pdSTIM System Therapy for Difficulty Weaning from Mechanical Ventilation

(ReInvigorate Trial)

Recruiting at 19 trial locations

Overseen By Head of Clinical

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stimdia Medical Inc.

Must not be taking: Anticoagulants, Neuromuscular blockades

Disqualifiers: Neurological issues, Hemodynamic instability, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 30 days

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called the pdSTIM System, which aims to help people come off mechanical ventilation more easily by stimulating the phrenic nerve, which controls breathing. The study compares this new therapy with standard care to determine if it can speed up the weaning process and ensure safety. People who have been on a ventilator for at least four days and have previously struggled to wean off are good candidates for this trial. Participants will be randomly assigned to receive either standard care alone or standard care with the pdSTIM System.

As an unphased trial, this study offers participants the chance to contribute to innovative research that could improve future treatment options.

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 prior data suggests that the pdSTIM System is safe for facilitating weaning from mechanical ventilation?

Research has shown that the pdSTIM System, which aids patients in breathing independently by stimulating a nerve in the chest, has promising safety results. In earlier studies, researchers used this system on patients who had been on ventilators for extended periods. These studies found that 96% of patients successfully discontinued mechanical ventilation. Importantly, these trials reported no major safety issues or serious side effects linked to the pdSTIM System.

While researchers continue to study this treatment, current data suggest it is well-tolerated by patients. This is encouraging for those considering joining the trial, as previous evidence supports the safety of the pdSTIM System. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the pdSTIM System Therapy because it offers a novel approach to helping patients who have difficulty weaning off mechanical ventilation. Unlike standard respiratory support methods, the pdSTIM System uses electrical stimulation to activate specific muscles involved in breathing, potentially enhancing the body's ability to regain independent breathing. This technique could lead to quicker recovery times and less dependence on ventilators, distinguishing it from traditional treatments like gradual weaning and respiratory therapy.

What evidence suggests that the pdSTIM System is effective for weaning from mechanical ventilation?

Research has shown that the pdSTIM System, which participants in this trial may receive, might assist patients struggling to stop using breathing machines. Studies have found that the system can stimulate the phrenic nerve, aiding in breathing control, and potentially improving lung function. In one study, 96% of patients experienced successful nerve stimulation, indicating it may enhance lung performance. This type of electrical stimulation might reduce the duration a person requires mechanical ventilation. Early results suggest it could make the process of weaning off mechanical ventilation quicker and safer. ^{1 2 3 4 5}

Who Is on the Research Team?

Steven Conrad, MD,PhD

Principal Investigator

LSU Health Sciences Shreveport

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• pdSTIM System Therapy

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.

How Is the Trial Designed?

Group I: pdSTIM System Therapy Experimental Treatment 1 Intervention

Group II: Standard of Care Active Control 1 Intervention

pdSTIM System Therapy is already approved in United States for the following indications:

Approved in United States as pdSTIM System for:

• Facilitating weaning from mechanical ventilation in mechanically ventilated adults suffering from diaphragmatic dysfunction who have been on mechanical ventilation for ≥ 96 hours and have failed at least one weaning attempt.

Who Is Running the Clinical Trial?

Stimdia Medical Inc.

Lead Sponsor

Trials

2

Recruited

430+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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) 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11295437/

The ReInvigorate Study—phrenic nerve-to-diaphragm ... The ReInvigorate Study is a prospective, multicenter, randomized, controlled clinical trial to evaluate the safety and efficacy of the pdSTIM™ ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05998018

NCT05998018 | Randomized Study of the pdSTIM™ ... Randomized Study of the pdSTIM™ System (Phrenic Nerve to Diaphragm STIMulation) in Failure to Wean Mechanically Ventilated Patients (ReInvigorate).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39095923/

The ReInvigorate Study-phrenic nerve-to-diaphragm ... It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05998018/randomized-study-of-the-pdstimtm-system-phrenic-nerve-to-diaphragm-stimulation-in-failure-to-wean-mechanically-ventilated-patients

Randomized Study of the pdSTIM™ System (Phrenic ... This prospective, multi-center, randomized, controlled clinical trial is being conducted to evaluate the safety and efficacy of the pdSTIM ...

5. stimdia.com stimdia.com/clinical-study/

Clinical Study - Stimdia Medical KEY STUDY RESULTS · 96% success rate with pdSTIM Lead placement to capture the left and right phrenic nerves. · Confirmed ability to synchronize electrical ...