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Esketamine Induction Intubation in ICU Patients.

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ClinicalTrials.gov Identifier: NCT05464979
Recruitment Status : Not yet recruiting
First Posted : July 19, 2022
Last Update Posted : July 19, 2022
Sponsor:
Information provided by (Responsible Party):
Wuhan Union Hospital, China

Tracking Information
First Submitted Date  ICMJE July 14, 2022
First Posted Date  ICMJE July 19, 2022
Last Update Posted Date July 19, 2022
Estimated Study Start Date  ICMJE August 1, 2022
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2022)
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 5 minutes before induction ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 0 hour after induction ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 0 hour after intubation ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 1 minute after intubation ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 5 minutes after intubation ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 10 minutes after intubation ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 30 minutes after intubation ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of systolic blood pressure, diastolic blood pressure and mean arterial pressure [ Time Frame: 60 minutes after intubation ]
    Systolic blood pressure, diastolic blood pressure and mean arterial pressure
  • Level of heart rate and respiratory rate [ Time Frame: 5 minutes before induction ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 0 hour after induction ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 0 hour after intubation ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 1 minute after intubation ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 5 minutes after intubation ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 10 minutes after intubation ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 30 minutes after intubation ]
    Heart rate and respiratory rate
  • Level of heart rate and respiratory rate [ Time Frame: 60 minutes after intubation ]
    Heart rate and respiratory rate
  • Level of pulse oximetry [ Time Frame: 5 minutes before induction ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 0 hour after induction ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 0 hour after intubation ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 1 minute after intubation ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 5 minutes after intubation ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 10 minutes after intubation ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 30 minutes after intubation ]
    Pulse oximetry
  • Level of pulse oximetry [ Time Frame: 60 minutes after intubation ]
    Pulse oximetry
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2022)
  • Doses of epinephrine and norepinephrine [ Time Frame: At 1 hour after intubation ]
    Epinephrine and norepinephrine doses
  • Doses of epinephrine and norepinephrine [ Time Frame: At 24 hours after intubation ]
    Epinephrine and norepinephrine doses
  • Plasma cytokine levels [ Time Frame: On day 3 after intubation ]
    IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α
  • Acute physiology and chronic health evaluation (APACHE) Ⅱ score [ Time Frame: 0 hour after study inclusion ]
    0-67, higher scores correspond to more severe disease and a higher risk of death
  • Acute physiology and chronic health evaluation (APACHE) Ⅱ score [ Time Frame: 1 day after intubation ]
    0-67, higher scores correspond to more severe disease and a higher risk of death
  • Acute physiology and chronic health evaluation (APACHE) Ⅱ score [ Time Frame: 2 days after intubation ]
    0-67, higher scores correspond to more severe disease and a higher risk of death
  • Acute physiology and chronic health evaluation (APACHE) Ⅱ score [ Time Frame: 3 days after intubation ]
    0-67, higher scores correspond to more severe disease and a higher risk of death
  • Acute physiology and chronic health evaluation (APACHE) Ⅱ score [ Time Frame: 7 days after intubation ]
    0-67, higher scores correspond to more severe disease and a higher risk of death
  • Sequential organ failure assessment (SOFA) score [ Time Frame: 0 hour after study inclusion ]
    0-43, higher scores correspond to more severe disease
  • Sequential organ failure assessment (SOFA) score [ Time Frame: 1 day after intubation ]
    0-43, higher scores correspond to more severe disease
  • Sequential organ failure assessment (SOFA) score [ Time Frame: 2 days after intubation ]
    0-43, higher scores correspond to more severe disease
  • Sequential organ failure assessment (SOFA) score [ Time Frame: 3 days after intubation ]
    0-43, higher scores correspond to more severe disease
  • Sequential organ failure assessment (SOFA) score [ Time Frame: 7 days after intubation ]
    0-43, higher scores correspond to more severe disease
  • Hamilton Anxiety Scale (HAMA) Score [ Time Frame: 1 day after extubation ]
    0-29,higher scores correspond to more severe anxiety
  • Hamilton Depression Scale (HAMD) Score [ Time Frame: 1 day after extubation ]
    0-35,higher scores correspond to more severe depression
  • The number of intubation attempts [ Time Frame: At intubation procedure ]
    Intubation times
  • Mechanical ventilation-free time [ Time Frame: 7 days of after inclusion ]
    Time to weaning from invasive mechanical ventilation
  • 28-day ICU and in-hospital mortality [ Time Frame: Up to 28 days after inclusion ]
    Death within 28 days after hospitalization or ICU stay
  • 90-day readmission rates [ Time Frame: Up to 90 days after discharge from hospital ]
    Hospitalized again within 90 days after discharge from hospital.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Esketamine Induction Intubation in ICU Patients.
Official Title  ICMJE Clinical Effects of Esketamine Induction Intubation Versus Conventional Induction Intubation in ICU Patients: a Single-center Randomized Clinical Trial
Brief Summary

Intubation in the intensive care unit (ICU) is usually an emergency. Pathophysiological changes such as shock, respiratory failure, and metabolic acidosis in critically ill patients can significantly increase the incidence of adverse events during intubation.

