pdSTIM System Therapy for Difficulty Weaning from Mechanical Ventilation

(ReInvigorate Trial)

Recruiting at19 trial locations

Overseen by Steven Conrad, MD,PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stimdia Medical Inc.

Must not be taking: Anticoagulants, Neuromuscular blockades

Disqualifiers: Neurological issues, Hemodynamic instability, COPD, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a device called the pdSTIM System that helps patients who have been on a ventilator for several days and couldn't stop using it. The device stimulates a nerve to strengthen breathing muscles, making it easier for patients to breathe without the ventilator. Using electrical stimulation to help breathing muscles has been explored as an alternative method to mechanical ventilation for patients with breathing difficulties.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on full-dose systemic anticoagulation (blood thinners) or have an implantable device that might interfere with the pdSTIM System, you may not be eligible to participate.

What data supports the effectiveness of the pdSTIM System Therapy for difficulty weaning from mechanical ventilation?

Research shows that stimulating the phrenic nerve, which controls the diaphragm, can help protect against diaphragm weakness caused by long-term use of a ventilator. This approach has been shown to help patients breathe better and wean off mechanical ventilation more easily. ^{1 2 3 4 5}

Is phrenic nerve stimulation safe for humans?

Phrenic nerve stimulation has been used since the 1980s for conditions like high spinal cord injuries and central hypoventilation, and it is generally considered safe. However, there can be rare complications, such as unintended stimulation of the phrenic nerve by pacemakers, which can be resolved. ^{6 7 8 9 10}

How is pdSTIM System Therapy different from other treatments for difficulty weaning from mechanical ventilation?

The pdSTIM System Therapy is unique because it involves stimulating the phrenic nerve, which directly controls the diaphragm, to help patients breathe more effectively. This approach is different from other treatments that may not target the nerve-diaphragm connection directly. ^{11 12 13 14 15}

Research Team

Steven Conrad, MD,PhD

Principal Investigator

LSU Health Sciences Shreveport

Eligibility Criteria

This trial is for adults aged 22 or older who have been on mechanical ventilation for at least four days and failed one weaning attempt. They should be expected to need ventilation for at least another two days. Pregnant women, those with certain medical devices, severe lung conditions, recent neck cancer treatments, or significant bleeding risks are excluded.

Inclusion Criteria

I have been on a breathing machine for at least 96 hours.

I am expected to need a ventilator for at least 48 more hours.

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

Exclusion Criteria

I have been on a breathing machine for more than 45 days.

I have severe long-term lung scarring.

I have a weakened immune system or low white blood cell count.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive daily stimulation therapy with the pdSTIM System until successful weaning from mechanical ventilation or the 30-day follow-up visit

Up to 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Extended Follow-up

Participants are followed to assess long-term outcomes and adverse events

Up to 67 days total participation

Treatment Details

Interventions

• pdSTIM System Therapy (Procedure)

Trial Overview The study tests the pdSTIM System's ability to help patients stop needing a ventilator by stimulating the phrenic nerve. Participants will either receive standard care alone (Control group) or standard care plus the pdSTIM System therapy (Treatment group), assigned randomly in equal numbers.

Participant Groups

Group I: pdSTIM System Therapy Experimental Treatment 1 Intervention

Group II: Standard of Care Active Control 1 Intervention

Who Is Running the Clinical Trial?

Stimdia Medical Inc.

Lead Sponsor

Trials

2

Recruited

430+

Findings from Research

Phrenic nerve stimulation (PNS) significantly protects against diaphragm dysfunction caused by mechanical ventilation (MV) in a study involving 21 rats, restoring diaphragm function and counteracting negative gene expression changes.

While mechanical ventilation led to impaired diaphragm contractility and reduced levels of insulin-like growth factor-1 (IGF-1), PNS was able to reverse these effects, suggesting a potential therapeutic role for PNS in patients requiring mechanical ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats. Yang, M., Wang, H., Han, G., et al.[2016]

The study demonstrates the feasibility of using transgastric endoscopic techniques to map the diaphragm and implant electrodes for stimulating diaphragm contractions, which could help wean ICU patients off mechanical ventilation.

