Efficacy and Safety of Oxycodone Hydrochloride for Long-term Analgesia in ICU Patients

Efficacy and Safety of Oxycodone Hydrochloride and Remifentanil for Long-term Analgesia During Invasive Mechanical Ventilation in Postoperative Patients: A Pilot Study

The goal of this clinical trial is to learn if oxycodone hydrochloride works to manage pain in patients requiring mechanical ventilation. It will also assess the safety of oxycodone hydrochloride. The main questions it aims to answer are:

1. Does oxycodone hydrochloride effectively lower the CPOT (Critical Care Pain Observation Tool) score in mechanically ventilated patients?
2. What medical problems do participants have when using oxycodone hydrochloride? Researchers will compare oxycodone hydrochloride to remifentanil to see if oxycodone works better to manage pain in these patients.

Participants will:

• Receive either oxycodone hydrochloride injection at a dose of 0.03-0.2 mg/kg/h or remifentanil injection at a dose of 2-9 μg/kg/h.
• Have their pain scores assessed every 15 minutes until the CPOT score is less than 3. After reaching the target pain score, assessments will be done every 4 hours.
• Have their vital signs and monitoring data recorded.
• Have analgesia and sedation scores recorded from days 1 to 7 after administration, with drug dosages adjusted based on pain scores.
• Have the incidence of adverse reactions and changes in gastrointestinal function observed and recorded from days 1 to 7 after administration.
• If extubated within 7 days, relevant data will be collected based on the time of extubation.
• Be followed up on day 28 through the electronic medical record system to gather data on the extubation success rate and incidence of complications within the 28-day period.

Study Overview

• Status: Not yet recruiting
• Conditions: Analgesia; Mechanical Ventilation; Remifentanil; Postoperative; Oxycodone
• Intervention / Treatment: Drug: Oxycodone Hydrochloride; Drug: Remifentanil

Detailed Description

This study is a single-center, single-blind, randomized controlled exploratory study involving subjects aged 18 to 80 who are expected to require mechanical ventilation for ≥24 hours and who were intubated and received mechanical ventilation for less than 3 days before enrollment. Subjects will be treated with either oxycodone hydrochloride injection or remifentanil injection and will be randomly assigned in a 1:1 ratio, giving each subject a 50% chance of being assigned to the control group.

Trial Group: Subjects will receive oxycodone hydrochloride injection at a dose of 0.03-0.2 mg/kg/h. Pain scores will be assessed every 15 minutes until the CPOT (Critical Care Pain Observation Tool) score is less than 3. After achieving the target pain score, pain scores will be assessed every 4 hours.

Control Group: Subjects will receive remifentanil hydrochloride injection at a dose of 2-9 μg/kg/h. Pain scores will be assessed every 15 minutes until the CPOT score is less than 3. After achieving the target pain score, pain scores will be assessed every 4 hours.

During this period, the vital signs and monitoring data of the subjects will be recorded. Analgesia and sedation scores will be recorded from days 1 to 7 after administration, and the analgesic and sedative drug dosages will be adjusted based on the subjects' pain scores. Additionally, the incidence of adverse reactions and changes in gastrointestinal function will be observed and recorded from days 1 to 7 after administration.

There are no biological detection indicators in this study; all evaluations are made by the researchers through scoring sheets and will not affect the subjects' normal treatment. If a subject is extubated and weaned off the ventilator within 7 days, relevant data will be collected based on the time of extubation. On the 28th day after administration, doctors will follow up via the electronic medical record system to gather data on the extubation success rate, incidence of complications, and other relevant indicators within the 28-day period.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yunhang Zhang; Phone Number: 19542814786; Email: zhang.yunhang@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • ZhongShan Hospital FuDan University
      • Contact: Yunhang Zhang; Phone Number: 19542814786; Email: zhang.yunhang@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 ≤ Age ≤ 80
• Intubated and mechanically ventilated < 3 days prior to enrollment
• Expected need for continuous mechanical ventilation ≥ 24 hours

Exclusion Criteria:

• Patients requiring deep sedation (e.g., mechanical ventilation patients with severe man-machine dyssynchrony, respiratory distress due to severe respiratory failure, application of neuromuscular blockers, status epilepticus, surgical procedures requiring strict immobilization, mild hypothermia treatment, etc.);
• Chronic kidney disease, severe liver dysfunction (Child-Pugh Class C)
• Severe shock requiring norepinephrine ≥ 0.5 µg/kg/min
• American Society of Anesthesiologists (ASA) Class 5 patients (near death)
• Nerve injury or organic pathological changes in the brain
• Need for designated sedatives or anesthetics other than study drug during treatment
• Patients with chronic pain, frequently taking strong opioids, such as morphine
• History of alcohol or drug abuse
• Participation in other opioid studies within 30 days
• Pregnant or lactating women
• Patients with study drug allergy and contraindications Patients who are not suitable for inclusion in the study as judged by the investigator

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: Oxycodone Hydrochloride; Continuous infusion therapy	Drug: Oxycodone Hydrochloride; Oxycodone hydrochloride will be administered at a continuous infusion dose of 0.03-0.2 mg/kg/h.
Active Comparator: Remifentanil; Continuous infusion therapy	Drug: Remifentanil; Remifentanil will be administered at a continuous infusion dose of 2-9 μg/kg/h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time with Critical care Pain Observation Tool (CPOT) < 3 without rescue analgesia within 7 days of mechanical ventilation.	By CPOT Form.	Mechanical ventilation within 7 days after administration of analgesics.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days without mechanical ventilation	Collect relevant data by case form	Within 28 days after administration
Successful extubation rate	Defined as not using non-invasive or invasive mechanical ventilation within 48 hours after the first spontaneous breathing trial (SBT) in 28 days	Within 28 days after administration
Ventilator-associated pneumonia	Assessed according to diagnostic criteria	Within 28 days after administration
Delirium	Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). The CAM-ICU provides a binary outcome: the presence or absence of delirium. The assessment results in either a positive or negative diagnosis for delirium, where a positive result indicates the presence of delirium and a worse outcome for the patient.	Within 28 days after administration
Length of Stay (LOS) in ICU	Collect relevant data by case form	From ICU admission to ICU discharge (typically within 1 to 4 weeks)
Change in gastrointestinal function within 7 days of dosing	Gastrointestinal Failure (GIF) score. The score ranges from 0 to 4, a higher GIF score signifies a more severe gastrointestinal dysfunction and a worse outcome for the patient.	Postdose 1, 2, 3, 4, 5, 6, 7 days
Adverse Event (AE) incidence rate	Investigator assessment by observation	7 days postdose

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Ming Zhong, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Remifentanil; Analgesia; ICU; Mechanical Ventilation; Pilot Study; Oxycodone; oxycodone hydrochloride; long term analgesic
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil; Oxycodone
• Other Study ID Numbers: B2024-161R

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