Clinical trial NCT06009991: The Dose Range of Remimazolam Besylate in Different Age Groups
Official title: The Investigation of the Dose Range of Remimazolam Besylate in Different Age Groups of Adults and Its Effects on Hemodynamics
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Remimazolam
Anesthesia
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Renmin Hospital of Wuhan University
name: Wuhan University
name: The General Hospital of Central Theater Command
name: Taihe Hospital
name: Yichang Central People's Hospital
name: Jingzhou Central Hospital
name: Beijing Shijitan Hospital, Capital Medical University
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: First Affiliated Hospital of Fujian Medical University
name: Tianjin Nankai Hospital
name: Sichuan Provincial People's Hospital
name: Shanxi Bethune Hospital
First posted: 2023-08-24
Enrollment: 1876
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, parallel, controlled clinical study of patients at different ages underwent elective non-cardiac surgery under general anesthesia. The aim of this study is to explore the dose range of remimazolam besylate for patients at different ages, to provide guidance for anesthesia induction and maintenance of remimazolam besylate. And to investigate the incidence of perioperative hypotension and postoperative related organ dysfunction in patients received total intravenous anesthesia with remimazolam besylate, compared with propofol.

Detailed description: Surgery is an effective method to treat surgical diseases, prolong survival time and improve the quality of life, but patients often face the risk of postoperative complications. In general surgery patients, complications occur in more than 30% of patients. Several observational studies have shown that the severity and duration of intraoperative hypotension are significantly related to the risk of postoperative adverse events such as myocardial injury, renal injury, stroke, delirium, prolonged hospitalization, and death.

Hypotension, defined as a systolic blood pressure of less than 90 mmHg, a diastolic blood pressure of less than 50 mmHg, or a 20% reduction in systolic blood pressure from baseline, is common during anesthesia and surgery. More than a third of patients receiving propofol sedation experience intraoperative hypotension events, and their duration and degree are associated with harm during surgery.

Remimazolam is a new ultra-short-acting sedative drug developed in recent years, which has a similar structure to midazolam. However, compared with midazolam, remimazolam has the advantages of faster onset, faster recovery, and higher safety. Compared with propofol, remimazolam is noninferior in the success rate of sedation, while the incidence of adverse events such as hypotension is lower. At present, remimazolam has completed phase III clinical studies in many fields, such as colonoscopy, fiberoptic bronchoscopy, and general anesthesia induction and maintenance, which have shown its safety and effectiveness. However, there may be differences in hemodynamics and drug sensitivity among patients of different ages. Compared with young patients, elderly patients have a higher risk of hypotension after anesthesia induction. At present, there is a lack of clinical studies with large samples to clarify the recommended dose of remimazolam for anesthesia induction and maintenance in patients of all ages. The updated instructions for remimazolam besylate for injection on March 28, 2022 also mention that remimazolam besylate is used as a sedative drug for general anesthesia induction and maintenance, and the relevant dose reference is given. However, the safety and effectiveness of patients over 65 years have not been confirmed. The precise regulation of clinical use for patients of different ages and the optimization of drug dosage during anesthesia induction and maintenance are the basis for ensuring the safety of clinical medication at present., in order to maintain the stability of perioperative hemodynamics, and prevent or reduce the occurrence of adverse cardiovascular events.

This study aims to investigate the effect of remimazolam total intravenous anesthesia on intraoperative hemodynamics and the drug requirement for patients of different ages, with propofol as the control, and intraoperative hemodynamics as the main evaluation index, so as to provide evidence for clinical application of remimazolam for elderly patients in anesthesia induction and maintenance.

Eligibility criteria: Inclusion Criteria:

1. age above 45 years old;
2. American Society of Anesthesiologists grade Ⅰ-II;
3. patients undergoing tracheal intubation or laryngeal mask airway surgery under general anesthesia (intravenous anesthesia);
4. Informed consent: patients voluntarily participated in the trial and signed the informed consent form.

Exclusion Criteria:

1. patients with cardiac function grade 3 or above;
2. difficult to observe the pupil size of head or neck surgery patients;
3. patients with multimodal anesthesia such as nerve block or spinal anesthesia compounded;
4. patients known to be allergic to remimazolam besylate or benzodiazepines;
5. major vascular surgery and the type of surgery that directly affects hemodynamics;
6. patients with coagulation dysfunction, endocrine diseases or other hemodynamic conditions;
7. minor surgery (operation duration \<1 hour);
8. surgery lasting more than 4 hours;
9. emergency surgery;
10. patients with a history of drug or alcohol dependence;
11. Subjects deemed unsuitable for the study by the investigator.

Primary outcomes:
measure: Occurrence of intraoperative hypotension
timeFrame: Operation 1 day
Secondary outcomes:
measure: Intraoperative dosage of vasoactive drugs
timeFrame: Operation 1 day
measure: Anesthesia recovery
timeFrame: Operation 1 day
measure: Cognitive function assessment
timeFrame: Operation 1 day
measure: Major organ complications
timeFrame: Within 30 days after surgery
measure: Hospital stay of patients
timeFrame: With 30 days after surgery
measure: 30-day mortality after surgery
timeFrame: 30-day after surgery
Other outcomes:
Locations:
city: Wuhan
country: China
facility: ongji Hospital, Tongji Medical College, Huazhong Science and Technology University
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Ailin Luo
role: PRINCIPAL_INVESTIGATOR
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