In a porcine model, researchers successfully identified the diaphragm's motor point and implanted an electrode that allowed for diaphragm pacing, suggesting a potential new method for improving respiratory function in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diaphragm pacing with natural orifice transluminal endoscopic surgery: potential for difficult-to-wean intensive care unit patients. Onders, R., McGee, MF., Marks, J., et al.[2018]

The cervical approach for placing a phrenic nerve stimulator is a safe and effective method for improving breathing in patients with respiratory failure due to brainstem or spinal cord injuries.

Successful placement of the device was achieved without complications, highlighting the importance of understanding surgical anatomy and variations for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phrenic Nerve Stimulator Placement via the Cervical Approach: Technique and Anatomic Considerations. Padmanaban, V., Payne, R., Corbani, K., et al.[2021]

A new minimally invasive method for repositioning coronary sinus electrodes in patients with phrenic nerve stimulation (PNS) after cardiac resynchronization therapy was found to be safe and effective, with no pericardial effusion detected post-operation.

In a study of nine patients, the procedure successfully eliminated PNS in most cases, with stable pacing parameters maintained during a follow-up period of about 7.7 months, indicating a reduced burden on patients compared to traditional repositioning methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal invasive coronary sinus lead reposition technique for the treatment of phrenic nerve stimulation. Szilágyi, S., Merkely, B., Zima, E., et al.[2014]

The study demonstrated that using a transvenous phrenic nerve stimulating catheter is a feasible and safe method to stimulate the diaphragm in patients on prolonged mechanical ventilation, with successful catheter insertion in 9 out of 11 patients.

Of the patients who received the stimulation therapy, 7 out of 9 were successfully weaned from mechanical ventilation, showing significant improvements in respiratory function, including a 105% increase in maximal inspiratory pressure and a 44% improvement in the rapid shallow breathing index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary Transvenous Diaphragmatic Neurostimulation in Prolonged Mechanically Ventilated Patients: A Feasibility Trial (RESCUE 1). Ataya, A., Silverman, EP., Bagchi, A., et al.[2022]

Phrenic nerve stimulation appears to be a safe and effective method for reducing ventilator dependence in patients with high spinal cord injuries and central hypoventilation, based on a systematic review of 18 class IV studies.

Despite its potential benefits, the overall quality of the evidence is very poor, indicating a need for higher-quality research to better understand the efficacy and safety of this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation? Sieg, EP., Payne, RA., Hazard, S., et al.[2018]

In a study involving five patients with chronic central hypoventilation, diaphragm pacing using a spinal cord stimulator effectively provided stable ventilation for a follow-up period averaging 23 months without complications.

This method, which involves stimulating the phrenic nerve, shows promise as a feasible alternative treatment for central hypoventilation syndrome, especially in regions where traditional devices are unavailable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diaphragm pacing with a spinal cord stimulator]. Mitsuyama, T., Taira, T., Oikawa, A., et al.[2006]

In a study involving 4 patients with chronic hypoventilation due to brainstem dysfunction, diaphragm pacing using a spinal cord stimulator showed stable and sufficient ventilation over a follow-up period of 6 to 19 months, with no complications reported.

The method allowed one patient to become free from a respirator at night and enabled three respirator-dependent patients to become ambulatory during the day, indicating significant improvements in their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation for diaphragm pacing with a spinal cord stimulator: technical note. Taira, T., Takeda, N., Itoh, K., et al.[2019]

A diaphragm pacing system was successfully implanted in a 47-year-old man with respiratory insufficiency due to a brain stem tumor, allowing him to achieve almost normal respiration without mechanical ventilation.

After the implantation, the patient was weaned off mechanical ventilation within three weeks and transferred to a rehabilitation center, highlighting the efficacy of diaphragm pacing in restoring respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Implantation of a phrenic stimulator in central respiratory paralysis]. Fritz, U., Braun, U., Friedrich, M., et al.[2019]

Phrenic nerve stimulation (PNS) is a rare but notable complication that can occur after pacemaker implantation, as demonstrated in a case involving an 88-year-old man with abdominal contractions linked to his pacemaker.

The issue was successfully resolved by adjusting the pacemaker settings noninvasively, highlighting that while PNS can be difficult to diagnose, it can be effectively managed without invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation, a rare complication of pacemaker: A case report. Dalex, M., Malezieux, A., Parent, T., et al.[2023]

In a study of patients with pacing-induced cardiomyopathy (PICM) undergoing cardiac resynchronization therapy (CRT), His bundle pacing (HBP) was successful in 83% of cases and resulted in a greater reduction in QRS duration compared to biventricular pacing (BVP), indicating better electrical synchronization of the heart.

