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

Sedation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05606315
• Other study ID #: NFEC-2021-341
• Status: Recruiting
• Phase: Phase 4
• Start date: March 16, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Nanfang Hospital, Southern Medical University
• Contact: Hongbin HU, doctor
• Phone: +8613922483752
• Email: hobewoos[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 285
• Est. completion date: December 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• ICU
• Sedation

Intervention

Drug:
• Remimazolam Besylate
NS 50ML + Remimazolam besylate(50mg , 2mg:2ml), IV-Pump,maintenance dose 0.5-3mg/kg/h.
• Propofol
Propofol (50ml, 0.5g), IV-Pump, maintenance dose 0.3-4.0mg/kg/h.
• Midazolam
Midazolam (10mg,2ml), IV-Pump, maintenance dose 0.02-0.1mg/kg/h.

Locations

Country	Name	City	State
China	Southern medical university Nanfang hospital	Guangzhou	Guangdong
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Nanfang Hospital, Southern Medical University	Peking University Shenzhen Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.