Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.

Sepsis Clinical Trial

— SNV-Sepsis  

Official title:

Randomized Pilot Study Evaluating the Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04774705
• Other study ID #: D20170804
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2021
• Est. completion date: March 29, 2023

Study information

• Verified date: June 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Eric AZABOU
• Phone: +331 47 10 79 40
• Email: eric.azabou[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sepsis is one of the leading causes of death in intensive care. About 50% of patients with septic shock die after 1 year; and 50% of survivors suffer from cognitive decline. The pathophysiological mechanisms of serious complications of sepsis are now well known. In fact, the systemic inflammation related to sepsis amplifies the release of pro-inflammatory cytokines and neurotoxic mediators, hence an increase in deleterious phenomena such as oxidative stress, mitochondrial dysfunction, endothelial activation, disruption of the blood-brain barrier, neuroinflammation (astrocytic and microglial activation) leading to multi-organ failure which compromises the patient's vital and functional prognosis. Although there has been progress in the understanding of its pathophysiology, the management of sepsis and septic shock in intensive care relies mainly on anti-infective treatments and the restoration of cardiovascular and respiratory functions. There is virtually no adjuvant therapy for the management of sepsis, apart from a few hormonal therapies such as insulin to maintain blood glucose levels below 180 mg / dL and low doses of corticosteroids and vasopressin. There is therefore a pressing need to develop innovative treatments targeting inflammatory and immunological processes in order to reduce the complications of sepsis and improve patient prognosis. Some recent work has shown that electrical vagus nerve stimulation (SNV), a technique used for the treatment of drug-resistant epilepsy, can modulate inflammatory and immune responses and control inflammation syndrome in animal models of sepsis, arthritis and rheumatism in humans. In this pilot study the investigators plan to evaluate the efficacy of transcutaneous (non-invasive) SNV as an adjuvant treatment in patients with sepsis in intensive care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 29, 2023
• Est. primary completion date: March 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age> 18 years old

• Adult man or woman, hospitalized in intensive care, presenting with sepsis for at least 24 hours according to the diagnostic criteria (Singer et al., 2016).

Exclusion Criteria:

• Patient under guardianship,

• Patient in a severe state of agitation.

• Patient in a state of brain death or active limitation of treatment.

• Multiple trauma patient, with multiple fractures of the skull.

• Refusal to participate in the study or to sign the informed consent by the patient or his loved one,

• Pregnant or breastfeeding woman,

• No affiliation to a social security scheme.

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Toxemia

Intervention

Other:
• SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )
A transcutaneous stimulator of the atrial branch of the vagus nerve of the TENS eco Plus type (Schwa-medico) will be used. SNV stimulation will be applied in the concha of the left ear to the subcutaneous area of the atrial branch of the vagus nerve in the left ear (cymba conchae) for each patient, at an intensity of 2 mA, 30 minutes per day for 5 consecutive days, from the day of inclusion / randomization.
• Placebo group
For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.

Locations

Country	Name	City	State
France	Raymond Poincaré Hospital	Garches

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Overall death	at day 90
Secondary	Cumulative incidence of delirium and its duration		up to day 90
Secondary	Cumulative incidence of mechanical ventilation and its duration		up to day 90
Secondary	Proportion of patients having been the subject of a decision to limit or withdraw care		at day 90
Secondary	Duration of use of vasopressors		at day 90
Secondary	Number of days alive with a SOFA score <6		at day 90
Secondary	Length of stay in intensive care and hospitalization in all patients and in survivors		at day 90
Secondary	Measurements of changes in C-reactive protein (CRP)		at inclusion
Secondary	Measurements of changes in C-reactive protein (CRP)		at day 7
Secondary	Measurements of changes in C-reactive protein (CRP)		at day 14
Secondary	Measurements of changes in C-reactive protein (CRP)		at day 21
Secondary	Measurements of changes in C-reactive protein (CRP)		at day 28
Secondary	Measurements of changes in C-reactive protein (CRP)		at day 90
Secondary	Measurements of changes in fibrinogen level		at inclusion
Secondary	Measurements of changes in fibrinogen level		at day 7
Secondary	Measurements of changes in fibrinogen level		at day 14
Secondary	Measurements of changes in fibrinogen level		at day 21
Secondary	Measurements of changes in fibrinogen level		at day 28
Secondary	Measurements of changes in fibrinogen level		at day 90
Secondary	Measurements of changes in interleukin-6 (IL-6)		at inclusion
Secondary	Measurements of changes in interleukin-6 (IL-6)		at day 7
Secondary	Measurements of changes in interleukin-6 (IL-6)		at day 14
Secondary	Measurements of changes in interleukin-6 (IL-6)		at day 21
Secondary	Measurements of changes in interleukin-6 (IL-6)		at day 28
Secondary	Measurements of changes in interleukin-6 (IL-6)		at day 90
Secondary	Measurements of changes in interleukin-1ß (IL-1ß)		at inclusion
Secondary	Measurements of changes in interleukin-1ß (IL-1ß)		at day 7
Secondary	Measurements of changes in interleukin-1ß (IL-1ß)		at day 14
Secondary	Measurements of changes in interleukin-1ß (IL-1ß)		at day 21
Secondary	Measurements of changes in interleukin-1ß (IL-1ß)		at day 28
Secondary	Measurements of changes in interleukin-1ß (IL-1ß)		at day 90
Secondary	Measurements of changes in tumor necrosis factor a (TNF-a)		at inclusion
Secondary	Measurements of changes in tumor necrosis factor a (TNF-a)		at day 7
Secondary	Measurements of changes in tumor necrosis factor a (TNF-a)		at day 14
Secondary	Measurements of changes in tumor necrosis factor a (TNF-a)		at day 21
Secondary	Measurements of changes in tumor necrosis factor a (TNF-a)		at day 28
Secondary	Measurements of changes in tumor necrosis factor a (TNF-a)		at day 90
Secondary	Measurements of changes in the calcium binding protein B S100B (S100B)		at inclusion
Secondary	Measurements of changes in the calcium binding protein B S100B (S100B)		at day 7
Secondary	Measurements of changes in the calcium binding protein B S100B (S100B)		at day 14
Secondary	Measurements of changes in the calcium binding protein B S100B (S100B)		at day 21
Secondary	Measurements of changes in the calcium binding protein B S100B (S100B)		at day 28
Secondary	Measurements of changes in the calcium binding protein B S100B (S100B)		at day 90
Secondary	Measurements of changes in the arterial lactate level		at inclusion
Secondary	Measurements of changes in the arterial lactate level		at day 7
Secondary	Measurements of changes in the arterial lactate level		at day 14
Secondary	Measurements of changes in the arterial lactate level		at day 21
Secondary	Measurements of changes in the arterial lactate level		at day 28
Secondary	Measurements of changes in the arterial lactate level		at day 90
Secondary	Characteristics of the EEG		at inclusion
Secondary	Characteristics of the EEG		at day 7
Secondary	Mortality rate	Overall death	at day 28
Secondary	Neurological fate of patients	Neurological fate of patients will evaluated using Glasgow Outcome Scale - GOS	at day 90