Patients receiving HBP showed more significant improvements in clinical outcomes, including a higher rate of improvement in New York Heart Association (NYHA) class and a greater increase in left ventricular ejection fraction (LVEF) compared to those receiving BVP, suggesting that HBP may be a more effective treatment option for PICM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of His Bundle Pacing Compared to Classic Resynchronization Therapy in Patients with Pacing-Induced Cardiomyopathy. Gardas, R., Golba, KS., Soral, T., et al.[2023]

The use of percutaneous ventricular assist devices (pVAD) has grown significantly in the last decade, but there is still a lack of substantial evidence regarding their impact on patient outcomes.

An expert panel has developed a clinical consensus statement to provide practical management guidelines for pVAD patients in intensive care, addressing key areas such as timing, duration of support, and management of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Step by step daily management of short-term mechanical circulatory support for cardiogenic shock in adults in the intensive cardiac care unit: a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology SC, the European Society of Intensive Care Medicine, the European branch of the Extracorporeal Life Support Organization, and the European Association for Cardio-Thoracic Surgery. Møller, JE., Sionis, A., Aissaoui, N., et al.[2023]

Cardiac resynchronization therapy using a biventricular pacemaker or defibrillator is effective for 50-80% of patients with systolic heart failure who meet specific criteria, including severe symptoms and low ejection fraction.

To enhance treatment outcomes, strategies such as careful patient selection, optimal lead positioning, and device optimization are recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of cardiac resynchronization therapy for treatment of heart failure]. Berney Lamielle, M., Burri, H.[2009]

Cardiac resynchronization therapy is an effective non-drug treatment for patients with dilated cardiomyopathy and congestive heart failure, relying on consistent biventricular stimulation for success.

In an 84-year-old patient, intermittent loss of biventricular pacemaker stimulation was resolved by adjusting programming parameters, highlighting the importance of proper device management in therapy effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Loss of biventricular resynchronization due to an uncommon cause: Report of one case]. Vergara S, I., Frangini S, P., González, R., et al.[2019]

Biventricular pacing, also known as cardiac resynchronization therapy, has been shown to improve clinical outcomes in patients with systolic heart failure and ventricular conduction delays, suggesting its efficacy in correcting ventricular dyssynchrony.

The review highlights the potential benefits of optimizing biventricular pacing techniques, particularly through sequential pacing (adjusting the timing between right and left ventricular stimulation) compared to the standard simultaneous pacing, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventricular optimization of biventricular pacing: a systematic review. Lim, SH., Lip, GY., Sanderson, JE.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats. [2016]

2. Germany pubmed.ncbi.nlm.nih.gov

Diaphragm pacing with natural orifice transluminal endoscopic surgery: potential for difficult-to-wean intensive care unit patients. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Phrenic Nerve Stimulator Placement via the Cervical Approach: Technique and Anatomic Considerations. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Minimal invasive coronary sinus lead reposition technique for the treatment of phrenic nerve stimulation. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Temporary Transvenous Diaphragmatic Neurostimulation in Prolonged Mechanically Ventilated Patients: A Feasibility Trial (RESCUE 1). [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation? [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

[Diaphragm pacing with a spinal cord stimulator]. [2006]

8. United States pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation for diaphragm pacing with a spinal cord stimulator: technical note. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

[Implantation of a phrenic stimulator in central respiratory paralysis]. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation, a rare complication of pacemaker: A case report. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of His Bundle Pacing Compared to Classic Resynchronization Therapy in Patients with Pacing-Induced Cardiomyopathy. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Step by step daily management of short-term mechanical circulatory support for cardiogenic shock in adults in the intensive cardiac care unit: a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology SC, the European Society of Intensive Care Medicine, the European branch of the Extracorporeal Life Support Organization, and the European Association for Cardio-Thoracic Surgery. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

[Role of cardiac resynchronization therapy for treatment of heart failure]. [2009]

14. Chile pubmed.ncbi.nlm.nih.gov

[Loss of biventricular resynchronization due to an uncommon cause: Report of one case]. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Ventricular optimization of biventricular pacing: a systematic review. [2018]