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

December 10, 2024 updated by: University Health Network, Toronto

Feasibility of Transvenous Phrenic Nerve Stimulation for Diaphragm Protection in Acute Respiratory Failure: the STIMULUS I Clinical Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Group 1: Acute hypoxemic respiratory failure (AHRF)

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

Inclusion Criteria:

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

Group 3: Lung transplant

Inclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Device: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Feasibility of placing AeroPace Catheter
Time Frame: 30 days

Feasibility will be defined as the device being successfully deployed in at least 11 of the 20 patients. Successful deployment of the device defined as:

  • AeroPace Catheter insertion and placement successfully confirmed
  • Initial Catheter electrode mapping/calibration successfully completed
  • Adequate diaphragm activation achieved, defined as hourly Edi level sufficient to generate a Pocc of ≤ -5 cm H2O, for at least 50% of LAPS-PNS stimulated breaths over the first 24 hours after commencing stimulation.
30 days
Safety of AeroPace Catheter
Time Frame: 30 days
The technique will be considered safe if there are no unexpected serious adverse events (USADEs) and the incidence of device- or procedure-related SAEs is below that established in literature.
30 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
LAPS-PNS successfully achieved at the time of the mapping/calibration procedure on each of the subsequent days up to the end of the study intervention period
Time Frame: 7 days
7 days
The proportion of time that adequate diaphragm activation is maintained during phrenic nerve stimulation and during the absence of phrenic nerve stimulation.
Time Frame: 7 days
This is defined as the percentage of hours the patient has an Edi ≥ minimum Edi required to maintain Pocc ≤ -5 cm H2O.
7 days
The proportion of hours in which the maintenance of diaphragm activation is due to LAPS-PNS rather than endogenous patient respiratory effort.
Time Frame: 7 days
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Lungpacer Medical Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ewan Goligher, MD, PhD, University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 4, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 15, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 10, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 15, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 15, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 19, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 11, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 22-5815
  • 21-5516 (Other Identifier: UHN CAPCR Related ID)

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

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lung Injury

Clinical Trials on Lungpacer AeroPace Protect System

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings