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

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.

Study Overview

• Status: Recruiting
• Conditions: Ventilator Induced Diaphragm Dysfunction
• Intervention / Treatment: Device: pdSTIM System Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Head of Clinical; Phone Number: 612-445-8252; Email: clinical@stimdia.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Chandler Regional Medical Center
    • Goodyear, Arizona, United States, 85395
      • Recruiting
      • Abrazo West Health
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Recruiting
      • Northeast Georgia Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • Tulane University Medical Center
    • Shreveport, Louisiana, United States, 71103
      • Recruiting
      • LSU Health Sciences Center at Shreveport
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Recruiting
      • Bryan Medical Center
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • University at Buffalo
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Atrium Health
    • Raleigh, North Carolina, United States, 27610
      • Recruiting
      • WakeMed Health
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Forsyth Medical Center
  • Texas
    • Georgetown, Texas, United States, 78626
      • Recruiting
      • St. David's Healthcare
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject is 22 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 (i.e., 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 Maximal Inspiratory Pressure (absolute value) > 50 cmH2O.
2. Subject has been on invasive mechanical ventilation for > 45 days.
3. 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).
4. 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.
5. 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).
6. 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).
7. 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.
8. 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.
9. Subject has a local infection at or around the proposed pdSTIM Lead insertion site.
10. 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).
11. Subject has severe COPD with evidence of significant expiratory obstruction on the ventilator flow waveform.
12. Subject has pre-existing severe chronic pulmonary fibrosis.
13. Subject has pleural effusion occupying greater than 1/3 of the pleural space on either side.
14. Subject is currently on or expected to begin neuromuscular blockades.
15. Subject has a severe head injury defined as having a Glasgow Coma Scale (GCS) score of 8 or less.
16. Subject has a do-not-reintubate order.
17. Subject is anticipating withdrawal of life support and/or shift to palliation as the goal of care with less than 6-months life expectancy.
18. Subject is known or suspected to be pregnant or lactating.
19. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care
Experimental: pdSTIM System Therapy	Device: pdSTIM System Therapy; Stimulate the phrenic nerves in synchrony with inspiratory cycles of the ventilator which exercises the diaphragm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Wean	Assess time to successful weaning from mechanical ventilation for the subjects randomized to Treatment as compared to subjects randomized to Control	Following completion of the 30-day follow-up by all available randomized subjects
Assessment of Serious Adverse Events (SAEs)	Assessment of Serious Adverse Events (SAEs) for the subjects randomized to Treatment as compared to subjects randomized to Control	Following completion of the 30-day follow-up by all available randomized subjects

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Maximal Inspiratory Pressure (MIP)	Assess mean change in maximal inspiratory pressure from baseline through Day 30 or at the time of successful weaning (whichever is first) for the subjects randomized to Treatment compared to subjects randomized to Control	Following completion of the 30-day follow-up by all available randomized subjects
Mortality Rates	Compare 30-day mortality rates of Treatment and Control subjects	Following completion of the 30-day follow-up by all available randomized subjects
Adverse Event Rates	Compare adverse event rates for Treatment and Control subjects	Following completion of the 30-day follow-up by all available randomized subjects
Days on Mechanical Ventilation	Compare number of days on mechanical ventilation from the date of randomization to removal of mechanical ventilation associated with successful weaning or Day 30, whichever comes first, for Treatment and Control subjects	Following completion of the 30-day follow-up by all available randomized subjects

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pdSTIM System Summary	Summarize pdSTIM System characteristics, such as lead placement success rate, duration of procedure, waveforms of flow/pressure, and pdSTIM System related complications	Following completion of the 30-day follow-up by all available randomized subjects
Mean Change in Rapid Shallow Breathing Index (RSBI)	Compare the mean change in Rapid Shallow Breathing Index from randomization to Day 30 or removal of mechanical ventilation, whichever comes first, for Treatment and Control subjects	Following completion of the 30-day follow-up by all available randomized subjects
Number of ICU Days	Compare the number of ICU days from randomization to Day 30 or removal of mechanical ventilation, whichever comes first, for Treatment and Control subjects	Following completion of the 30-day follow-up by all available randomized subjects
Rate of Re-intubation	Compare the rate of re-intubation following successful weaning for Treatment and Control subjects	Following completion of the 30-day follow-up by all available randomized subjects

Collaborators and Investigators

• Sponsor: Stimdia Medical Inc.
• Investigators: Principal Investigator: Steven Conrad, MD,PhD, LSU Health Sciences Shreveport

Publications and helpful links

Helpful Links

• Company Website

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: August 11, 2023
• First Submitted That Met QC Criteria: August 11, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Mechanical Ventilation; Phrenic Nerve Stimulation
• Other Study ID Numbers: CIP0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes