Clinical trial NCT05003570: Efficacy and Safety of Remifentanil for Mechanically Ventilated Patients in ICU
Official title: Efficacy and Safety of Remifentanil for Mechanically Ventilated Patients in Intensive Care: Multicenter, Random, Double-blind, Parallel, Positive Control Clinical Trials
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Analgesia
Keywords: analgesia
analgesia based sedation
critical care
fentanyl
propofol
remifentanil
sedation
mechanical ventilation
efficacy
safety
Lead sponsor: Southeast University, China
Sponsor class: OTHER
First posted: 2021-08-12
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 17 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).

Eligibility criteria: Inclusion Criteria:

* Invasive mechanical ventilation with endotracheal intubation
* Expected to continue mechanical ventilation for more than 12 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)

Primary outcomes:
measure: analgesia success rate(the proportion of subjects with successful analgesia to the number of subjects in each group)
timeFrame: From study drug administration to actual extubation , up to 72 hours
Secondary outcomes:
measure: During the study drug administration period, the subjects are in the proportion of optimal time(CPOT score≤2)
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: The number of times the remedial sedative drug propofol was used
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: The proportion of subjects using the salvage sedative drug propofol
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: The dosage of the remedial sedative drug propofol
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: Wearing time from mechanical ventilation
timeFrame: From study drug administration to wearing from mechanical ventilation, up to 72 hours
measure: Extubation time
timeFrame: From the start of the extubation process until actual extubation , up to 72 hours
measure: The success rate of wearing mechanical ventilator
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: Duration of study drug use in ICU
timeFrame: From study drug administration to the time discharge ICU , up to 72 hours
measure: The proportion of subjects discharging the ICU
timeFrame: From study drug administration to the time discharge ICU, up to 24 weeks
measure: ICU mortality
timeFrame: From study drug administration to the time discharge ICU, up to 24 weeks
measure: Hospital mortality
timeFrame: From study drug administration to the time discharge hospital, up to 24 weeks
measure: Length of ICU stay
timeFrame: From administration to discharge ICU, up to 24 weeks
measure: Length of hospital stay
timeFrame: From administration to discharge hospital, up to 24 weeks
measure: The incidence of study drug-related Lower blood pressure
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: The incidence of study drug-related slow heart rate
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: The incidence of study drug-related respiratory depression
timeFrame: From study drug administration to actual extubation , up to 72 hours
measure: Analysis of the cost-effectiveness between remifentanil and fentanyl
timeFrame: From study drug administration to actual extubation , up to 72 hours
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Enshi
country: China
facility: Enshi Tujia and Miao Autonomous Prefecture Central Hospital
state: Hubei
city: Yichang
country: China
facility: Yichang Central People's Hospital
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Zhong-Da Hospital, Southeast University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University
name: Yang Yi, MD
role: STUDY_CHAIR
References: