Impact of Auricular Vagus Nerve Neuromodulation on COVID-19 Positive Inpatients Outcome

Study Overview
=================
Brief Summary
-----------------
The COVID-19 pandemic has already overwhelmed the sanitary capacity. Additional therapeutic arsenals, albeit untested in the given context but previously proven to be efficacious in a related clinical context, that could reduce the morbidity rate are urgently needed. A decrease of Heart Rate Variability (HRV) is a validated bad prognosis marker in sepsis and acute respiratory distress syndrome. In contrast, auricular vagus nerve stimulation was proven not only to increase HRV values in healthy Humans, but also to reduce sepsis and increase survival, both significantly, in experimental models. Moreover, the heavy viral infection within the brainstem of deceased patients suggests that the neuroinvasive potential of SARS-CoV2 is likely to be partially responsible for COVID-19 acute respiratory failure and may bear relevance in tailoring future treatment modalities. Interestingly, the vagus nerve (or tenth cranial nerve) connects bidirectionally the brainstem to various internal organs including the lung and to one external organ, namely, the outer ear. Hence, the impact of auricular vagus nerve stimulation through semi-permanent needles will be studied, mostly used so far for pain alleviation, on the outcome of COVID-19 inpatients within 15 days.

Official Title
-----------------
Randomized Double Blinded Monocentric Clinical Trial to Assess the Impact of Auricular Vagus Nerve Neuromodulation in COVID-19 Positive Inpatients Outcome.

Conditions
-----------------
Covid19, SARS-CoV Infection

Intervention / Treatment
-----------------
* Procedure: Auricular neuromodulation
* Procedure: Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: COVID-19 positive inpatient (PCR or other certified test mandatory) Inpatient showing at least one of the following criterion: Abnormal respiratory auscultation AND SpO2 < 94% without oxygen therapy, OR Acute Respiratory failure requiring either oxygen therapy or high-flow oxygen therapy or non-invasive respirator and/or invasive respirator. Exclusion Criteria: Inpatient requiring legal protection Pregnant or breastfeeding woman Intensive care inpatient or patient undergoing surgery Secondary non inclusion criteria : - Unintentional blinding removal.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Auricular neuromodulation<br> | Procedure: Auricular neuromodulation<br>* The pose is carried out by the principal investigator, alone, without the presence of the nursing staff in the room. Ear disinfection and sterile neuromodulation needle placement (service protocol with Chlorhexidine) Placement of 4 semi-permanent Classic needles (SEDATELEC®) on each ear flap at the level of the concha (innervated by the vagus nerve) according to an order and a precise location (4 cardinal points conch), i.e. 8 needles per patient. Compress soaked with Oxygenated water on the concha (to stop potential bleeding). Placing an opaque dressing on the ear and a non-occlusive Band-Aid<br>* Other names: VERUM;|
| Sham Comparator: Control<br> | Procedure: Control<br>* The pose is carried out by the principal investigator, alone, without the presence of the nursing staff in the room. Ear disinfection and sterile manipulation without needle placement (service protocol with Chlorhexidine) No needle laying but only sterile disinfection and pressure over the 4 putative locations with the sterile plastic tip (without the needle). Compress soaked with Oxygenated water on the concha. Placing an opaque dressing on the ear and a non-occlusive Band-Aid.<br>* Other names: SHAM;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the percentage of clinically improved inpatients between D0 and D14 | Inpatients are considered as clinically improved if they have gained at least 2 points on the following clinical evaluation scale, or if they went back home Clinical evaluation scale :1. Outpatient back to normal activities / 2. Outpatient without normal activities / 3. Inpatient without oxygen therapy / 4. Inpatient with oxygen therapy/ 5. Inpatient requiring either nasal high-flow oxygen therapy or non-invasive respirator or both / 6. Inpatient, requiring either ExtraCorporeal Membrane Oxygenation (ECMO) or invasive artificial respirator, or both / 7. Deceased. | 14 day after intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-invasive Neuromodulation, Vagus Nerve