Acute Hypoxemic Respiratory FailureSTIMULUSNCT05465083
Feasibility of Transvenous Phrenic Nerve Stimulation for Diaphragm Protection in Acute Respiratory Failure
A study testing Lungpacer AeroPace Protect System in people with Acute Hypoxemic Respiratory Failure and Diaphragm Injury, run by University Health Network, Toronto at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, Diaphragm Injury, Lung Injury
- What is being tested?
- Lungpacer AeroPace Protect System
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 4 Feb 2023to 10 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Lungpacer AeroPace Protect System
- Medical subject headings
- Respiratory Insufficiency, Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lungpacer AeroPace Protect SystemDevice
AeroPace Catheter will be placed percutaneously into the left internal jugular vein or left subclavian vein and stimulating electrodes mapped for therapy.
| Study group | Role | What they receive |
|---|---|---|
| Lungpacer AeroPace Protect System | Experimental | 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. Receives: Device: Lungpacer AeroPace Protect System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of placing AeroPace Catheter
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.
Measured: 30 days
Safety of AeroPace Catheter
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.
Measured: 30 days
Secondary outcomes (3)
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
Measured: 7 days
The proportion of time that adequate diaphragm activation is maintained during phrenic nerve stimulation and during the absence of phrenic nerve stimulation.
This is defined as the percentage of hours the patient has an Edi ≥ minimum Edi required to maintain Pocc ≤ -5 cm H2O.
Measured: 7 days
The proportion of hours in which the maintenance of diaphragm activation is due to LAPS-PNS rather than endogenous patient respiratory effort.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study start4 Feb 2023
- Primary completion15 Oct 2023
- Study completion10 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Lungpacer Medical Inc.
- Responsible party
- Sponsor
- Investigators
- Ewan Goligher, MD, PhD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05465083
- Sponsor's protocol ID
- 22-5815
- Other IDs
- 21-5516
- Acronym
- STIMULUS
- Status last verified
- Jun 2023
- First submitted
- 15 Jul 2022
- Last updated
- 11 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Morris IS, Bassi T, Castellvi-Font A, Iftikhar A, Roman-Sarita G, Bellissimo CA, Bootjeamjai P, Zhao Z, Thakkar V, Mehta N, Granton J, Brochard L, Ferguson ND, Goligher EC. Diaphragm neurostimulation mitigates the adverse cardiopulmonary effects of positive pressure ventilation. Crit Care. 2026 Feb 28;30(1):182. doi: 10.1186/s13054-026-05870-9.
PubMed 41764523Morris 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.
PubMed 40043207
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Transvenous Phrenic Nerve Stimulation for Diaphragm Protection in Acute Respiratory Failure: the STIMULUS I Clinical Trial
- ClinicalTrials.gov ID
- NCT05465083
- Acronym / sponsor ID
- STIMULUS / 22-5815
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Lungpacer Medical Inc.
- Study start
- 4 Feb 2023 (actual)
- Primary completion
- 15 Oct 2023 (actual)
- Study completion
- 10 Nov 2023 (actual)
- First posted
- 19 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lungpacer AeroPace Protect System | Experimental | Device: Lungpacer AeroPace Protect SystemThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lungpacer AeroPace Protect SystemAeroPace Catheter will be placed percutaneously into the left internal jugular vein or left subclavian vein and stimulating electrodes mapped for therapy. | Device | Lungpacer AeroPace Protect System |
Primary outcome
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.
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.
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Derived from this study: PubMed 41764523Morris IS, Bassi T, Castellvi-Font A, Iftikhar A, Roman-Sarita G, Bellissimo CA, Bootjeamjai P, Zhao Z, Thakkar V, Mehta N, Granton J, Brochard L, Ferguson ND, Goligher EC. Diaphragm neurostimulation mitigates the adverse cardiopulmonary effects of positive pressure ventilation. Crit Care. 2026 Feb 28;30(1):182. doi: 10.1186/s13054-026-05870-9.
- Derived from this study: PubMed 40043207Morris 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ewan Goligher, MD, PhD principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lungpacer AeroPace Protect System in people with Acute Hypoxemic Respiratory Failure and Diaphragm Injury, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of placing AeroPace Catheter (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05465083, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.