敗血症患者におけるエスケタミンの免疫炎症調節
ICUの敗血症患者における全身性炎症および免疫機能に対する鎮静のためのプロポフォールと組み合わせたエスケタミンの効果：単一施設、非盲検、前向き無作為化対照試験
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.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
-
-
Hubei
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Wuhan、Hubei、中国、430022
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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. |
|
介入なし：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). |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Serum concentration of inflammatory cytokines (0 h)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：up to 8 weeks
|
Length of stay in the ICU |
up to 8 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Serum concentration of atrial natriuretic peptide (ANP) (0 h)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：72 hours after study inclusion
|
0-43, higher scores correspond to more severe sepsis |
72 hours after study inclusion
|
|
Mechanical ventilation time after inclusion
時間枠：Up to 8 weeks
|
Patients requiring mechanical ventilation after study inclusion |
Up to 8 weeks
|
|
Total hospital length of stay
時間枠：Through study completion, an average of 2 year
|
Total length of hospital stay |
Through study completion, an average of 2 year
|
|
Infection complications
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：72 hours after study inclusion
|
Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
72 hours after study inclusion
|
協力者と研究者
捜査官
- 主任研究者：Shiying Yuan, PhD, MD、Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- YSY202001
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
IPD 共有時間枠
Six months after the paper was published
IPD 共有アクセス基準
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
IPD 共有サポート情報タイプ
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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