Clinical trial NCT04774705: Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sepsis
Septic Shock
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-03-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mortality
timeFrame: at day 90
Secondary outcomes:
measure: Cumulative incidence of delirium and its duration
timeFrame: up to day 90
measure: Cumulative incidence of mechanical ventilation and its duration
timeFrame: up to day 90
measure: Proportion of patients having been the subject of a decision to limit or withdraw care
timeFrame: at day 90
measure: Duration of use of vasopressors
timeFrame: at day 90
measure: Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6
timeFrame: at day 90
measure: Length of stay in intensive care and hospitalization in all patients and in survivors
timeFrame: at day 90
measure: Measurements of changes in C-reactive protein (CRP)
timeFrame: at inclusion
measure: Measurements of changes in C-reactive protein (CRP)
timeFrame: at day 7
measure: Measurements of changes in C-reactive protein (CRP)
timeFrame: at day 14
measure: Measurements of changes in C-reactive protein (CRP)
timeFrame: at day 21
measure: Measurements of changes in C-reactive protein (CRP)
timeFrame: at day 28
measure: Measurements of changes in C-reactive protein (CRP)
timeFrame: at day 90
measure: Measurements of changes in fibrinogen level
timeFrame: at inclusion
measure: Measurements of changes in fibrinogen level
timeFrame: at day 7
measure: Measurements of changes in fibrinogen level
timeFrame: at day 14
measure: Measurements of changes in fibrinogen level
timeFrame: at day 21
measure: Measurements of changes in fibrinogen level
timeFrame: at day 28
measure: Measurements of changes in fibrinogen level
timeFrame: at day 90
measure: Measurements of changes in interleukin-6 (IL-6)
timeFrame: at inclusion
measure: Measurements of changes in interleukin-6 (IL-6)
timeFrame: at day 7
measure: Measurements of changes in interleukin-6 (IL-6)
timeFrame: at day 14
measure: Measurements of changes in interleukin-6 (IL-6)
timeFrame: at day 21
measure: Measurements of changes in interleukin-6 (IL-6)
timeFrame: at day 28
measure: Measurements of changes in interleukin-6 (IL-6)
timeFrame: at day 90
measure: Measurements of changes in interleukin-1β (IL-1β)
timeFrame: at inclusion
measure: Measurements of changes in interleukin-1β (IL-1β)
timeFrame: at day 7
measure: Measurements of changes in interleukin-1β (IL-1β)
timeFrame: at day 14
measure: Measurements of changes in interleukin-1β (IL-1β)
timeFrame: at day 21
measure: Measurements of changes in interleukin-1β (IL-1β)
timeFrame: at day 28
measure: Measurements of changes in interleukin-1β (IL-1β)
timeFrame: at day 90
measure: Measurements of changes in tumor necrosis factor α (TNF-α)
timeFrame: at inclusion
measure: Measurements of changes in tumor necrosis factor α (TNF-α)
timeFrame: at day 7
measure: Measurements of changes in tumor necrosis factor α (TNF-α)
timeFrame: at day 14
measure: Measurements of changes in tumor necrosis factor α (TNF-α)
timeFrame: at day 21
measure: Measurements of changes in tumor necrosis factor α (TNF-α)
timeFrame: at day 28
measure: Measurements of changes in tumor necrosis factor α (TNF-α)
timeFrame: at day 90
measure: Measurements of changes in the calcium binding protein B S100B (S100B)
timeFrame: at inclusion
measure: Measurements of changes in the calcium binding protein B S100B (S100B)
timeFrame: at day 7
measure: Measurements of changes in the calcium binding protein B S100B (S100B)
timeFrame: at day 14
measure: Measurements of changes in the calcium binding protein B S100B (S100B)
timeFrame: at day 21
measure: Measurements of changes in the calcium binding protein B S100B (S100B)
timeFrame: at day 28
measure: Measurements of changes in the calcium binding protein B S100B (S100B)
timeFrame: at day 90
measure: Measurements of changes in the arterial lactate level
timeFrame: at inclusion
measure: Measurements of changes in the arterial lactate level
timeFrame: at day 7
measure: Measurements of changes in the arterial lactate level
timeFrame: at day 14
measure: Measurements of changes in the arterial lactate level
timeFrame: at day 21
measure: Measurements of changes in the arterial lactate level
timeFrame: at day 28
measure: Measurements of changes in the arterial lactate level
timeFrame: at day 90
measure: Characteristics of the EEG
timeFrame: at inclusion
measure: Characteristics of the EEG
timeFrame: at day 7
measure: Mortality rate
timeFrame: at day 28
measure: Neurological fate of patients
timeFrame: at day 90
Other outcomes:
Locations:
city: Garches
country: France
facility: Raymond Poincaré Hospital
Study officials:
References: