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Régulation immuno-inflammatoire de l'eskétamine chez les patients septiques

Effets de l'eskétamine associée au propofol pour la sédation sur l'inflammation systémique et la fonction immunitaire chez les patients septiques en soins intensifs : un essai contrôlé randomisé prospectif, monocentrique, non aveugle

Studies have shown that excessive systemic inflammatory response and concomitant immunosuppression are the main cause of early death in patients with sepsis. Therefore, it is very important to reduce excessive inflammation and improve immunosuppression in the acute phase of sepsis. Clinical studies have shown that esketamine combined with propofol for sedation has been proven to be safe and effective for septic patients in the ICU due to its cardiovascular stability. Previous studies have demonstrated that esketamine has anti-inflammatory effects against depression and surgical stress. Our preliminary experimental studies have found that esketamine had strong anti-inflammatory effects in the acute phase of sepsis. However, it is not clear whether esketamine could reduce excessive inflammation and improve immunosuppression in septic patients primarily sedated with a continuous infusion of propofol.

This intervention study is to investigate whether three consecutive days of intravenous esketamine infusions via infusion pump (0.07 mg/kg/h) could reduce excessive inflammation and improve immunosuppression in septic patients requiring mechanical ventilation in the ICU under sedation primarily with propofol.

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

10

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Hubei
      • Wuhan, Hubei, Chine, 430022
        • Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 80 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • 18 years old ≤ age ≤60 years old;
  • SOFA score ≥2;
  • Mechanical ventilation should be required for at least 24 hours when included in the study;
  • Informed consent is obtained.

Exclusion Criteria:

  • Age < 18 years old or ≥ 60 years old;
  • Previous solid organ or bone marrow transplantation;
  • Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), or hematologic malignancies (leukemia and lymphoma, etc.);
  • Received radiotherapy or chemotherapy within the past 30 days, or received immunosuppressant drugs (tripterygium wilfordii, mycophenolate mofetil, cyclophosphamide, FK506, etc.), or continuous treatment with prednisolone more than 10 mg/day (or equivalent doses of the other hormones);
  • Unstable angina pectoris or myocardial infarction in the past six months;
  • Acute brain injury (traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, acute intracranial hemorrhage, acute intracranial infection, etc.);
  • Poorly controlled hypertension and congestive heart failure;
  • Increased intraocular or intracranial pressure;
  • Chronic kidney disease, received continuous renal replacement therapy in the past 30 days, or acute renal failure requiring CRRT;
  • Severe chronic liver disease (Child-Pugh class B or C);
  • Alcohol dependence, mental illness or severe cognitive impairment;
  • Pregnancy or lactation;
  • Informed consent is not obtained.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Seul

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: esketamine plus propofol

After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2).

After inclusion, septic patients will be received a single intravenous injection of esketamine (0.7 mg/kg), and then followed by an intravenous administration of esketamine (0.07 mg/kg/h) with an infusion pump for three consecutive days.

After inclusion, septic patients will be received a single intravenous injection of esketamine (0.7 mg/kg), and then followed by an intravenous administration of esketamine (0.07 mg/kg/h) with an infusion pump for three consecutive days.

Aucune intervention: propofol

After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2).

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Serum concentration of inflammatory cytokines (0 h)
Délai: 0 hour after study inclusion

Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-10, IL-17A, and interferon (IFN)-γ

0 hour after study inclusion
Serum concentration of inflammatory cytokines (48 h)
Délai: 48 hours after study inclusion

IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ

48 hours after study inclusion
Serum concentration of inflammatory cytokines (72 h)
Délai: 72 hours after study inclusion

IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ

72 hours after study inclusion
Absolute number of lymphocyte subsets in the peripheral blood (0 h)
Délai: 0 hour after study inclusion

CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells

0 hour after study inclusion
Absolute number of lymphocyte subsets in the peripheral blood (48 h)
Délai: 48 hours after study inclusion

CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells

48 hours after study inclusion
Absolute number of lymphocyte subsets in the peripheral blood (72 h)
Délai: 72 hours after study inclusion

CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells

72 hours after study inclusion
ICU length of stay
Délai: up to 8 weeks

Length of stay in the ICU

up to 8 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Serum concentration of atrial natriuretic peptide (ANP) (0 h)
Délai: 0 hour after study inclusion

