RemImazolam Besylate for ICU-sedation in Patients With Mechanical Ventilation After Oral and Maxillofacial Surgery

RemImazolam Besylate for ICU-sedation in Patients With Mechanical Ventilation After Oral and Maxillofacial Surgery: Multicenter, Randomized, Non-inferiority Clinical Study

Remimazolam besylate, as a new benzodiazepine drug, showing rapid clearance and moderate distribution of pharmacokinetic changes. The study will further explore the safety and effectiveness of remimazolam besylate n the sedation of mechanically ventilated patients after oral and maxillofacial surgery in the ICU.

Study Overview

• Status: Recruiting
• Conditions: Sedation; ICU; Remimazolam Besylate
• Intervention / Treatment: Drug: Remimazolam Besylate; Drug: Propofol; Drug: Midazolam

Detailed Description

Remimazolam besylate is a new type of ultra-short-acting benzodiazepine, showing rapid clearance and moderate distribution of pharmacokinetic changes. Remimazolam has been widely studied for programmed sedation in endoscopic procedures such as gastroenteroscopy and bronchoscopy. Remimazolam, as a short-acting sedative agent that is not metabolized by liver or kidney, can achieve rapid and reversible sedation and has the potential to shorten the duration of mechanical ventilation.

In the oral and maxillofacial surgical treatment, the use of microvascular free tissue transfer for reconstruction is one of the common operations. In order to avoid mechanical damage to the transplanted reconstructed tissue due to spontaneous movement, patients undergoing major head and neck reconstruction surgery are considered to require postoperative deep sedation for a certain period of time (RASS score required -4/-5 points). Deep sedation may cause hypotension and lead to reduced flap perfusion pressure, increasing the risk of hypoperfusion and flap necrosis, thus requiring close postoperative monitoring in the ICU.

Therefore, there is an urgent need for a sedative drug that can achieve rapid and sufficient sedation, does not inhibit breathing and can reduce the amount of patients or rapid recovery after drug withdrawal without increasing delirium. Based on the deficiencies of currently used sedatives and the potential advantages of remimazolam, we hypothesize that remimazolam can shorten the extubation time and lower the adverse reaction rate in patients with oropharyngeal cancer after mechanical ventilation sedation.

This clinical study was a randomized, multi-center, parallel-controlled, non-inferior clinical study. After signing the informed consent, participants meeting the inclusion/exclusion criteria will be randomly assigned to the treatment group (ramazolam besylate) and the control group (propofol, midazolam) in a ratio of 1:1:1, with a total of 285 participants recruited.

• Study Type: Interventional
• Enrollment (Estimated): 285
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hongbin Hu, doctor; Phone Number: +8613922483752; Email: hobewoos@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Southern Medical University Nanfang Hospital
      • Contact: Hongbin Hu, doctor; Phone Number: +8613922483752; Email: hobewoos@163.com
    • Shenzhen, Guangdong, China, 518036
      • Not yet recruiting
      • Peking University Shenzhen Hospital
      • Contact: Lei Huang, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years old;
• After undergoing oral and maxillofacial surgery, it is expected that a ventilator will be needed to assist with breathing;
• mechanical ventilation patients with expected ICU stay time <72h;
• People who need immediate sedative treatment;
• Obtain informed consent from subject or legal representative;

Exclusion Criteria:

• Pregnancy；
• Can not get RASS score from patients;
• Allergy to drugs;
• Proven acute and severe intracranial or spinal nerve disease due to vascular, infection, intracranial dilation, or injury;
• Uncompensated acute circulatory failure at randomization (severe hypotension with MAP<50 mmHg despite adequate fluid resuscitation and vasopressor therapy);
• Severe bradycardia (heart rate <50 beats/min) or degree II-III heart block (unless a pacemaker is installed);
• A history of long-term use of benzodiazepines or opioids;
• Subjects receiving sedation for indications other than to tolerate ventilators (e.g., epilepsy);
• Continuous sedation is unlikely to be required during mechanical ventilation (e.g. Guillain-Barre syndrome);
• Patients determined by the clinician to be unlikely to be removed from mechanical ventilation, such as diseases/injuries that primarily affect respirator neuromuscular function and conditions that clearly require long-term ventilation support (such as high spinal cord injury);
• Participation in any other interventional study (any study that assigns subjects to different treatment groups and/or performs unconventional diagnostic or monitoring procedures).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam besylate; Remimazolam besylate is a new ultra-short-acting benzodiazepine drug, which is a benzodiazepine central nervous system inhibitor. It can bind to central GABAA receptors and produce sedative effects in animal experiments. Currently, it is used in painless diagnosis and treatment sedation, colonoscopy sedation, general anesthesia, ICU sedation and local anesthesia sedation.	Drug: Remimazolam Besylate; NS 50ML + Remimazolam besylate(50mg , 2mg:2ml), IV-Pump,maintenance dose 0.5-3mg/kg/h.
Active Comparator: propofol; Propofol, known chemically as 2, 6-diisopropyl phenol, is an organic compound with the chemical formula C12H18O and is a short-acting intravenous anesthetic used for the induction and maintenance of general anesthesia. It is often used in conjunction with epidural or spinal anesthesia, as well as with analgesics, muscle relaxants, and inhalation anesthetics.	Drug: Propofol; Propofol (50ml, 0.5g), IV-Pump, maintenance dose 0.3-4.0mg/kg/h.
Active Comparator: midazolam; Midazolam, an organic compound with the chemical formula C18H13ClFN3, is used clinically to treat insomnia and can also be used to induce sleep during surgery or diagnostic tests.	Drug: Midazolam; Midazolam (10mg,2ml), IV-Pump, maintenance dose 0.02-0.1mg/kg/h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extubation time	The time from discontinuation of sedation to withdrawal of tracheal catheter.	From date of using the intervention drugs until the date of extubation, up to 28 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recovery	The time from withdrawal of sedation to recovery.	From date of using the intervention drugs until the date of recovery, up to 28 days.
Drug onset time	The time from discontinuation of sedation to meeting the sedation score requirements (RASS score < -3).	From date of using the intervention drugs until the date of recovery, up to 28 days.
Time to reach the required sedation score	The proportion of time spent meeting sedation requirements (RASS score <-3) to total time spent on medication	From date of using the intervention drugs until the date of recovery, up to 28 days.
Mechanical ventilation time during ICU	Time from insertion to withdrawal of tracheal catheter.	From the time you enter ICU to the time you leave ICU.
Length of ICU stay and total hospital stay	Time from admission to ICU to leave ICU;The time from admission to discharge.	From hospitalization to discharge.
Adverse event rate	The proportion of cases with adverse events to the total number of cases for evaluation of adverse events.	From date of using the intervention drugs until the date of leaving hospital.

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Collaborators: Peking University Shenzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2022
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: November 2, 2022
• First Submitted That Met QC Criteria: November 3, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 7, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ICU; Sedation; Oral cancer; Remimazolam besylate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Propofol
• Other Study ID Numbers: NFEC-2021-341

Drug and device information, study documents

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