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

Nanfang Hospital, Southern Medical University

Status and phase: Enrolling; Phase 4

Conditions: Remimazolam Besylate; ICU; Sedation

Treatments: Drug: Propofol; Drug: Midazolam; Drug: Remimazolam Besylate

Study type: Interventional

Funder types: Other

Identifiers

NCT05606315

NFEC-2021-341

Details and patient eligibility

About

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.

Full 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.

Enrollment: 285 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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285 participants in 3 patient groups

Remimazolam besylate

Experimental group

Description:

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.

Treatment:

Drug: Remimazolam Besylate

propofol

Active Comparator group

Description:

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.

Treatment:

Drug: Propofol

midazolam

Active Comparator group

Description:

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.

Treatment:

Drug: Midazolam