Non-invasive Vagal Neurostimulation (nVNS) for Traumatic... | NCT04935697

NCT04935697

Status Module

Sponsor/Collaborators Module

Name	Class
ElectroCore INC	INDUSTRY
Chuck Noll Foundation	UNKNOWN

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Receiving Non-invasive vagus neurostimulation	Experimental	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI.	Device: nVNS Other: SOC
Receiving Standard of Care	Other	Patients will be managed according to the institutional best practices and SOC for TBI.	Other: SOC

Name	Type	Description	Arm Group Labels	Other Names
nVNS	Device	3x daily treatment of nVNS + SOC	Receiving Non-invasive vagus neurostimulation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
All-Cause 90-Day Admission to Any Hospital or ED Encounter	A composite endpoint of 90-day presentation to any emergency department and/or 90-day admission to any hospital.	90 days

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With AEs/SAEs Up to 30 Days From Baseline		30 days from baseline
Number of Participants With Abnormal Physical Examination by Day 30		30 days from baseline

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patient is between 12-80 years, inclusive
Patient has been admitted to the hospital for mild-to-moderate TBI that is restricted to the head and/or neck region.
Patient is not on invasive mechanical ventilation
Patient has a mild-to-moderate TBI based on a non-resuscitated or post-resuscitated Glasgow Coma Scale (GCS) sum score of =>12
Patient has a Lung Injury Prediction Score (LIPS) of =>2
Administration of the first nVNS treatment must be planned to take place within 24 h of intake
A signed, written informed consent form from the patient or legally authorized representative

Exclusion Criteria:

Patient has a diagnosis of moderate or greater grade of respiratory distress/ARDS according to the Berlin definition of ARDS: Partial pressure of oxygen (PaO2) /Fraction of Inspired Oxygen (FiO2) > 100 mmHg (>13.3 kPa) to ≤ 200 mmHg (≤ 26.6 kPa) with positive end-expiratory pressure (PEEP) ≥ 5 cmH2O)
Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
Patient simultaneously taking part in another clinical trial
Patient is not expected to survive for 24 hours
Patient has an underlying clinical condition where, in the opinion of the study physicians and the institutional health provider physician, it would be extremely unlikely that the patient would not progress to invasive mechanical ventilation within 48 hours or any other condition that might require immediate invasive mechanical ventilation (e.g. motor neuron disease, Duchenne muscular dystrophy, or rapidly-progressive interstitial pulmonary fibrosis)
Patient has severe chronic obstructive pulmonary disease (COPD) requiring long-term home oxygen therapy or mechanical ventilation (non-invasive ventilation or via tracheotomy) except for continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BIPAP) used solely for sleep-disorder breathing
Patient has congestive heart failure
Patient has acute left ventricular failure
Patient has liver failure (Child-Pugh grade C)
Patient is receiving renal dialysis therapy for chronic renal failure
Patient is receiving extracorporeal membrane oxygenation, high-frequency oscillatory ventilation (HFOV) or any form of extracorporeal lung support
Patient has had any form of mechanical ventilation (invasive or non-invasive, excluding CPAP alone) for longer than 48 h prior to the diagnosis of mild-to-moderate respiratory distress/ARDS
Patient has burns to ≥ 15% of their total body surface area

Contacts/Locations Module

Name	Affiliation	Role
Sarah Kimutis	Allegheny Health Network	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
AHN Allegheny General Hospital		Pittsburgh	Pennsylvania	15212	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Nov 7, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.
BG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0001 BG0012 BG0023

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00041(41 to 41) BG00129(14 to 44) BG00241(14 to 44)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Smoking Status

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Smoker	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

All-Cause 90-Day Admission to Any Hospital or ED Encounter

A composite endpoint of 90-day presentation to any emergency department and/or 90-day admission to any hospital.

Posted

Count of Participants

Participants

90 days

ID	Title	Description
OG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.
OG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.

Units	Counts
Participants	OG0001 OG0012

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Secondary

Number of Participants With AEs/SAEs Up to 30 Days From Baseline

Posted

Count of Participants

Participants

30 days from baseline

ID	Title	Description
OG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.
OG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Physical Examination by Day 30

Posted

Count of Participants

Participants

30 days from baseline

ID	Title	Description
OG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.
OG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Vital Signs by Day 30

Not all outcomes could be analyzed. PaO2/FiO2 ratio data were not available for any patients. Temperature data were only available for a single patient in the arm treated according to standard of care. Blood pressure was assessed for all patients (at additional timepoints for patients who entered the study while hospitalized as compared to those who participated in an outpatient fashion).

Posted

Count of Participants

Participants

30 days from baseline

ID	Title	Description
OG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.
OG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.

Secondary

Number of Participants With Abnormal Laboratory Results by Day 30

Certain visits (during which the standard of care labs were done) were only held for the subgroup of patients that were hospitalized (n=1) at time of enrollment/randomization or for patients not hospitalized at enrollment/randomization but who presented for Visits 2 and 3 (which depended on the date of injury and date of consent). Note that hospitalization at the time of enrollment (and thus inpatient study participation) is unrelated to the primary study outcome of all-cause hospital admission.

Posted

Count of Participants

Participants

30 days from baseline

ID	Title	Description
OG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.
OG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Receiving Non-invasive Vagus Neurostimulation	nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI. nVNS: 3x daily treatment of nVNS + SOC SOC: Standard of care patient management.	0	1	0	1	0	1
EG001	Receiving Standard of Care	Patients will be managed according to the institutional best practices and SOC for TBI. SOC: Standard of care patient management.	0	2	0	2	0	2

Title	Organization	Phone	Extension	Email
Health Outcomes Researcher	Orthopaedic Institute, Allegheny Health Network	412-359-4042		praveer.vyas@ahn.org

First MCP Posted Date

ID	Term
D012128	Respiratory Distress Syndrome
D055371	Acute Lung Injury
D000070642	Brain Injuries, Traumatic

Ancestor Terms

ID	Term
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D012120	Respiration Disorders
D055370	Lung Injury
D001930	Brain Injuries
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D006259	Craniocerebral Trauma
D020196	Trauma, Nervous System
D014947	Wounds and Injuries