The Dose Range of Remimazolam Besylate in Different Age Groups

Anesthesia Clinical Trial

Official title:

The Investigation of the Dose Range of Remimazolam Besylate in Different Age Groups of Adults and Its Effects on Hemodynamics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06009991
• Other study ID #: TongjiHospital-Anes QQ02
• Status: Recruiting
• Phase: N/A
• Start date: July 17, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2023
• Source: Tongji Hospital
• Contact: Qiaoqiao Xu
• Phone: +8618771006963
• Email: qiaoqiaoxu[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1876
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

1. age above 45 years old;

2. American Society of Anesthesiologists grade ?-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.

Related Conditions & MeSH terms

• Anesthesia
• Remimazolam

Intervention

Drug:
• Remimazolam besylate
Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need). Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).
• Propofol
Age 45-64: Propofol 3.0µg/ml TCI for anesthesia induction and 2.5-3.0µg/ml TCI for maintenance. Age over 65: Propofol 1.5-2.5µg/ml TCI for anesthesia induction and 1.5-2.5µg/ml TCI for maintenance

Locations

Country	Name	City	State
China	ongji Hospital, Tongji Medical College, Huazhong Science and Technology University	Wuhan	Hubei

Sponsors (13)

Lead Sponsor

Collaborator

Tongji Hospital

Beijing Shijitan Hospital, Capital Medical University, First Affiliated Hospital of Fujian Medical University, Jingzhou Central Hospital, Renmin Hospital of Wuhan University, Shanxi Bethune Hospital, Sichuan Provincial People's Hospital, Taihe Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The General Hospital of Central Theater Command, Tianjin Nankai Hospital, Wuhan University, Yichang Central People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (18)

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Babazade R, Yilmaz HO, Zimmerman NM, Stocchi L, Gorgun E, Kessler H, Sessler DI, Kurz A, Turan A. Association Between Intraoperative Low Blood Pressure and Development of Surgical Site Infection After Colorectal Surgery: A Retrospective Cohort Study. Ann — View Citation

Chen B, Pang QY, An R, Liu HL. A systematic review of risk factors for postinduction hypotension in surgical patients undergoing general anesthesia. Eur Rev Med Pharmacol Sci. 2021 Nov;25(22):7044-7050. doi: 10.26355/eurrev_202111_27255. — View Citation

Chen SH, Yuan TM, Zhang J, Bai H, Tian M, Pan CX, Bao HG, Jin XJ, Ji FH, Zhong TD, Wang Q, Lv JR, Wang S, Li YJ, Yu YH, Luo AL, Li XK, Min S, Li L, Zou XH, Huang YG. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non- — View Citation

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Doi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T. Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth. 2020 Aug;34(4):543-553. doi: 10 — View Citation

Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs S — View Citation

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Hallqvist L, Granath F, Fored M, Bell M. Intraoperative Hypotension and Myocardial Infarction Development Among High-Risk Patients Undergoing Noncardiac Surgery: A Nested Case-Control Study. Anesth Analg. 2021 Jul 1;133(1):6-15. doi: 10.1213/ANE.000000000 — View Citation

Mascha EJ, Yang D, Weiss S, Sessler DI. Intraoperative Mean Arterial Pressure Variability and 30-day Mortality in Patients Having Noncardiac Surgery. Anesthesiology. 2015 Jul;123(1):79-91. doi: 10.1097/ALN.0000000000000686. — View Citation

Mathis MR, Naik BI, Freundlich RE, Shanks AM, Heung M, Kim M, Burns ML, Colquhoun DA, Rangrass G, Janda A, Engoren MC, Saager L, Tremper KK, Kheterpal S, Aziz MF, Coffman T, Durieux ME, Levy WJ, Schonberger RB, Soto R, Wilczak J, Berman MF, Berris J, Bigg — View Citation

Pastis NJ, Yarmus LB, Schippers F, Ostroff R, Chen A, Akulian J, Wahidi M, Shojaee S, Tanner NT, Callahan SP, Feldman G, Lorch DG Jr, Ndukwu I, Pritchett MA, Silvestri GA; PAION Investigators. Safety and Efficacy of Remimazolam Compared With Placebo and M — View Citation

Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam — View Citation

Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A — View Citation

Saugel B, Reese PC, Sessler DI, Burfeindt C, Nicklas JY, Pinnschmidt HO, Reuter DA, Sudfeld S. Automated Ambulatory Blood Pressure Measurements and Intraoperative Hypotension in Patients Having Noncardiac Surgery with General Anesthesia: A Prospective Obs — View Citation

Sneyd JR, Absalom AR, Barends CRM, Jones JB. Hypotension during propofol sedation for colonoscopy: a retrospective exploratory analysis and meta-analysis. Br J Anaesth. 2022 Apr;128(4):610-622. doi: 10.1016/j.bja.2021.10.044. Epub 2021 Dec 13. — View Citation

Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018 Oct;121(4):706-721. doi: 10.1016/j.bja.2018.04.036. Epub 2018 Jun 20. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of intraoperative hypotension	Occurrence of intraoperative hypotension	Operation 1 day
Secondary	Intraoperative dosage of vasoactive drugs	Intraoperative dosage of vasoactive drugs	Operation 1 day
Secondary	Anesthesia recovery	Anesthesia recovery	Operation 1 day
Secondary	Cognitive function assessment	Cognitive function assessment in the anesthesia recovery room	Operation 1 day
Secondary	Major organ complications	The occurrence of major organ complications within 30 days after surgery	Within 30 days after surgery
Secondary	Hospital stay of patients	Hospital stay of patients	With 30 days after surgery
Secondary	30-day mortality after surgery	30-day mortality after surgery	30-day after surgery