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NCT Number: NCT04774705

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

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Raymond Poincaré Hospital

Garches, France

Location status: Recruiting

Location contact

Eric AZABOU

CONTACT

+331 47 10 79 40

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Placebo Group

Other

For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.

Primary outcomes

  1. Mortality

    Time frame: at day 90

    Overall death

Secondary outcomes

  1. Cumulative incidence of delirium and its duration

    Time frame: up to day 90

  2. Cumulative incidence of mechanical ventilation and its duration

    Time frame: up to day 90

  3. Proportion of patients having been the subject of a decision to limit or withdraw care

    Time frame: at day 90

  4. Duration of use of vasopressors

    Time frame: at day 90

  5. Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6

    Time frame: 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

  6. Length of stay in intensive care and hospitalization in all patients and in survivors

    Time frame: at day 90

  7. Measurements of changes in C-reactive protein (CRP)

    Time frame: at inclusion

  8. Measurements of changes in C-reactive protein (CRP)

    Time frame: at day 7

  9. Measurements of changes in C-reactive protein (CRP)

    Time frame: at day 14

  10. Measurements of changes in C-reactive protein (CRP)

    Time frame: at day 21

  11. Measurements of changes in C-reactive protein (CRP)

    Time frame: at day 28

  12. Measurements of changes in C-reactive protein (CRP)

    Time frame: at day 90

  13. Measurements of changes in fibrinogen level

    Time frame: at inclusion

  14. Measurements of changes in fibrinogen level

    Time frame: at day 7

  15. Measurements of changes in fibrinogen level

    Time frame: at day 14

  16. Measurements of changes in fibrinogen level

    Time frame: at day 21

  17. Measurements of changes in fibrinogen level

    Time frame: at day 28

  18. Measurements of changes in fibrinogen level

    Time frame: at day 90

  19. Measurements of changes in interleukin-6 (IL-6)

    Time frame: at inclusion

  20. Measurements of changes in interleukin-6 (IL-6)

    Time frame: at day 7

  21. Measurements of changes in interleukin-6 (IL-6)

    Time frame: at day 14

  22. Measurements of changes in interleukin-6 (IL-6)

    Time frame: at day 21

  23. Measurements of changes in interleukin-6 (IL-6)

    Time frame: at day 28

  24. Measurements of changes in interleukin-6 (IL-6)

    Time frame: at day 90

  25. Measurements of changes in interleukin-1β (IL-1β)

    Time frame: at inclusion

  26. Measurements of changes in interleukin-1β (IL-1β)

    Time frame: at day 7

  27. Measurements of changes in interleukin-1β (IL-1β)

    Time frame: at day 14

  28. Measurements of changes in interleukin-1β (IL-1β)

    Time frame: at day 21

  29. Measurements of changes in interleukin-1β (IL-1β)

    Time frame: at day 28

  30. Measurements of changes in interleukin-1β (IL-1β)

    Time frame: at day 90

  31. Measurements of changes in tumor necrosis factor α (TNF-α)

    Time frame: at inclusion

  32. Measurements of changes in tumor necrosis factor α (TNF-α)

    Time frame: at day 7

  33. Measurements of changes in tumor necrosis factor α (TNF-α)

    Time frame: at day 14

  34. Measurements of changes in tumor necrosis factor α (TNF-α)

    Time frame: at day 21

  35. Measurements of changes in tumor necrosis factor α (TNF-α)

    Time frame: at day 28

  36. Measurements of changes in tumor necrosis factor α (TNF-α)

    Time frame: at day 90

  37. Measurements of changes in the calcium binding protein B S100B (S100B)

    Time frame: at inclusion

  38. Measurements of changes in the calcium binding protein B S100B (S100B)

    Time frame: at day 7

  39. Measurements of changes in the calcium binding protein B S100B (S100B)

    Time frame: at day 14

  40. Measurements of changes in the calcium binding protein B S100B (S100B)

    Time frame: at day 21

  41. Measurements of changes in the calcium binding protein B S100B (S100B)

    Time frame: at day 28

  42. Measurements of changes in the calcium binding protein B S100B (S100B)

    Time frame: at day 90

  43. Measurements of changes in the arterial lactate level

    Time frame: at inclusion

  44. Measurements of changes in the arterial lactate level

    Time frame: at day 7

  45. Measurements of changes in the arterial lactate level

    Time frame: at day 14

  46. Measurements of changes in the arterial lactate level

    Time frame: at day 21

  47. Measurements of changes in the arterial lactate level

    Time frame: at day 28

  48. Measurements of changes in the arterial lactate level

    Time frame: at day 90

  49. Characteristics of the EEG

    Time frame: at inclusion

  50. Characteristics of the EEG

    Time frame: at day 7

  51. Mortality rate

    Time frame: at day 28

    Overall death

  52. Neurological fate of patients

    Time frame: at day 90

    Neurological fate of patients will evaluated using Glasgow Outcome Scale (GOS)

Study contacts

Contact information is provided by the study sponsor or research team.

Eric AZABOU

CONTACT

[email protected]

+331 47 10 79 40

Matthieu Resche-Rigon

CONTACT

[email protected]

+33142499742

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: SNV-Sepsis

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Mar 1, 2021
Registry last updated
Jul 17, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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