Clinical trial NCT05606315: RemImazolam Besylate for ICU-sedation in Patients With Mechanical Ventilation After Oral and Maxillofacial Surgery
Official title: RemImazolam Besylate for ICU-sedation in Patients With Mechanical Ventilation After Oral and Maxillofacial Surgery: Multicenter, Randomized, Non-inferiority Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Remimazolam Besylate
Sedation
ICU
Keywords: Remimazolam besylate
Oral cancer
Sedation
ICU
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Peking University Shenzhen Hospital
First posted: 2022-11-04
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Extubation time
timeFrame: From date of using the intervention drugs until the date of extubation, up to 28 days.
Secondary outcomes:
measure: Time to recovery
timeFrame: From date of using the intervention drugs until the date of recovery, up to 28 days.
measure: Drug onset time
timeFrame: From date of using the intervention drugs until the date of recovery, up to 28 days.
measure: Time to reach the required sedation score
timeFrame: From date of using the intervention drugs until the date of recovery, up to 28 days.
measure: Mechanical ventilation time during ICU
timeFrame: From the time you enter ICU to the time you leave ICU.
measure: Length of ICU stay and total hospital stay
timeFrame: From hospitalization to discharge.
measure: Adverse event rate
timeFrame: From date of using the intervention drugs until the date of leaving hospital.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Southern medical university Nanfang hospital
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
Study officials:
References: