Efficacy and Safety of Oliceridine for Moderate to Severe Acute Pain After Orthopedic Surgery

The goal of this clinical trial] is to further explore the effectiveness and safety of oxelidine in the treatment of moderate to severe acute pain after orthopedic surgery. The main question it aims to answer is: Pain management after orthopaedic surgery provides more effective and safe drug options, provides new options for clinical treatment, and provides a scientific basis for clinical practice.

Participants will be asked to pain score in the different time, treatments they'll be given and use optimal drug. Researchers will compare analgesic effect of oxelidine of different dose.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Low dose oxelidine group; Drug: High dose oxelidine group; Drug: Hydromorphone group

Detailed Description

Induction and maintenance of anesthesia were the same in all patients, performed by the same anesthesiologist. The study Coordinator (Dr. He Kin Nang) used the Central randomization System software to randomly assign high-dose oxelidine fumarate (group H), low-dose oxelidine fumarate (group L) and hydromorphone (group M) in a ratio of 1:1:1. The distribution was concealed using the same opaque envelopes, which were sealed and stored in a locked cabinet, without the knowledge of the anesthesiologist and the follow-up physician.

The drugs for the study were prepared by an independent nurse anesthesiologist according to a randomized outcome code, using the drug's configuration:

Group L: oxelidine fumarate (10ml, 20mg) + 190ml normal saline diluted to 200ml, PCIA parameters were set as follows: background infusion rate was 0, self-controlled dosage was 0.35mg (3.5ml), locking time was 6min, load was 1.5mg; Group H: oxelidine fumarate (10ml, 20mg) + 190ml normal saline diluted to 200ml, PCIA parameters were set as follows: background infusion rate was 0, self-controlled dosage was 0.5mg (i.e. 5ml), locking time was 6min, load was 1.5mg; Group M: hydromorphone (6ml, 12mg) + normal saline (194ml) diluted to 200ml. PCIA parameters were set as follows: background infusion rate was 0, self-controlled dosage was 0.3mg (5ml), locking time was 6min, and load was 1mg.

The PCIA pump starts from the withdrawal of the tracheal catheter. When the patient's pain Numerical Evaluation Scale score (NRS) is ≥5, the effective pressure of the PCIA pump can be increased for 1-3 times according to the actual pain sensation. If the pain is still not relieved, the intravenous injection of hydromorphone 0.5-1mg (or drugs that can directly have a conversion relationship with morphine) can be slowly injected. The PCIA pump is stopped 48 hours after surgery. If the patient still feels pain and the NRS score is ≥5, 5-10mg of hydromorphone can be slowly injected intravenously (or drugs that can directly have a conversion relationship with morphine). In both groups, 200mg celecoxib (400mg daily) was taken orally at 08:00 and 16:00 each day from the first day after surgery (the second day of the study) as a multimodal analgesic regimen until the patients stopped the drug after no pain discomfort. If the study drug or remedial analgesic is still insufficient, the patient's study drug therapy is discontinued and the usual analgesic therapy as determined by the clinician is adopted.

Main study indicators: Area under the curve (AUC NRS-R0-72) of pain scores at rest 0-72 hours after surgery in the three groups. Pain scores 0 hours after surgery were replaced by pain scores 15 minutes after extubation.

Secondary study measures: The total amount of opioid relief analgesics converted into morphine 0-72 hours after surgery in the three groups; Three groups first used PCIA as a compression time for remedial analgesia; The area under the curve (AUCRNS-R0-72) of pain scores during exercise in the three groups at 0-72 hours after surgery was replaced by the pain scores during cough 15 minutes after extubation. NRS scores of resting and exercise at different time points in the three groups within 72 hours after operation; Duration of initial relief analgesia; 0-24h dosage of relief analgesic drugs; 0-48 hours of relief analgesia; 0-48The total number of HPCA pump presses and effective presses; The proportion of subjects who did not use remedial analgesia from 0 to 48h; Subject and investigator analgesic satisfaction scores.

Safety assessment (follow-up up to day 3) : exposure, follow-up of adverse events (AEs), respiration-related adverse events (hypoxemia, respiratory depression, hypoventilation), upper respiratory tract reactions (nausea, vomiting), drowsiness or sedation, fever, constipation, dizziness, headache, pruritus, etc.

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dongmei Ma; Phone Number: +8615267358077; Email: 8019111@zju.edu.cn
• Study Contact Backup: Name: Li Li; Phone Number: +8618267858561; Email: 65602423@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. elective orthopedic surgery under general anesthesia.
2. The patient can communicate normally and has the correct expression of pain

Exclusion Criteria:

1. Patients with advanced tumor
2. Other acute and chronic pain conditions are present
3. Severely obese (30 kg/m2)
4. Pregnant or lactating women
5. Allergy to opioids
6. Sleep apnea syndrome
7. Long-term opioid treatment
8. Patients with mental and nervous system diseases, gastrointestinal obstruction, chronic obstructive pulmonary disease or pulmonary heart disease, cardiovascular disease
9. Abnormal liver function during screening
10. Abnormal renal function during screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose oxelidine group; Oxelidine fumarate (10ml, 20mg) + normal saline 190ml diluted to 200ml. PCIA parameters were set as follows: background infusion rate was 0, self-controlled dosage was 0.35mg (3.5ml), locking time was 6min, and load was 1.5mg	Drug: Low dose oxelidine group; Analgesic dose
Experimental: high dose oxelidine group; Oxelidine fumarate (10ml, 20mg) + normal saline 190ml diluted to 200ml. PCIA parameters were set as follows: background infusion rate was 0, self-controlled dosage was 0.5mg (5ml), locking time was 6min, and load was 1.5mg	Drug: High dose oxelidine group; Analgesic dose
Active Comparator: hydromorphone group; Hydromorphone (6ml, 12mg) + normal saline (194ml) diluted to 200ml. PCIA parameters were set as follows: background infusion rate was 0, self-controlled dosage was 0.3mg (5ml), locking time was 6min, and load was 1mg	Drug: Hydromorphone group; Analgesic dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score at rest 0-72 hours after surgery	Patients' pain scores at rest were recorded from 0-72 hours after surgery.	1 h (hour), 6 h,12 h,18 h,24 h,32 h,40 h,48 h,60 h,72 h (hours) after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total amount of opioid after operation.	The total amount of opioid relief analgesics was converted into morphine after operation.	72 hours after surgery
PCIA as a remedial analgesic press time	Record the number of PCIA pump compressions (including the number of effective and ineffective compressions)	during procedure (The moment to remove the PCIA pump.)

Collaborators and Investigators

• Sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
• Investigators: Study Chair: Dongmei Ma, The Fourth Affiliated Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: KY-2024-028

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
• product manufactured in and exported from the U.S.: No