Studies have shown that esketamine has no significant effect on body metabolism, endocrine system, liver, kidney, intestinal function and coagulation function. In terms of drug metabolism, esketamine has high bioavailability, short half-life, faster and more comfortable recovery of patients, and not only has the advantage of providing stable hemodynamics during endotracheal intubation, but also counteracts the respiratory depression caused by opioids. In addition, esketamine has antidepressant and anti-inflammatory properties. The investigators also found that combined prophylactic and therapeutic use of esketamine could attenuate systemic inflammation and inflammatory multi-organ injury in mice after CLP-induced lethal sepsis.

This project aims to study the clinical effect of esketamine induction intubation and conventional induction intubation in ICU patients.

Detailed Description

Esketamine is the S-enantiomer of ketamine and has been approved for clinical use by the National Medical Products Administration (NMPA) in 2019. Studies have shown that esketamine has no significant effect on metabolism, endocrine system, liver, kidney, intestinal function and coagulation function. It is mainly used in combination with sedatives (such as propofol, etc.) or alone to induce and implement general anesthesia. The phase III clinical study on the application of esketamine in the induction and maintenance of general anesthesia in laparoscopic surgery showed that the recovery time of the esketamine group was significantly shorter than that of the ketamine group when the same clinical anesthesia effect was achieved. Esketamine has the effect of dissociative anesthesia, which can maintain better spontaneous breathing of patients while satisfying outpatient examinations or operations, and this feature helps maintain circulatory stability, especially in patients with shock. Esketamine has sympathomimetic properties. In patients with potentially unstable cardiac disease (eg, septic cardiomyopathy), esketamine is the preferred choice for induction of anesthesia, especially in combination with midazolam. Esketamine is also the preferred choice for anesthesia induction in patients with bronchospasm, which can protect patients from bronchospasm during induction.

Studies have found that esketamine has antidepressant and anti-inflammatory effects in addition to its analgesic, sedative and anesthetic effects. Clinical studies have shown that esketamine (0.25 mg/kg, 40 min infusion time) can rapidly improve the depressive symptoms of patients with treatment-resistant depression. The antidepressant effects of esketamine may be closely related to its anti-inflammatory effect. During cardiopulmonary bypass surgery, anesthesia induction was supplemented with 1-3 mg/kg esketamine, anesthesia maintenance was supplemented with 2-3 mg/kg/h esketamine, anesthesia maintenance time was 283 minutes, the total amount of esketamine was 1580mg on average. Esketamine decreased plasma levels of IL-6 (6 h after opening the aorta) and IL-8 (1 and 6 h after opening the aorta) and increased plasma levels of IL-10 (1 h after opening the aorta). In the investigators' preliminary study on the role of esketamine in systemic inflammation induced by lipopolysaccharide (LPS), the investigators found that in systemic LPS (5 mg/kg)-induced systemic inflammation model, esketamine (10 mg/kg, IP) was administrated twice 24 hours before LPS administration and 10 minutes after LPS administration. The plasma levels of IL-6, IL-17A and interferon γ (IFN-γ) were significantly decreased 24 h after LPS administration in mice. However, the efficacy and safety of esketamine for tracheal intubation in ICU patients is still unclear, and no relevant clinical studies have been reported.

The investigators will include adult patients subjected to tracheal intubation in the ICU strictly according to the inclusion and exclusion criteria to investigate the efficacy and safety of esketamine for tracheal intubation in ICU patients.

Enrolled patients were randomly assigned to two groups: the esketamine intubation group and the conventional intubation group. In esketamine intubation group, esketamine at 0.5-1.0 mg/kg BW and rocuronium bromide at 0.6 mg/kg BW was given intravenously for induction intubation. After the intubation was completed, esketamine was continuously pumped at 0.3-1.5 mg/kg/h to maintain sedation. In conventional intubation group, Midazolam at 0.1mg/kg BW, fentanyl at 1ug/kg BW, rocuronium bromide at 0.6mg/kg BW was given intravenously for induction intubation; After the intubation was completed, sufentanil at 0.1 μg/kg/h was administered for analgesia, and remazolam tosylate at an initial dose of 0.075 mg/kg/h was administered for sedation, and the dose of remazolam tosylate was adjusted according to the RASS score.

Five tubes of venous blood were collected and sent to the laboratory and immunology department of Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, before intubation and 1, 2, 3 and 7 days after intubation, and five tests including blood routine, coagulation, liver function, kidney function, electrolytes, C-reactive protein, myocardial enzyme, BNP, lymphocyte subsets and cytokines were performed. A tube of arterial blood was collected before intubation and 1, 2, 3 and 7 days after intubation to detect arterial blood gas in the ICU.

