PEPNS System Feasibility Study

Study Overview
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Brief Summary
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The purpose of this feasibility study is to evaluate the safety and performance of the PEPNS System in patients that need to be mechanically ventilated for at least 48 hours and up to 7 days in the Intensive Care Unit (ICU).

Detailed Description
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Mechanical ventilation is a life saving technology but can also cause damage to the lungs and diaphragm such as ventilator induced diaphragmatic dysfunction (VIDD). Research has shown that after being on mandatory mechanical ventilation and sedation the diaphragm begins to atrophy within as little as 18 hours. The PEPNS System consists of a console and disposable lead and will be used to stimulate the patient's diaphragm to contract in synchrony with the inspiratory cycle of the ventilator. The proprietary phrenic nerve to diaphragm stimulation (pdSTIM) Lead incorporates multipolar electrodes that align with the left and right phrenic nerves in order to stimulate the nerves to the diaphragm. This feasibility trial will investigate the safety and performance of the PEPNS System as a therapy by stimulating the diaphragm over a 48 hour period to facilitate weaning from the mechanical ventilator. The patient population includes those need to be mechanically ventilated for at least 48 hours and up to 7 days in the ICU.

Official Title
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Percutaneous Electrical Phrenic Nerve Stimulation (PEPNS) System Feasibility Study

Conditions
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Ventilator Induced Diaphragmatic Dysfunction (VIDD)

Intervention / Treatment
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* Device: PEPNS System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older (Adult). Able and willing to give informed consent or whose legally authorized representative is able and willing to give informed consent. Subject who in the opinion of the admitting consultant/intensivist is likely to be ventilated for > 48 hours from time of recruitment since study treatment will be for up to 48 hours. Exclusion Criteria: Subject has a left ventricular ejection fraction (LVEF) < 20%. Subject unlikely to survive 72 hours due to coexisting medical conditions. Subject has an implanted pulse generator or implanted electronic device: Subject has experienced an Acute Myocardial Infarction (AMI) within 72 hours prior to this screening or patient is on high dose inotropic support or subject is deemed to be in cardiogenic shock. Subject has significant bleeding diathesis, or is at risk of significant haemorrhage, patient is receiving full dose systemic anticoagulation Subject has a known or suspected phrenic nerve paralysis or neuromuscular or inflammatory muscle diseases where the diaphragm itself may not be functional. Subject has an active systemic infection or local infection at or around the insertion site. Subject is neutropenic or has signs of significant immunocompromise. Subject is known or suspected to be pregnant or is lactating. Subject will be unavailable for, or is unwilling to comply with, follow up requirements of the protocol. Subject is currently enrolled or is expected to be enrolled in any other study of an investigational drug or device who has received treatment under that protocol with the investigational product during the 30 days prior to screening. Subject has undergone a surgery or interventional procedure within the neck region aside from placement of an internal jugular (IJ) vein catheter. Subject has been diagnosed and has been treated for neck cancer within the past 5 years. Subject is known to have a demonstrated intra cardiac thrombus on echocardiography. Subject has uncontrolled hyperthyroidism, hypertension. Subject has had any cerebral ischemic event (Stroke or Transient Ischemic Attack TIA) in the 6-month interval preceding the screening date. Subject has degenerative nerve disorders such as amyotrophic laterals sclerosis (ALS). Subject has an elevated hemidiaphragm on chest x-ray. Subject written informed consent not obtained.

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
Intervention Model: Single Group Assignment
Interventional Model Description: The pdSTIM Leads are temporarily inserted near the right and left phrenic nerves and connected to the PEPNS System console. Duration of stimulation in PEPNS study is up to 48 hours to allow periodic electrical stimulation in daily sessions until the patients is weaned or 48 hours since initiation of stimulation session has elapsed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEPNS System<br>The pdSTIM lead will be temporarily inserted near the right and left phrenic nerves and connected to the PEPNS system console in order to stimulate the phrenic nerves and activate the diaphragm on the patients until extubated/removed from mechanical ventilation or until 48 hours has elapsed, whichever comes first. | Device: PEPNS System<br>* PEPNS System therapy will be delivered periodically up to 48 hours or less if patient is no longer being mechanically ventilated.<br>* Other names: pdSTIM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Capture of Left and/or Right Phrenic Nerve | Capture of the Left and/or Right Phrenic Nerve > 80% with an output parameter of < 10.5 volts. Capture was defined as diaphragmatic movement as a direct consequence of electrical phrenic nerve stimulation. Capture for this analysis was defined as synchrony of the stimulated breath with the output parameter <10.5 volts and Work of Breath between 0.2 and 2.0 Joules/L. Synchrony was achieved if the lag time between start of inspiration and start of stimulation was less than 88 ms. The proportion of successful capture was analyzed using a generalized linear mixed model accounting for subject and stimulation within subject as random effects, and the outcome of capture was yes/no based on whether the stimulation captures the diaphragm with multiple observations per subject. | Up to 48 hours | 
| Percent of Breaths Within Work of Breathing Range | Work of Breathing (WOB) kept between 0.2 and 2.0 joules/L for 80% of stimulated breaths. Outcome is measured as a percentage of stimulated breaths that had a WOB between 0.2 joules/L and 2 joules/L and the performance goal was 80%. | Up to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safe and Successful Lead Placement | The percentage of patients who receive safe and successful placement of the multipolar lead in the left and right phrenic nerve utilizing ultrasound guidance will be determined. | Up to 48 hours | 
| Phrenic Nerve Stimulation Effectiveness | Phrenic nerve stimulation in synchrony with Mechanical Ventilation breaths will be measured to verify that is occurs with inspiration. | Up to 48 hours | 
| Serious Device/Procedure Related Adverse Events | The percentage of patients who experience one or more serious device/procedure-related adverse events during the study will be reported. | Up to 48 hours |