The Efficacy and Safety of Esketamine in Elective Laparoscopic Surgery

A Multicenter, Randomized, Double-blind Clinical Trial to Evaluate the Efficacy and Safety of BT-KTM-I Versus Ketanest® S for General Anesthesia in Elective Laparoscopic Surgery

The objective is to evaluate the efficacy and safety of BT-KTM-I(Esketamine Hydrochloride Injection produced by Chengdu Brilliant Pharmaceutical Co., Ltd.) for general anesthesia, using the Originator drug Ketanest®S(Esketamine Hydrochloride Injection) as a positive control.

Study Overview

• Status: Not yet recruiting
• Conditions: Laparoscopy; Anesthesia, Intravenous
• Intervention / Treatment: Drug: BT-KTM-I; Drug: Ketanest®S

Detailed Description

This is a multicenter, randomized, double-blind, positive drug parallel controlled clinical trial, planned to include 358 subjects, including 179 in the experimental group and 179 in the control group. The entire study was divided into a screening period, surgery day, and follow-up observation period. The dosage for anesthesia induction period was 0.5mg/kg, and the dosage for anesthesia maintenance period was 0.5mg/kg/h. The experiment used vital signs, physical examination, laboratory examination, 12-lead electrocardiogram examination, and adverse events/serious adverse events for safety evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 358
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wen Ouyang, MD; Phone Number: 0731-88618151; Email: Ouyangwen133@vip.sina.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Xia Feng
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Jinan University
  • Guizhou
    • Guiyang, Guizhou, China
      • Guizhou Provincial People's Hospital
      • Contact: Fangxiang Zhang
    • Guiyang, Guizhou, China
      • The Affiliated Hospital of Guizhou Medical University
      • Contact: Xiaohua Zou
  • Hunan
    • Changsha, Hunan, China
      • The Third Xiangya Hospital of Central South University
      • Contact: Wen Ouyang, MD; Phone Number: 0731-88618151; Email: Ouyangwen133@vip.sina.com
    • Changsha, Hunan, China
      • Hunan Provincial Maternal and Child Health Care Hospital
      • Contact: Liang Chen
    • Hengyang, Hunan, China
      • The Second Hospital University of South China
      • Contact: Jie Luo
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
      • Contact: mengchang Yang
    • Chengdu, Sichuan, China
      • West China Second University Hospital, Sichuan University
      • Contact: Xuemei Lin
    • Chengdu, Sichuan, China
      • Pidu District People's Hospital, Chengdu
      • Contact: Junxiang Li
    • Neijiang, Sichuan, China
      • The Second People's Hospital of Neijiang
      • Contact: Chaoyu Li
    • Yibin, Sichuan, China
      • The Second People's Hospital of Yibin
      • Contact: Jinghua Ren

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age range from 18 to 60 years old (including threshold), regardless of gender;
2. Patients undergoing elective general anesthesia laparoscopic surgery (only tracheal intubation mechanical ventilation), 1 hour ≤ expected anesthesia time ≤ 2.5 hours;
3. The American Society of Anesthesiologists (ASA) score of Class I or II;
4. 18kg/m2<BMI<30kg/m2;
5. The subjects understand the purpose and procedure of this experiment, voluntarily participate in this experiment, and sign a written informed consent form.

Exclusion Criteria:

1. Patients with contraindications to general anesthesia, or those who have had previous anesthesia accidents;
2. Known intolerance or allergy to ketamine hydrochloride, esketamine hydrochloride, propofol, rocuronium bromide, opioids, neostigmine, atropine, belladonnae alkaloids;
3. Long-term (continuous or intermittent) use of benzodiazepines sleeping pills, opioid analgesics, or use of narcotic analgesics within 24 hours before randomization or use of narcotic drugs within 7 days;
4. Have a history of increased intraocular pressure (such as glaucoma) or puncture eye injury;
5. Patients with a history of asthma;
6. Patients with mental system diseases (schizophrenia, mania, insanity, etc.) or cognitive disorders;
7. Patients with a history of craniocerebral injury, possible presence of intracranial hypertension, cerebral aneurysm, cerebrovascular accident, and central nervous system disease;
8. Have a serious history of cardiovascular diseases (such as myocardial ischemia, heart failure and severe arrhythmia); Angina pectoris (unstable angina) caused by insufficient blood supply to the coronary arteries of the heart, or myocardial infarction occurring within the first 6 months before screening;
9. Hypertensive patients with systolic blood pressure still ≥ 140mmHg and/or diastolic blood pressure still ≥ 90mmHg after treatment with antihypertensive drugs;
10. Diabetic patients whose blood glucose was not satisfactorily controlled (fasting blood glucose ≥11.1mmol/L during the screening period);
11. Severe lipid metabolism abnormalities (such as triglycerides>5mmol/L, diabetic hyperlipidemia, familial hypercholesterolemia, lipoid nephropathy, acute pancreatitis with hyperlipidemia, etc.);
12. Have a history of hyperthyroidism;
13. Have a history of drug use within 2 years before screening;
14. Individuals with a history of alcohol abuse within 2 years before screening. alcoholism is defined as drinking more than 14 units of alcohol per week (1 unit =360mL beer or 45mL spirits with 40% alcohol or 150mL wine) or acute alcoholism or alcohol dependence;
15. Participants in any clinical trial (defined as receiving the experimental drug or placebo) within 3 months prior to screening;
16. Patients with respiratory management difficulties as determined by the investigators (modified Markov score level Ⅳ);
17. Abnormal coagulation function (PT or PT-INR ≥ 1.5×ULN, APTT ≥ 1.5×ULN), or with bleeding tendency (such as active digestive ulcer) or undergoing thrombolytic or anticoagulant treatment;
18. Anemia or thrombocytopenia (PLT≤80×109/L, HGB≤90g/L);
19. Abnormal liver function [ALT and (or) AST≥1.5×ULN, TBIL≥1.5×ULN];
20. Abnormal renal function (BUN≥1.5×ULN; Cr≥1.2×ULN)
21. Pregnant or lactating women; Women or men with fertility are unwilling to use contraception between the screening period and the end of the trial;
22. Subjects who are deemed by the investigators to have any other unfavorable factors for participating in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BT-KTM-I; Patients received 0.5mg/kg BT-KTM-I during anesthesia induction period. Patients received 0.5mg/kg/h BT-KTM-I during anesthesia maintenance period.	Drug: BT-KTM-I; The dosage for anesthesia induction period was 0.5mg/kg, and the dosage for anesthesia maintenance period was 0.5mg/kg/h.; Other Names: Esketamine
Active Comparator: Ketanest®S; Patients received 0.5mg/kg Ketanest®S during anesthesia induction period. Patients received 0.5mg/kg/h Ketanest®S during anesthesia maintenance period.	Drug: Ketanest®S; The dosage for anesthesia induction period was 0.5mg/kg, and the dosage for anesthesia maintenance period was 0.5mg/kg/h.; Other Names: Esketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The awakening time from anesthesia	The time from discontinuing the use of anesthetics (propofol) to subjects waking up immediately after surgery (following instructions to open their eyes)

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse reactions in the mental system	Within 60 minutes after the subject wakes up

Collaborators and Investigators

• Sponsor: Chengdu Brilliant Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Wen Ouyang, MD, The Third Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: October 15, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 15, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: BT-KTM-I-III-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No