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

Analgesia Clinical Trial

Official title:

Efficacy and Safety of Remifentanil for Mechanically Ventilated Patients in Intensive Care: Multicenter, Random, Double-blind, Parallel, Positive Control Clinical Trials

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05641909
• Other study ID #: ZDRFF
• Status: Recruiting
• Phase: Phase 3
• Start date: August 1, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: November 2022
• Source: Southeast University, China
• Contact: Sonqiao Liu, MD
• Phone: +86-25-83262552
• Email: liusongqiao[@]ymail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: December 31, 2022
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Analgesia

Intervention

Drug:
• Remifentanil
Remifentanil
• Fentanyl
Dosage forms and strengths: 50 mcg/mL Fentanyl base/10 mL ampules. Manufacturer: Yichang Humanwell Pharmaceutical Co.,Ltd

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Enshi Tujia and Miao Autonomous Prefecture Central Hospital	Enshi	Hubei
China	Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Anhui Provincial People's Hospital	Hefei	Anhui
China	Nanjing Zhong-Da Hospital, Southeast University	Nanjing
China	Qingyuan People's Hospital	Qingyuan	Guangdong
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin First Central Hospital	Tianjin	Tianjin
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Northern Jiangsu People's Hospital	Yangzhou	Jiangsu
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	Affiliated Hospital of Zunyi Medical University	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
Southeast University, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	analgesia success rate(the proportion of subjects with successful analgesia to the number of subjects in each group)	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).	From study drug administration to actual extubation , up to 72 hours
Secondary	During the study drug administration period, the subjects are in the proportion of optimal time(CPOT score=2)	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).	From study drug administration to actual extubation , up to 72 hours
Secondary	The number of times the remedial sedative drug propofol was used	Use the total times of propofol	From study drug administration to actual extubation , up to 72 hours
Secondary	The proportion of subjects using the salvage sedative drug propofol	The proportion of subjects who using the salvage sedative drug propofol to the total subjects.	From study drug administration to actual extubation , up to 72 hours
Secondary	The dosage of the remedial sedative drug propofol	Use the total dose of propofol	From study drug administration to actual extubation , up to 72 hours
Secondary	Wearing time from mechanical ventilation	Wearing time criteria: The primary disease is improved, and there is no new disease; no use of vasopressors or continuous application of sedative drugs; cough reflex during sputum suction; PEEP=5cmH2O; PaO2/FiO2=200mmHg; Minute ventilation less than 15L/min; 2-minute spontaneous breathing test and passed.	From study drug administration to wearing from mechanical ventilation, up to 72 hours
Secondary	Extubation time	The start of the extubation process until actual extubation	From the start of the extubation process until actual extubation , up to 72 hours
Secondary	The success rate of wearing mechanical ventilator	The proportion of subjects who successfully wearing from mechanical ventilator to the total subjects.	From study drug administration to actual extubation , up to 72 hours
Secondary	Duration of study drug use in ICU	The time from the start of the study drug administration to the time discharge ICU.	Through study completion, an average of 1 month
Secondary	The proportion of subjects discharging the ICU	The proportion of subjects who discharge ICU to the total subjects.	Through study completion, an average of 1 month
Secondary	ICU mortality	The proportion of subjects who died during ICU admission to the total subjects.	Through study completion, an average of 1 month
Secondary	Hospital mortality	The proportion of subjects who died during hospital admission to the total subjects.	Through study completion, an average of 1 month
Secondary	Length of ICU stay	The number of days the subject stayed in the ICU.	Through study completion, an average of 1 month
Secondary	Length of hospital stay	The number of days the subject stayed in the hospital.	Through study completion, an average of 1 month
Secondary	The incidence of study drug-related Lower blood pressure	Lower blood pressure: mean arterial pressure (MAP) drops more than 25% from the baseline level or requires additional vasopressors.	From study drug administration to actual extubation , up to 72 hours
Secondary	The incidence of study drug-related slow heart rate	Slow heart rate: heart rate less than 40bpm for less than 1 minute or heart rate less than 60 bpm for more than 1 minute.	From study drug administration to actual extubation , up to 72 hours
Secondary	The incidence of study drug-related respiratory depression	Respiratory depression: respiratory rate less than 10 bpm or oxygen saturation by pulse oximetry less than 90%	From study drug administration to actual extubation , up to 72 hours
Secondary	Analysis of the cost-effectiveness between remifentanil and fentanyl	Analyze the best analgesic plan based on the results of the best analgesic effect	From study drug administration to actual extubation , up to 72 hours