Efficacy and Safety of Remifentanil for Mechanically Ventilated Patients in Intensive Care Unit

Southeast University, China

Status and phase: Enrolling; Phase 3

Conditions: Analgesia

Treatments: Drug: Fentanyl; Drug: Remifentanil

Study type: Interventional

Funder types: Other

Identifiers

NCT05641909

ZDRFF

Details and patient eligibility

About

Remifentanil has been approved by the FDA for continuation as an analgesic into the immediate postoperative period in adult patients under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting. However, National Medical Products Administration(NMPA) did not approve this indication. Therefore, the purpose of this study is to confirm the efficacy and safety of remifentanil in the analgesic therapy of critical ill patients in China.

Full description

The study was conducted in accordance with good clinical practice and with the guidelines set out in the Declaration of Helsinki. After approval from local and national ethics committees, patients from 18 centres in China were recruited. All patients were randomized, in a double-blind manner, to receive either a remifentanil-propofol regimen or a fentanyl-propofol regimen for analgesia and sedation in the ICU. The aim of the study was to achieve optimal sedation and patient comfort by maintaining an optimal Critical Care Pain Observation Tool (CPOT) score of 2, without clinically significant pain, until the start of the extubation process or for 72 hours, whichever occurred first. CPOT scoring criteria: Facial expressions(Relaxed, neutral=0; Tense=1; Grimacing=2); Body movements(Absence of movements or normal position=0; Protection=1; Restlessness/Agitation=2); Muscle tension(Relaxed=0; Tense, rigid=1; Very tense or rigid=2); Compliance with the ventilator or Vocalization(Tolerating ventilator or movement/Talking in normal tone or no sound=0; Coughing but tolerating/Sighing, moaning=1; Fighting ventilator/Crying out, sobbing=2).

Enrollment: 138 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Intubated in the past 24 hours with invasive mechanical ventilation
• Expected to continue mechanical ventilation for more than 48 hours
• Informed consent/assent was obtained from all patients or their representatives

Exclusion criteria

• Patients with a history of allergy to opioids, benzodiazepines, propofol, or alcohol/drug abuse were excluded from the study
• Patients who are known or suspected to be allergic to the study drug
• Patients whose expected survival time is less than 48h
• Patients receiving deep sedation (RASS≥-4)
• Patients using neuromuscular blocking agent
• Patients who cannot be assessed by RASS
• Patients with myasthenia gravis
• patients with bronchial asthma
• patients with abdominal compartment syndrome
• Patients who need surgery or tracheotomy during the study drug treatment period
• Women during pregnancy and lactation
• Patients who have used short-acting non-steroidal anti-inflammatory drugs within 6 hours
• Patients who have used long-acting non-steroidal anti-inflammatory drugs within 12 hours
• Patients with a history of chronic pain for more than 3 months or who are receiving regular analgesia for more than 3 months
• Patients who have used monoamine oxidase inhibitors within two weeks
• Patients who participate in any clinical trials as subjects within 1 month
• Patients with a history of drug abuse, drug abuse, alcohol abuse* and long-term use of psychotropic drugs within 2 years Alcoholism: Drinking more than 14 times/week (1 time=150ml wine or 360ml beer or 45ml spirits)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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138 participants in 2 patient groups

Remifentanil

Experimental group

Description:

Remifentanil analgesia combined with propofol sedation. Treatment was started in patients with an CPOT score of 2 or greater after completion of baseline assessments. All patients received an initial infusion of blinded opioid (placebo bolus dose(6ml) + 6ug/kg per hour infusion at 6 ml/hour). Optimal analgesia (CPOT score ≤2) was then targeted by titrating the infusion in 1.5 ml/hour increments (placebo bolus dose + 1.5ug/kg per hour rate increase). Only when the opioid infusion rate had reached the 'propofol trigger dose' (12ml/h; 12ug/ kg per hour) was propofol to be administered as an initial bolus dose of up to 0.5 mg/kg and an infusion of 0.5mg/kg per hour, and titrated in 25% increments (0.25mg/kg bolus dose + 0.125mg/kg per hour rate increase to treat agitation.

Treatment:

Drug: Remifentanil

Fentanyl

Active Comparator group

Description:

Fentanyl analgesia combined with propofol sedation. Treatment was started in patients with an CPOT score of 2 or greater after completion of baseline assessments. All patients received an initial infusion of blinded opioid (1ug/kg bolus(6ml) + 1ug/kg per hour infusion at 6ml/hour). Optimal analgesia (CPOT score ≤2) was then targeted by titrating the infusion in 1.5 ml/hour increments (1ug/kg bolus dose + 0.25ug/kg per hour rate increase). Only when the opioid infusion rate had reached the 'propofol trigger dose' (12ml/h; 2ug/kg per hour) was propofol to be administered as an initial bolus dose of up to 0.5 mg/kg and an infusion of 0.5mg/kg per hour, and titrated in 25% increments (0.25mg/kg bolus dose + 0.125mg/kg per hour rate increase to treat agitation.

Treatment:

Drug: Fentanyl