ANP is secreted primarily by atrial cardiomyocytes

0 hour after study inclusion
Serum concentration of atrial natriuretic peptide (ANP) (48h)
Délai: 48 hours after study inclusion

ANP is secreted primarily by atrial cardiomyocytes

48 hours after study inclusion
Serum concentration of atrial natriuretic peptide (ANP) (72h)
Délai: 72 hours after study inclusion

ANP is secreted primarily by atrial cardiomyocytes

72 hours after study inclusion
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Délai: 0 hour after study inclusion

0-67, higher scores correspond to more severe disease and a higher risk of death

0 hour after study inclusion
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Délai: 24 hours after study inclusion

0-67, higher scores correspond to more severe disease and a higher risk of death

24 hours after study inclusion
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Délai: 48 hours after study inclusion

0-67, higher scores correspond to more severe disease and a higher risk of death

48 hours after study inclusion
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Délai: 72 hours after study inclusion

0-67, higher scores correspond to more severe disease and a higher risk of death

72 hours after study inclusion
Sequential organ failure assessment (SOFA) score
Délai: 0 hour after study inclusion

0-43, higher scores correspond to more severe sepsis

0 hour after study inclusion
Sequential organ failure assessment (SOFA) score
Délai: 24 hours after study inclusion

0-43, higher scores correspond to more severe sepsis

24 hours after study inclusion
Sequential organ failure assessment (SOFA) score
Délai: 48 hours after study inclusion

0-43, higher scores correspond to more severe sepsis

48 hours after study inclusion
Sequential organ failure assessment (SOFA) score
Délai: 72 hours after study inclusion

0-43, higher scores correspond to more severe sepsis

72 hours after study inclusion
Mechanical ventilation time after inclusion
Délai: Up to 8 weeks

Patients requiring mechanical ventilation after study inclusion

Up to 8 weeks
Total hospital length of stay
Délai: Through study completion, an average of 2 year

Total length of hospital stay

Through study completion, an average of 2 year
Infection complications
Délai: Through study completion, an average of 2 year

Pulmonary infection, urinary tract infection, bloodstream infections, etc

Through study completion, an average of 2 year
In-hospital mortality
Délai: Through study completion, an average of 2 year

Mortality rates for the entire period of hospitalization

Through study completion, an average of 2 year
90-day readmission rate
Délai: Through study completion, an average of 2 year

Percentage of readmission to hospital within 90 days of study inclusion

Through study completion, an average of 2 year
CCL1 expression in alveolar macrophages (0 h)
Délai: 0 hour after study inclusion

CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid

0 hour after study inclusion
CCL1 expression in alveolar macrophages (24 h)
Délai: 24 hours after study inclusion

CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid

24 hours after study inclusion
CCL1 expression in alveolar macrophages (72 h)
Délai: 72 hours after study inclusion

CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid

72 hours after study inclusion
expression of WNT pathway proteins in alveolar macrophages (0 h)
Délai: 0 hour after study inclusion

Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid

0 hour after study inclusion
expression of WNT pathway proteins in alveolar macrophages (24 h)
Délai: 24 hours after study inclusion

Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid

24 hours after study inclusion
expression of WNT pathway proteins in alveolar macrophages (72 h)
Délai: 72 hours after study inclusion

Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid

72 hours after study inclusion

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Les enquêteurs

  • Chercheur principal: Shiying Yuan, PhD, MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

28 juillet 2021

Achèvement primaire (Réel)

1 janvier 2026

Achèvement de l'étude (Réel)

1 janvier 2026

Dates d'inscription aux études

Première soumission

29 mars 2021

Première soumission répondant aux critères de contrôle qualité

11 avril 2021

Première publication (Réel)

14 avril 2021

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

30 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

27 septembre 2026

Dernière vérification

1 juillet 2025

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • YSY202001

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

After the completion of the study, the original data will be sent to the email address: zhjcheng1@163.com, and the password will be provided after the paper is published.

Délai de partage IPD

Six months after the paper was published

Critères d'accès au partage IPD

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Type d'informations de prise en charge du partage d'IPD

  • RSE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .