Efficacy and Safety of Remifentanil for Mechanically Ventilated Patients in ICU

August 9, 2022 updated by: Ling Liu, Southeast University, China

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
138

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230000
        • Recruiting
        • Anhui Provincial Hospital
        • Contact:
          • Pan Aijun, MD
          • Phone Number: +8613866668786
    • Beijing
      • Beijing, Beijing, China, 100000
        • Recruiting
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:
          • Zhou Jianxin, MD
          • Phone Number: +8613801183875
    • Chongqing
      • Chongqing, Chongqing, China, 404100
        • Recruiting
        • The First Affiliated Hospital of Chongqing Medical University
        • Contact:
          • Zhou Fachun, MD
          • Phone Number: +8618502388799
    • Guangdong
      • Qingyuan, Guangdong, China, 511500
        • Recruiting
        • Qingyuan People's Hospital
        • Contact:
          • Yang Jingwen, MD
          • Phone Number: +8613542498765
    • Guizhou
      • Guiyang, Guizhou, China, 550000
        • Recruiting
        • Affiliated Hospital of Guizhou Medical University
        • Contact:
          • Shen Feng, MD
          • Phone Number: +8613511999117
      • Zunyi, Guizhou, China, 563000
        • Recruiting
        • Affiliated Hospital of Zunyi Medical University
        • Contact:
          • Chen Tao, MD
          • Phone Number: +8615329112288
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Recruiting
        • The Fourth Hospital of Hebei Medical University
        • Contact:
          • Hu Zhenjie, MD
          • Phone Number: +8613933856908
    • Henan
      • Zhengzhou, Henan, China, 450000
        • Recruiting
        • Henan Provincial People's Hospital
        • Contact:
          • Qin Bingyu, MD
          • Phone Number: +8613633810677
      • Zhengzhou, Henan, China, 450000
        • Recruiting
        • First Affiliated Hospital of Zhengzhou University
        • Contact:
          • Sun Tongwen, MD
          • Phone Number: +8613838516916
    • Hubei
      • Enshi, Hubei, China, 445000
        • Recruiting
        • Enshi Tujia and Miao Autonomous Prefecture Central Hospital
        • Contact:
          • Li Dezhong, MD
          • Phone Number: +8615342885588
      • Yichang, Hubei, China, 443000
        • Recruiting
        • Yichang Central People's Hospital
        • Contact:
          • Gong Xun, MD
          • Phone Number: +8615872549520
    • Hunan
      • Changsha, Hunan, China, 410000
        • Recruiting
        • The Third XIANGYA Hospital of Central South University
        • Contact:
          • Yang Mingshi, MD
          • Phone Number: +8613973139006
      • Changsha, Hunan, China, 410000
        • Recruiting
        • Xiangya Hospital of Central South University
        • Contact:
          • Zhang Lina, MD
          • Phone Number: +8615874875763
    • Jiangsu
      • Nanjing, Jiangsu, China, 210009
        • Recruiting
        • Nanjing Zhong-Da Hospital, Southeast University
      • Yangzhou, Jiangsu, China, 225000
        • Recruiting
        • Northern Jiangsu People's Hospital
        • Contact:
          • Zheng Rui qiang, MD
          • Phone Number: +8613952721411
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Recruiting
        • Zhejiang Provincial People's Hospital
        • Contact:
          • Sun Renhua, MD
          • Phone Number: +8613505710366
      • Wenzhou, Zhejiang, China, 325000
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:
          • Pan Jingye, MD
          • Phone Number: +8613566289666

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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).
Drug: Remifentanil
Dosage forms and strengths: 3 mL Vial/1 mg lyophilized powder. Manufacturer: Yichang Humanwell Pharmaceutical Co.,Ltd
Other Names:
  • Remifentanil Hydrochloride for Injection
Active Comparator: 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).
Drug: Fentanyl
Dosage forms and strengths: 50 mcg/mL Fentanyl base/10 mL ampules. Manufacturer: Yichang Humanwell Pharmaceutical Co.,Ltd
Other Names:
  • Fentanyl Citrate Injection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
analgesia success rate(the proportion of subjects with successful analgesia to the number of subjects in each group)
Time Frame: 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).
From study drug administration to actual extubation , up to 72 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
During the study drug administration period, the subjects are in the proportion of optimal time(CPOT score≤2)
Time Frame: From study drug administration to actual extubation , up to 72 hours
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
The number of times the remedial sedative drug propofol was used
Time Frame: From study drug administration to actual extubation , up to 72 hours
Use the total times of propofol
From study drug administration to actual extubation , up to 72 hours
The proportion of subjects using the salvage sedative drug propofol
Time Frame: From study drug administration to actual extubation , up to 72 hours
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
The dosage of the remedial sedative drug propofol
Time Frame: From study drug administration to actual extubation , up to 72 hours
Use the total dose of propofol
From study drug administration to actual extubation , up to 72 hours
Extubation time
Time Frame: From the start of the extubation process until actual extubation , up to 72 hours
The start of the extubation process until actual extubation
From the start of the extubation process until actual extubation , up to 72 hours
The success rate of wearing mechanical ventilator
Time Frame: From study drug administration to actual extubation , up to 72 hours
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
Wearing time from mechanical ventilation
Time Frame: From study drug administration to wearing from mechanical ventilation, up to 72 hours
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<15L/min; 2-minute spontaneous breathing test and passed.
From study drug administration to wearing from mechanical ventilation, up to 72 hours
Duration of study drug use in ICU
Time Frame: From study drug administration to the time discharge ICU , up to 72 hours
The time from the start of the study drug administration to the time discharge ICU.
From study drug administration to the time discharge ICU , up to 72 hours
The proportion of subjects discharging the ICU
Time Frame: From study drug administration to the time discharge ICU, up to 24 weeks
The proportion of subjects who discharge ICU to the total subjects.
From study drug administration to the time discharge ICU, up to 24 weeks
ICU mortality
Time Frame: From study drug administration to the time discharge ICU, up to 24 weeks
The proportion of subjects who died during ICU admission to the total subjects.
From study drug administration to the time discharge ICU, up to 24 weeks
Hospital mortality
Time Frame: From study drug administration to the time discharge hospital, up to 24 weeks
The proportion of subjects who died during hospital admission to the total subjects.
From study drug administration to the time discharge hospital, up to 24 weeks
Length of ICU stay
Time Frame: From administration to discharge ICU, up to 24 weeks
The number of days the subject stayed in the ICU
From administration to discharge ICU, up to 24 weeks
Length of hospital stay
Time Frame: From administration to discharge hospital, up to 24 weeks
The number of days the subject stayed in the hospital
From administration to discharge hospital, up to 24 weeks
The incidence of study drug-related Lower blood pressure
Time Frame: From study drug administration to actual extubation , up to 72 hours
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
The incidence of study drug-related slow heart rate
Time Frame: From study drug administration to actual extubation , up to 72 hours
Slow heart rate: HR<40bpm for less than 1 minute or HR<60 bpm for more than 1 minute;
From study drug administration to actual extubation , up to 72 hours
The incidence of study drug-related respiratory depression
Time Frame: From study drug administration to actual extubation , up to 72 hours
Respiratory depression: RR<10 bpm or SpO2<90%
From study drug administration to actual extubation , up to 72 hours
Analysis of the cost-effectiveness between remifentanil and fentanyl
Time Frame: From study drug administration to actual extubation , up to 72 hours
cost-effectiveness
From study drug administration to actual extubation , up to 72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Southeast University, China

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Yang Yi, MD, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 10, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 12, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 11, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZDRF

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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