unit (LCU external unit) and an intermediate cable that connects the LCU to the LIVE Catheter. | Device: Diaphragmatic Pacing Therapy DPTS<br>* Subjects will undergo DPTS 2 times a day until successfully extubated with no reintubation within 48 hours.<br>* Other names: LIVE Catheter;|
| No Intervention: Control Group<br>Standard of care treatment of weaning failure, no intervention is involved in this control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion successfully weaned by 30 days for subjects randomized to Treatment (Lungpacer DPTS) as compared to subjects randomized to Control. | Successfully weaned is defined as passing the protocol-specific Ventilator Liberation Trial (VLT), or removed from MV, and not reintubated (subjects with an oral or nasal, endotracheal tube) or returned to MV (subjects with a tracheostomy) within 48 hours | Patients will be allowed to stay in the study for up to 30 (+2 days of follow up for adverse events) days if not removed from mechanical ventilation sooner | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days on mechanical ventilation | Days on mechanical ventilation from randomization to removal from MV associated with successful weaning or Day 30, whichever comes first | from randomization to 30 days | 
| Changes in diaphragmatic thickening fraction on diaphragm ultrasound | Evaluate difference in changes in diaphragmatic thickening fraction between study allocation groups from randomization to successful weaning or on day 30 whichever comes first; | to successful weaning or on day 30 which ever comes first. | 
| Changes in MIP | Change in MIP from randomization to last available measure; Change in MIP over time from randomization (baseline). | to successful weaning, or on day 30, whichever comes first. | 
| Change in MIP | Rate of MIP change per day from randomization (baseline) to last available measure; | to successful weaning, or on day 30 whichever comes first. | 
| Changes in RSBI | Change in RSBI from randomization (baseline) to last available measure; Change in RSBI over time from randomization (baseline); | to successful weaning, or on day 30, whichever comes first | 
| Change in RSBI | Rate of RSBI change per day from randomization (baseline) to last available measure; | to successful weaning, or on day 30, whichever comes first | 
| Mortality | 30-day mortality | on day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diaphragm atrophy, VIDD, Weaning failure