Compare the Effects of Remifentanil and Fentanyl on the Duration of Mechanical Ventilation of ICU Patients

Compare the Effects of Remifentanil and Fentanyl on the Duration of Mechanical Ventilation of ICU Patients: a Multi-centre, Randomized, Controlled Trial

To verify whether remifentanil is more beneficial to reduce the duration of mechanical ventilation, shorten the interval from SBT to extubation, reduce the incidence of adverse events, reduce the workload of nursing staff, reduce the dosage of sedatives and ICU hospitalization costs, shorten the length of ICU hospitalization, and reduce the short-term mortality.

Study Overview

• Status: Recruiting
• Conditions: Mechanical Ventilation
• Intervention / Treatment: Drug: Remifentanil; Drug: Fentanyl

Detailed Description

Opioids are widely used for analgesia in the ICU, of which, fentanyl and remifentanil are the most commonly used. Compared with the two analgesics, fentanyl is relatively cheap, but it is metabolised by liver. Long-term infusion makes its half-life extended, and side effects increase significantly. Respiratory depression is the most serious side effect and may lead to re-intubation and even sudden death.

Remifentanil is a strong selective μ-opioid receptor agonist, rapidly metabolized by non-specific plasma and tissue esterases into inactive metabolites; it has very short context-sensitive half-life even after prolonged infusion or in patients with organ failure. Remifentanil is easy to titrate and provides excellent analgesia: it allows higher doses administration than are normally used with traditional opioids without concerns about accumulation or delayed recovery.

This feature is helpful for patients with mechanical ventilation to weaning and extubate early. Previous studies comparing the two drugs mainly focus on short-term postoperative application, and theoretically long-term use can better reflect the pharmacokinetic advantages of Remifentanil. So we designed this study.

• Study Type: Interventional
• Enrollment (Anticipated): 254
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jian-Xin Zhou, MD; Phone Number: 861059978019; Email: zhoujx.cn@icloud.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Recruiting
      • ICU, Beijing Tiantan Hospital, Capital Medical University
      • Contact: Jian-Xin Zhou, MD; Phone Number: 861059978019; Email: zhoujx.cn@icloud.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Oral endotracheal intubation requiring mechanical ventilation; and (2) 18-85 years old; and (3) expected to require mechanical ventilation for longer than 24 hours.

Exclusion Criteria:

• (1) Deep sedation is required (PaO2/FiO2 ≤100, loss of consciousness during treatment with muscle relaxants, status epilepticus, surgery or surgical conditions require absolute immobilization, severe brain injury with intracranial hypertension, therapeutic hypothermia, etc. And other clinical assessments need to maintain RASS<-2); (2) The time of using sedatives or opioid analgesics is longer than 1 week before enrollment; (3) ICU stay ≥ 1 week before enrollment; (4) Invasive mechanical ventilation time ≥ 48 hours before enrollment; (5) According to the condition of the disease, it is estimated that mechanical ventilation will be needed for too long, such as the accumulation of respiratory muscles in peripheral neuromuscular diseases, brainstem damage and respiratory center involvement; (6) Delirium, alcohol withdrawal symptoms or mental illness or use of antipsychotic drugs; (7) Severe abnormal liver function (Child-Pugh grade C); (8) Renal insufficiency requires renal replacement therapy; (9) Surgical treatment is required during mechanical ventilation (except for minor operations, such as lumbar puncture, ventricular drainage, etc.); (10) Allergy to study drugs or other contraindications; (11) Pregnant or lactating women; (12) Has been selected for other RCT tests; (13) The patient or the legally authorized person is unwilling to participate in the trial; (14) The investigator judged that the patient was not suitable for selection (such as severe hypotension; potential disputes, etc.)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: remifentanil group; After enrollment, remifentanil will be used for analgesia. Duration of mechanical ventilation, incidences of adverse events, interval from SBT to extubation, dosages and costs of analgesics and sedatives drugs will be observed.	Drug: Remifentanil; Before infusion, remifentanil is given 0.3 g/kg slowly intravenous injection more than 60 seconds, and the initial dose is 0.025ug/kg/min. The dosage is adjusted to achieve the target depth of analgesia and sedation (CPOT < 3, RASS -2 to 1), with each change 0.025ug/kg/min and the maximum dose 0.15ug/kg/min.; Other Names: remifentanil hydrochloride
Active Comparator: fentanil group; After enrollment, fentanil will be used for analgesia. Duration of mechanical ventilation, incidences of adverse events, interval from SBT to extubation, dosages and costs of analgesics and sedatives drugs will be observed.	Drug: Fentanyl; Before infusion, fentanyl is given 0.3 g/kg slowly intravenous injection more than 60 seconds, and the initial dose is 0.025ug/kg/min. The dosage is adjusted to achieve the target depth of analgesia and sedation (CPOT < 3, RASS -2 to 1), with each change 0.025ug/kg/min and the maximum dose 0.15ug/kg/min.; Other Names: Fentanyl citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of mechanical ventilation	from the time of enrollment to successful removal from the ventilator	the end point of time is successfully transferred out of ICU or death or 28 days after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidences of adverse events	delirium, severe hypotension, severe bradycardia, constipation, chills, nausea and vomiting, muscle rigidity, accidental extubation	1) Tracheal intubation has been successfully removed; 2) Tracheal intubation has not been removed 15 days after inclusion, and the patient would be followed up for 15 days; 3) Tracheotomy and the ventilator successfully removed,whichever comes first.
the interval from SBT(Spontaneous Breathing Trial) to extubation	tracheal intubation has been successfully removed after the first SBT	the end point of time is successfully transferred out of ICU or death or 28 days after enrollment
dosages and costs of analgesic and sedative drugs	The consumption and cost of analgesic and sedative drugs in experimental group and control group	1) Tracheal intubation has been successfully removed; 2) Tracheal intubation has not been removed 15 days after inclusion, and the patient would be followed up for 15 days; 3) Tracheotomy and the ventilator successfully removed,whichever comes first.

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Study Chair: Jian-Xin Zhou, MD, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: mechanical ventilation; fentanyl; analgesia; remifentanil
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Remifentanil; Fentanyl
• Other Study ID Numbers: KY-2019-082-02

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