Efficacy and Safety of Remifentanil for Mechanically Ventilated Patients in Intensive Care: Multicenter, Random, Double-blind, Parallel, Positive Control Clinical Trials
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 138
- 试验地点
- 18
- 主要终点
- analgesia success rate(the proportion of subjects with successful analgesia to the number of subjects in each group)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Remifentanil
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.
干预措施: Remifentanil (Drug)
Fentanyl
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.
干预措施: Fentanyl (Drug)
结局指标
主要结局
analgesia success rate(the proportion of subjects with successful analgesia to the number of subjects in each group)
时间窗: From study drug administration to actual extubation , up to 72 hours
Analgesia success is defined as: 1. No salvage analgesics were used during the administration of the study drug; 2 During the administration of the study drug, the time for the analgesia score of subjects to reach the standard (CPOT score ≤ 2) was greater than 70%. 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).
次要结局
- The proportion of subjects using the salvage sedative drug propofol(From study drug administration to actual extubation , up to 72 hours)
- The success rate of wearing mechanical ventilator(From study drug administration to actual extubation , up to 72 hours)
- The proportion of subjects discharging the ICU(Through study completion, an average of 1 month)
- During the study drug administration period, the subjects are in the proportion of optimal time(CPOT score≤2)(From study drug administration to actual extubation , up to 72 hours)
- The dosage of the remedial sedative drug propofol(From study drug administration to actual extubation , up to 72 hours)
- Length of ICU stay(Through study completion, an average of 1 month)
- The incidence of study drug-related Lower blood pressure(From study drug administration to actual extubation , up to 72 hours)
- The number of times the remedial sedative drug propofol was used(From study drug administration to actual extubation , up to 72 hours)
- Extubation time(From the start of the extubation process until actual extubation , up to 72 hours)
- The incidence of study drug-related slow heart rate(From study drug administration to actual extubation , up to 72 hours)
- The incidence of study drug-related respiratory depression(From study drug administration to actual extubation , up to 72 hours)
- Analysis of the cost-effectiveness between remifentanil and fentanyl(From study drug administration to actual extubation , up to 72 hours)
- Wearing time from mechanical ventilation(From study drug administration to wearing from mechanical ventilation, up to 72 hours)
- Duration of study drug use in ICU(Through study completion, an average of 1 month)
- ICU mortality(Through study completion, an average of 1 month)
- Hospital mortality(Through study completion, an average of 1 month)
- Length of hospital stay(Through study completion, an average of 1 month)
研究者
Songqiao Liu
MD. PhD.
Southeast University, China