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Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients

Primary Purpose

Severe Acute Respiratory Syndrome Coronavirus 2

Status
Completed
Phase
Not Applicable
Locations
Argentina
Study Type
Interventional
Intervention
Transcutaneous Auricular Vagus Nerve Stimulation
Sponsored by
Nemechek Technologies
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Acute Respiratory Syndrome Coronavirus 2 focused on measuring vagus nerve stimulation, COVID-19, Acute Respiratory Distress Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients who are 18 years of age
  2. Tested positive or suspected/presumed positive for COVID-19 infection
  3. Patients requiring hospital admission moderate to severe pneumonia and pneumopathy
  4. Patients showing fever and respiratory symptoms with radiological findings of pneumonia
  5. Respiratory distress (≧30 breaths/ min) or Oxygen saturation ≤93% at rest in ambient air; or oxygen saturation ≤97 % with O2 > 5L/min
  6. Patient is able to provide signed and witnessed Informed Consent

Exclusion Criteria:

  1. Already enrolled in a trial for COVID-19 therapy
  2. Potentially life threatening heart rhythm
  3. Pregnancy or potential pregnancy
  4. Current implantation of an electrical and/or neurostimulator device, including but not limited to a cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant
  5. History of aneurysm, intracranial hemorrhage, brain tumors, or significant head trauma
  6. Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised (e.g. homeless, developmentally disabled and prisoner)

Sites / Locations

  • Hospital Zonal Virgen del Carmen de Zárate

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention Arm

Arm Description

Adults over 18 years of age hospitalized because of COVID-19 infection will be treated with transcutaneous auricular vagus nerve stimulation (taVNS).

Outcomes

Primary Outcome Measures

Survival without need of mechanical ventilation
Survival
Cumulative incidence of successful tracheal extubation at day 14 since symptom onset.
Successful tracheal extubation

Secondary Outcome Measures

Survival at day 14 of hospitalization
Survival
Duration of hospitalization
Duration of hospitalization

Full Information

First Posted
May 5, 2020
Last Updated
June 1, 2021
Sponsor
Nemechek Technologies
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1. Study Identification

Unique Protocol Identification Number
NCT04379037
Brief Title
Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients
Official Title
Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
June 27, 2020 (Actual)
Primary Completion Date
September 1, 2020 (Actual)
Study Completion Date
November 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nemechek Technologies

