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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) | Experimental |
| |
| Control group | Placebo Comparator | For the SNV placebo group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | Overall death | at day 90 |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative incidence of delirium and its duration | up to day 90 | |
| Cumulative incidence of mechanical ventilation and its duration | up to day 90 | |
| Proportion of patients having been the subject of a decision to limit or withdraw care |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eric AZABOU | Contact | +331 47 10 79 40 | eric.azabou@aphp.fr | |
| Matthieu Resche-Rigon | Contact | +33142499742 | matthieu.resche-rigon@univ-paris-diderot.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Raymond Poincaré Hospital | Recruiting | Garches | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40622772 | Derived | Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Dec 1;36(12):2473-2484. doi: 10.1681/ASN.0000000813. Epub 2025 Jul 7. |
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|
| Placebo group | Other | For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule. |
|
| at day 90 |
| Duration of use of vasopressors | at day 90 |
| Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6 | Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function | at day 90 |
| Length of stay in intensive care and hospitalization in all patients and in survivors | at day 90 |
| Measurements of changes in C-reactive protein (CRP) | at inclusion |
| Measurements of changes in C-reactive protein (CRP) | at day 7 |
| Measurements of changes in C-reactive protein (CRP) | at day 14 |
| Measurements of changes in C-reactive protein (CRP) | at day 21 |
| Measurements of changes in C-reactive protein (CRP) | at day 28 |
| Measurements of changes in C-reactive protein (CRP) | at day 90 |
| Measurements of changes in fibrinogen level | at inclusion |
| Measurements of changes in fibrinogen level | at day 7 |
| Measurements of changes in fibrinogen level | at day 14 |
| Measurements of changes in fibrinogen level | at day 21 |
| Measurements of changes in fibrinogen level | at day 28 |
| Measurements of changes in fibrinogen level | at day 90 |
| Measurements of changes in interleukin-6 (IL-6) | at inclusion |
| Measurements of changes in interleukin-6 (IL-6) | at day 7 |
| Measurements of changes in interleukin-6 (IL-6) | at day 14 |
| Measurements of changes in interleukin-6 (IL-6) | at day 21 |
| Measurements of changes in interleukin-6 (IL-6) | at day 28 |
| Measurements of changes in interleukin-6 (IL-6) | at day 90 |
| Measurements of changes in interleukin-1β (IL-1β) | at inclusion |
| Measurements of changes in interleukin-1β (IL-1β) | at day 7 |
| Measurements of changes in interleukin-1β (IL-1β) | at day 14 |
| Measurements of changes in interleukin-1β (IL-1β) | at day 21 |
| Measurements of changes in interleukin-1β (IL-1β) | at day 28 |
| Measurements of changes in interleukin-1β (IL-1β) | at day 90 |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at inclusion |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at day 7 |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at day 14 |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at day 21 |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at day 28 |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at day 90 |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at inclusion |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at day 7 |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at day 14 |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at day 21 |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at day 28 |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at day 90 |
| Measurements of changes in the arterial lactate level | at inclusion |
| Measurements of changes in the arterial lactate level | at day 7 |
| Measurements of changes in the arterial lactate level | at day 14 |
| Measurements of changes in the arterial lactate level | at day 21 |
| Measurements of changes in the arterial lactate level | at day 28 |
| Measurements of changes in the arterial lactate level | at day 90 |
| Characteristics of the EEG | at inclusion |
| Characteristics of the EEG | at day 7 |
| Mortality rate | Overall death | at day 28 |
| Neurological fate of patients | Neurological fate of patients will evaluated using Glasgow Outcome Scale (GOS) | at day 90 |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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