Feasibility of Transvenous Phrenic Nerve Stimulation for Diaphragm Protection in Acute Respiratory Failure

NCT ID: NCT05465083

Last Updated: 2024-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-04
• Study Completion Date: 2023-11-10

Brief Summary

This is a single-center proof-of-concept clinical trial designed to establish the feasibility of transvenous phrenic-nerve stimulation (PNS) to maintain diaphragm activation over the first 24 hours and for up to seven days of mechanical ventilation in patients who are likely to require more than 48 hours of invasive mechanical ventilation.

Detailed Description

The diaphragm is the main muscle of breathing and for most of us therefore is continuously being used (and hence exercised) when in health. When people are unwell with severe breathing difficulties to the degree that their lungs are needing a lot of support from a breathing machine (ventilator) in the intensive care unit (ICU), or are recovering from major lung/chest surgery on a ventilator in ICU, the diaphragm can quickly start to weaken from its inactivity. This means that even when starting to recover from the underlying medical problem, or from the surgery itself, the diaphragm may be unable perform well enough to take over the work of breathing once again. This can lead to not only longer times on the ventilator (time to gradually rebuild diaphragm strength by rehabilitation and physiotherapy) but also therefore longer times in ICU and in hospital with the risk of complications that can be associated with this.

Stimulating the diaphragm by use of a pacemaker (electrical stimulation) is an established treatment for a number of patients with certain types of long-term breathing problems. These pacemakers are permanent and are inserted by invasive surgical methods. More recently however, there have also been a number of studies looking to see if it is possible to safely, temporarily and less invasively stimulate the diaphragm of patients who only have temporary diaphragm inactivity. This has been done either during surgery or during their intensive care stay. A number of methods of temporarily stimulating the diaphragm have been looked at, but the simplest has been to integrate the function of stimulating the nerves (that ultimately control the diaphragm) with a catheter that is frequently placed into a vein in the neck to enable delivery of medications during surgery and in ICU.

Conditions

Acute Hypoxemic Respiratory Failure; Diaphragm Injury; Lung Injury

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Lungpacer AeroPace Protect System

The PNS device used for this study will be the most recent AeroPace central venous catheter from Lungpacer Medical Inc (Vancouver, BC). It is an 8.5F 23cm triple lumen central venous catheter with 30 electrodes arranged in two arrays (distal 9 electrodes intended to capture the right phrenic nerve and the 21 proximal to capture the left phrenic nerve). It is inserted via the left internal jugular or left subclavian vein where it is placed in the proximal superior vena cava (SVC) at or above the cavo-atrial junction.

The AeroPace system monitors airway pressure to detect ventilator-triggered controlled mechanical breaths and patient-triggered assisted mechanical breaths. In response to detection of native respiratory efforts the PNS lies quiescent.

Group Type: EXPERIMENTAL

Lungpacer AeroPace Protect System

Intervention Type: DEVICE

AeroPace Catheter will be placed percutaneously into the left internal jugular vein or left subclavian vein and stimulating electrodes mapped for therapy.

Interventions

Lungpacer AeroPace Protect System

AeroPace Catheter will be placed percutaneously into the left internal jugular vein or left subclavian vein and stimulating electrodes mapped for therapy.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years old, and,
• Invasive mechanical ventilation for ≤ 7 days, and,
• Have hypoxemia as defined by one of:
• A PaO2:FiO2 ratio < 300 and PEEP ≥ 5 cm H2O, or
• SpO2:FiO2 < 315% on PEEP ≥ 5 cm H2O in absence of an available arterial blood gas, and in the presence of a reliable Sp)2 trace and a SpO2 < 97%, or
• Are receiving inhaled nitric oxide for acute hypoxemia, or
• Require extracorporeal membrane oxygenation, and,
• Are on controlled mechanical ventilation with no patient-triggered ventilator-delivered breaths with no imminent plan to transition to assisted ventilation within 6 hours, and,
• Are not expected to be liberated from mechanical ventilation within the next 48 hours (from time of enrollment)

Group 2: Pulmonary endarterectomy

• Age 18 to 65 years old
• Are listed for pulmonary thromboendarterectomy
• Have pulmonary vascular resistance < 1000 dynes.sec.cm-5

Group 3: Lung transplant

• Age 18 years or older
• Are listed for bilateral lung transplant for a primary indication of idiopathic pulmonary fibrosis with no plan for concomitant transplant of other solid organs

All groups

Exclusion Criteria

• Pregnant or lactating
• Previously diagnosed neuromuscular disorder or known phrenic nerve injury
• BMI >70kg/m2
• Implanted electronic cardiac or neurostimulation device in situ
• Contraindications to left internal jugular or subclavian vein catheterization (e.g., infection over the site, known central venous stenosis, septic thrombophlebitis, left internal jugular ECMO cannula in situ) and/or subclavian vein catheterization (to include poor target vessel)
• Contraindications to esophageal balloon or EMG catheter placement (e.g. active bleeding or high-grade esophageal varices with recent bleeding or banding in previous 14 days, recent esophageal surgery or esophageal rupture)
• Patient transitioning fully to palliative care
• Treating clinician deem enrollment not clinically appropriate for other reason
• Currently being treated in another clinical trial studying an experimental treatment that could affect the study primary outcome

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lungpacer Medical Inc.

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ewan Goligher, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

University Health Network

Toronto, Ontario, Canada

Countries

Canada

References

Morris IS, Bassi T, Bellissimo CA, Bootjeamjai P, Roman-Sarita G, de Perrot M, Donahoe L, McRae K, Dianti J, Del Sorbo L, Keshavjee S, Cypel M, Reynolds SC, Dres M, Thakkar V, Mehta N, Brochard L, Ferguson ND, Goligher EC. Continuous On-Demand Diaphragm Neurostimulation to Prevent Diaphragm Inactivity During Mechanical Ventilation: A Phase 1 Clinical Trial (STIMULUS). Am J Respir Crit Care Med. 2025 Aug;211(8):1442-1451. doi: 10.1164/rccm.202407-1483OC.

Reference Type: DERIVED

PMID: 40043207 (View on PubMed)

Other Identifiers

21-5516

Identifier Type: OTHER

Identifier Source: secondary_id

22-5815

Identifier Type: -

Identifier Source: org_study_id