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This trial is designed to determine if the inflammation modulating effect of vagus nerve stimulation can improve pulmonary function and limit progression to ARDS in hospitalized COVID-19 hospitalized patients.
Detailed Description
Patients hospitalized with COVID-19 predominantly die of organ failure due to a surge of pro-inflammatory cytokines triggering the need for mechanical ventilation, often due to acute respiratory distress syndrome (ARDS). Known as a cytokine storm, the surge in cytokines is similar to the excessive inflammatory reaction associated with septic shock. Anti-viral agents will most likely be required to reduce the molecular viral burden in COVID-19 patients, but an additional approach to control the damaging cytokine release is required to alter the course of disease in hospitalized patients and improve chances of survival. Immunosuppressant drugs may reduce inflammation and the tissue damaging cytokines, but they could also be detrimental by inhibiting natural anti-viral immune responses (i.e., suppression of interferons), thereby delaying viral clearance and increasing the risk of secondary infections and death. The reason for the severity of the disease course in some individuals may lie in the regulation of the immune system by the vagus nerve. The vagus nerve is involved in an inflammation controlling reflex similar to the blood pressure regulating baroreflex. The vagus inflammatory reflex is triggered when the afferent vagus nerve senses inflammatory products through peripheral receptors. Vagus nerve activity is relayed through the central nervous system to the efferent vagus nerve. This pathway involves the splenic nerve, which when activated releases norepinephrine and results in suppression of pro-inflammatory cytokine production by macrophages and alleviates inflammation in many pathological settings (e.g., endotoxemia, peritonitis, or acute kidney injury). Electrical stimulation of the vagus nerve using VNS can improve the body's natural ability to regulate the inflammatory response and may be potent enough to suppress pro-inflammatory cytokines and prevent death from COVID-19, especially if used early enough in the course of hospitalization. In rat models of sepsis, VNS attenuates the release of pro-inflammatory cytokines, prevents hypotension, modulates coagulation, and prevents fibrinolysis activation, decreasing organ dysfunction, and improving survival. Human studies also demonstrate that VNS suppresses the production of pro-inflammatory cytokines and improves clinical symptoms in rheumatoid arthritis, intractable epilepsy, atrial fibrillation, and Crohn's Disease. This suggests that VNS may be effective in treating disorders characterized by cytokine dysregulation and that it has the potential to prevent hospitalized patients with COVID-19 from progressing to respiratory failure and death.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Acute Respiratory Syndrome Coronavirus 2
Keywords
vagus nerve stimulation, COVID-19, Acute Respiratory Distress Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
The objective of this study is to determine the therapeutic effect of transcutaneous vagus nerve stimulation in patients with moderate, severe or critical pneumonia associated with Coronavirus Disease 2019 (COVID-19).
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention Arm
Arm Type
Experimental
Arm Description
Adults over 18 years of age hospitalized because of COVID-19 infection will be treated with transcutaneous auricular vagus nerve stimulation (taVNS).
Intervention Type
Device
Intervention Name(s)
Transcutaneous Auricular Vagus Nerve Stimulation
Intervention Description
Transcutaneous vagus nerve stimulation involves stimulating the auricular branch of the vagus nerve with a imperceptible electrical current within the concha of the ear.
Primary Outcome Measure Information:
Title
Survival without need of mechanical ventilation
Description
Survival
Time Frame
Day 14 since symptom onset
Title
Cumulative incidence of successful tracheal extubation at day 14 since symptom onset.
Description
Successful tracheal extubation
Time Frame
Day 14 since symptom onset
Secondary Outcome Measure Information:
Title
Survival at day 14 of hospitalization
Description
Survival
Time Frame
Day 14
Title
Duration of hospitalization
Description
Duration of hospitalization
Time Frame
Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who are 18 years of age Tested positive or suspected/presumed positive for COVID-19 infection Patients requiring hospital admission moderate to severe pneumonia and pneumopathy Patients showing fever and respiratory symptoms with radiological findings of pneumonia Respiratory distress (≧30 breaths/ min) or Oxygen saturation ≤93% at rest in ambient air; or oxygen saturation ≤97 % with O2 > 5L/min Patient is able to provide signed and witnessed Informed Consent Exclusion Criteria: Already enrolled in a trial for COVID-19 therapy Potentially life threatening heart rhythm Pregnancy or potential pregnancy Current implantation of an electrical and/or neurostimulator device, including but not limited to a cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant History of aneurysm, intracranial hemorrhage, brain tumors, or significant head trauma Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised (e.g. homeless, developmentally disabled and prisoner)
Facility Information:
Facility Name
Hospital Zonal Virgen del Carmen de Zárate
City
Zárate
State/Province
Buenos Aires
ZIP/Postal Code
B2800DDF
Country
Argentina

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32192578
Citation
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
Results Reference
background
PubMed Identifier
31447643
Citation
Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Istuk N, Sarolic A, Lechner S, Klonowski W, Varoneckas G, Szeles JC. Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective. Front Neurosci. 2019 Aug 9;13:854. doi: 10.3389/fnins.2019.00854. eCollection 2019.
Results Reference
background
PubMed Identifier
32232102
Citation
Tanaka S, Hammond B, Rosin DL, Okusa MD. Neuroimmunomodulation of tissue injury and disease: an expanding view of the inflammatory reflex pathway. Bioelectron Med. 2019 Aug 13;5:13. doi: 10.1186/s42234-019-0029-8. eCollection 2019.
Results Reference
background
PubMed Identifier
32217835
Citation
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
Results Reference
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Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients

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