Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients

Analgesia Clinical Trial

— SEEDS  

Official title:

Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients in the ICU: a Prospective, Randomized, Single-center Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05466708
• Other study ID #: 2021120884Esketamine
• Status: Recruiting
• Phase: Phase 4
• Start date: August 11, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: May 2024
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Zuo Xiangrong
• Phone: +86 13913979197
• Email: zuoxiangrong[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective, randomized controlled study was conducted to compare the effects of esketamine combined with dexmedetomidine in the sedation and analgesia treatment of mechanically ventilated patients in the ICU on the time to awaken, time to extubation, time to mechanical ventilation, time in the ICU, and on delirium.

Description:

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with rapid onset of action, easy to wake up, no accumulation in the body, little inhibition of respiration, sedative, hypnotic and anxiolytic effects, and also has a certain analgesic effect.Clinical studies have shown that the use of dexmedetomidine for sedation in ICU patients is beneficial in reducing the duration of mechanical ventilation and the incidence of delirium is low, but the sedative effect of dexmedetomidine is relatively weak, and has the side effects of slowing down heart rate and lowering blood pressure, so its clinical application is limited.Esketamine is an isomer of ketamine, its effect is stronger than ketamine, and glutamate N-methyl D-aspartate (NMDA) receptor binding, play a sedative, hypnotic, analgesic effect, rapid onset, strong effect, and small respiratory inhibition, bronchodilator effect, the disadvantage is that there is a vasoconstrictor effect can cause increased blood pressure, increased heart rate. The combination of esketamine and dexmedetomidine can provide effective sedation and analgesia with the advantages of maintaining hemodynamic stability, maintaining stable spontaneous breathing and reducing psychiatric symptoms, and has been successfully used in clinical operations such as endoscopy, pediatric anesthesia and outpatient tooth extraction. The effectiveness and safety of esketamine in combination with dexmedetomidine for the sedation of mechanically ventilated patients in the ICU has not been evaluated. In this study, a prospective, randomized, controlled, single-center study was conducted to evaluate the efficacy and safety of esketamine in combination with dexmedetomidine for the sedation of mechanically ventilated patients in the ICU.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Mechanically ventilated with oral endotracheal intubation in the ICU;
• Patients aged >18 years and <70 years;
• Patients with expected mechanical ventilation time >24 hours.

Exclusion Criteria:

• Known or suspected allergy to esketamine, dexmedetomidine, remifentanil, or propofol;
• Pregnancy or lactation periods;
• Obesity defined as Body Mass Index >35kg/m2;
• Extreme hemodynamic or respiratory instability due to severe burn or trauma (defined as Injury Severity Score =25);
• Heavy drinking defined by WHO as drinking at least 60g of pure alcohol every day for men and at least 40g for women;
• Terminally ill patients near death, such as patients with extensively metastatic tumor or refractory shock;
• Long-term exposure to sedatives, opioid analgesics or antianxiety drugs;
• Severe central nervous system disease such as cerebrovascular accidents, status epilepsy, or coma;
• Acute or chronic severe liver disease (Child-Pugh class C or history of liver transplant);
• Acute or chronic renal insufficiency needing dialysis;
• Patients or authorized surrogates refuse to provide informed consents;
• Mechanically ventilated for more than 24 hours prior to enrollment (not including the time on ventilators in the operation room).

Related Conditions & MeSH terms

• Analgesia
• Dexmedetomidine
• Intensive Care Units
• Ketamine
• Mechanical Ventilation

Intervention

Drug:
• Esketamine combined with dexmedetomidine
Esketamine, injection, 50mg/ bottle, source: hospital pharmacy, production unit: Jiangsu Hengrui Pharmaceutical Co., LTD., validity: 2 years, storage condition: airtight shading, room temperature. Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature.
• Dexmedetomidine
Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature.

Locations

Country	Name	City	State
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of mechanical ventilation	Duration of mechanical ventilation after endotracheal intubation	Usually within 14 days
Secondary	Time to extubation	Daily offline screening, SBT test if eligible, and extubation if SBT is successful	Usually within 14 days
Secondary	Duration of ICU stay	Length of stay in ICU	Usually within 28 days
Secondary	28-day mortality rate	Mortality of patients within 28 days from the time of tracheal intubation	Within 28 days
Secondary	Recovery time	From the stop of sedatives to awakening	Within 14 days
Secondary	Dose of Propofol	Total dose of rescue propofol	Within 14 days
Secondary	Occurrence of delirium	The proportion of participants who have at least one positive CAM-ICU	Within 14 days
Secondary	Adverse reactions	Adverse reactions that patients experience with the medication, such as hypertension, hypotension, rapid heart rate, slow heart rate	Within 28 days