If the adverse events of esketamine appear during the study, patients or authorized client withdraw from the study actively, or drugs that seriously affect systemic inflammation and immune function (such as non-steroidal anti-inflammatory drugs, immunosuppressants, immunoenhancers, high doses of hormones (more than 10mg prednisolone per day or equivalent dose of other hormones, etc.) were used in clinical treatment, the study will be terminated. In this study, adverse reactions were evaluated daily after inclusion.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Critically Ill Patients
Intervention  ICMJE
  • Drug: Esketamine Hydrochloride 28 Mg in 0.2 mL NASAL SOLUTION [Spravato]
    Esketamine at 0.5-1.0 mg/kg BW and rocuronium bromide at 0.6 mg/kg BW was given intravenously for induction intubation. After the intubation was completed, esketamine was continuously pumped at 0.3-1.5 mg/kg/h to maintain sedation.
    Other Name: (S)-ketamine
  • Drug: midazolam, fentanyl
    Midazolam at 0.1mg/kg BW, fentanyl at 1ug/kg BW, rocuronium bromide at 0.6mg/kg BW was given intravenously for induction intubation; After the intubation was completed, sufentanil at 0.1 μg/kg/h was administered for analgesia, and remazolam tosylate at an initial dose of 0.075 mg/kg/h was administered for sedation, and the dose of remazolam tosylate was adjusted according to the RASS score.
Study Arms  ICMJE
  • Experimental: Esketamine intubation group
    Esketamine at 0.5-1.0 mg/kg BW and rocuronium bromide at 0.6 mg/kg BW was given intravenously for induction intubation. After the intubation was completed, esketamine was continuously pumped at 0.3-1.5 mg/kg/h to maintain sedation. The Richmond Agitation Sedation Scale (RASS) was used to assess the sedation of patients every 1 hour and maintains a RASS score of -2 to 0.
    Intervention: Drug: Esketamine Hydrochloride 28 Mg in 0.2 mL NASAL SOLUTION [Spravato]
  • Placebo Comparator: Conventional intubation group
    Midazolam at 0.1mg/kg BW, fentanyl at 1ug/kg BW, rocuronium bromide at 0.6mg/kg BW was given intravenously for induction intubation; After the intubation was completed, sufentanil at 0.1 μg/kg/h was administered for analgesia, and remazolam tosylate at an initial dose of 0.075 mg/kg/h was administered for sedation, and the dose of remazolam tosylate was adjusted according to the RASS score. The RASS score was assessed every 1 h and maintained at -2 to 0.
    Intervention: Drug: midazolam, fentanyl
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 17, 2022)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2024
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients aged 18-80 years old without restriction of gender, race, religion, creed or nationality;
  • No sedative drugs with elimination half-life were used before inclusion in the study;
  • Patients and/or their family members know and agree to participate in the trial.

Exclusion Criteria:

  • Allergic to esketamine or midazolam;
  • Patients with cardiac arrest during intubation;
  • Patients with suspected increased intracranial pressure;
  • bradycardia (heart rate below 50 beats/min) or atrioventricular block;
  • Untreated or undertreated patients with hyperthyroidism;
  • Diseases that may affect immune-related indicators, including autoimmune diseases (rheumatoid arthritis and systemic lupus erythematosus, etc.), and malignant hematological tumours (leukaemia and lymphoma, etc.);
  • Received radiotherapy or chemotherapy or received immunosuppressive drug treatment within the past 30 days, or received more than 10 mg of prednisolone per day (or other hormones at the same dose) continuous treatment;
  • History of solid organ or bone marrow transplantation;
  • Chronic nephrosis;
  • Severe chronic liver disease (child-Pugh: Grade C);
  • alcohol or opioid dependence, mental illness, or severe cognitive impairment;
  • Pregnant or breastfeeding;
  • Patients and/or their family members refuse to participate in the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jiancheng Zhang, MD, PhD +8613554105815 zhjcheng1@126.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05464979
Other Study ID Numbers  ICMJE ZJC202203
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: After publication, the data supporting the findings of this study can be provided by the corresponding author upon reasonable request. Participant data without names and identifiers can be provided by the corresponding author and the Wuhan Union Hospital after approval. The research team will provide an email address for communication purposes once approval is obtained regarding sharing the data with others. The proposal with detailed description of the study objectives and statistical analysis plan will be needed for evaluation of the purpose for the data request. Additional materials may also be required during the process of evaluation.
Supporting Materials: Study Protocol
Time Frame: Six months after publication.
Access Criteria: Upon reasonable request.
Current Responsible Party Wuhan Union Hospital, China
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Wuhan Union Hospital, China
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jiancheng Zhang, MD, PhD Wuhan Union Hospital, China
PRS Account Wuhan Union Hospital, China
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP