Brief Study Description
The objective of this study is to determine the therapeutic effect and tolerance of transcutaneous vagus nerve stimulation in patients with moderate, severe or critical pneumonia associated with Coronavirus Disease 2019 (COVID-19).
The vagus nerve can be electrically stimulated with implantable or transcutaneous methods which significantly reduce of pro-inflammatory cytokines and improve clinical outcome in a variety of medical conditions including inflammatory bowel disease, rheumatoid arthritis and sepsis.
COVID-19 patients appear to have an excessive immunological response and ground-glass chest x-ray findings indicative of inflammatory damage to the lungs. Transcutaneous vagus nerve stimulation suppresses excessive inflammatory reactions and may be useful in controlling the “cytokine storm” that is responsible for ARDS (Acute Respiratory Distress Syndrome) and pulmonary failure observed in COVID-19.
The study will evaluate of 5 minutes of transcutaneous auricular vagus nerve stimulation (taVNS) delivered four times daily to hospitalized COVID-19 patients.
taVNS will be administered to consenting adult patients over 60 years of age hospitalized with COVID-19 and diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. All study subjects will continue to also receive any treatment considered standard of care.
Patients who choose not to receive taVNS will receive standard of care. Outcomes of taVNS plus stand of care treated patients will be compared with outcomes of standard of care only treated patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open label clinical trial|
|Masking:||None (Open Label)|
|Primary Purpose:||Treatment of COVID-19|
|Official Title:||COVID-19 VNS ARDS Prevention Trial|
|Actual Study Start Date :||TBD|
|Estimated Primary Completion Date :||TBD|
|Estimated Study Completion Date :||TBD|
Arms and Interventions
- Single arm, non-controlled, open label
- Transcutaneous auricular vagus nerve stimulation will be administered for 5 minutes every 6 hours for 14 days maximum or until discharge. Electrical contact will be a specialized clip with one contact placed within the concha and the other contact of the clip acting as the grounding element on the back of the ear.
- Stimulation will be set at 5 Hz, 800 mS with voltage set at 10v below the perceptual threshold.
- Standard care including anti-viral and other anti-inflammatory agents will be allowed.
Primary Outcome Measures :
- Survival without need of mechanical ventilation at day 14. [ time frame: 14 days from symptom onset ]
- Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48 h) at day 14. Death or DNR order will be considered a competing negative event.
- WHO progression scale ≤ 7 at day 4 [ time frame: 4 days since admission ]
- WHO progression scale ≤ 5 at day 4 [ time frame: 4 days since admission ]
Secondary Outcome Measures:
- WHO progression scale [ time frame: 7 and 14 days ]
- Survival [ time frame: 14 days ]Overall survival
- 28-day ventilator free-days [ time frame: 28 days ]
- Respiratory Acidosis at day 4 [ time frame: 4 days ]
- Arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
- Time to oxygen supply independency [ time frame: 14 days ]
- Duration of hospitalization [ time frame: 28 days ]
- Time to ICU discharge [ time frame: 28 days ]
- Time to hospital discharge [ time frame: 28 days ]
WHO progression scale:
- 0 – Uninfected; no viral RNA detected
- 1 – Asymptomatic; viral RNA detected
- 2 – Symptomatic; independent
- 3 – Symptomatic; assistance needed
- 4 – Hospitalized; no oxygen therapy
- 5 – Hospitalized; oxygen by mask or nasal prongs
- 6 – Hospitalized; oxygen by NIV or High flow
- 7 – Intubation and mechanical ventilation, pO2/FIO2>=150 or SpO2/FIO2>=200
- 8 – Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) or vasopressors (norepinephrine >0.3 microg/kg/min)
- 9 – Mechanical ventilation, pO2/FIO2<150 and vasopressors (norepinephrine >0.3 microg/kg/min), or Dialysis or ECMO
- 10 – Dead
|Ages Eligible for Study:||60 Years and older|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients requiring hospital admission with documented COVID-19 infection and moderate to severe pneumonia and pneumopathy.
- Patients showing fever and respiratory symptoms with radiological findings of pneumonia.
- Respiratory distress (≧30 breaths/ min);
- Oxygen saturation ≤93% at rest in ambient air; or oxygen saturation ≤97 % with O2 > 5L/min.
- PaO2/FiO2 ≦ 300mmHg
- Known intolerance to vagus nerve stimulation
- Unconscious patient
- Symptomatic bradycardia
- Potentially life threatening heart rhythm.
- Pregnancy or potential pregnancy
Responsible Party Dr. Patrick M Nemechek, D.O.
Contact: +1-623-208-4226, [email protected]