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

Not Applicable

Recruiting

• Conditions: Sepsis; Septic Shock
• Interventions: Other: Placebo group; Other: SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )

• Registration Number: NCT04774705
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-24
• Study First Submitted QC: 2021-02-24
• Study First Posted: 2021-03-01
• Study Start: 2021-03-29
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-17
• Primary Completion: 2025-03-29
• Study Completion: 2025-03-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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).
• Informed consent signed by patient or family member/trusted support person
• In an emergency situation, in the absence of family members/trusted family/trusted support person

Exclusion Criteria

• Patient under guardianship or curatorship
• 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.
• Patient with cochlear implant
• Patient with heart disease
• Patient with asthma

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Placebo group	For the SNV placebo group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.
SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )	SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )	-

Primary Outcome Measures

Name	Time	Method
Mortality	at day 90	Overall death

Secondary Outcome Measures

Name	Time	Method
Cumulative incidence of delirium and its duration	up to day 90
Cumulative incidence of mechanical ventilation and its duration	up to day 90
Measurements of changes in interleukin-6 (IL-6)	at day 90
Measurements of changes in tumor necrosis factor α (TNF-α)	at day 90
Length of stay in intensive care and hospitalization in all patients and in survivors	at day 90
Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6	at day 90	Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function
Proportion of patients having been the subject of a decision to limit or withdraw care	at day 90
Duration of use of vasopressors	at day 90
Measurements of changes in C-reactive protein (CRP)	at day 90
Measurements of changes in the arterial lactate level	at day 90
Measurements of changes in fibrinogen level	at day 90
Measurements of changes in interleukin-1β (IL-1β)	at day 90
Measurements of changes in the calcium binding protein B S100B (S100B)	at day 90
Characteristics of the EEG	at day 7
Mortality rate	at day 28	Overall death
Neurological fate of patients	at day 90	Neurological fate of patients will evaluated using Glasgow Outcome Scale (GOS)

Trial Locations

Locations (1)

Raymond Poincaré Hospital; 🇫🇷 Garches, France