Effect of Preventive Analgesia with Oxycodone and Parecoxib Sodium on the Chronification of Acute Post-operative Pain (AOPC)

Exploring the Effect of Preventive Analgesia with Oxycodone and Parecoxib Sodium on the Chronification of Acute Pain in Adult Patients Underwent Laparoscopic-assisted Abdominal Major Surgery

The goal of this clinical trial is to learn if the administration of oxycodone for preventive analgesia works to reduce the chronification of acute postoperative pain in adult participants undergoing major abdominal surgery. The main question it aims to answer is:

• Does administration of oxycodone before surgical incision reduce the occurrence of chronic pain or relieve the chronic pain symptoms 3 months after the operation? Researchers will compare oxycodone + parecoxib sodium to placebo + parecoxib sodium combinations to see if oxycodone works to reduce the chronification of acute postoperative pain.

Participants will:

• Take oxycodone + parecoxib sodium or placebo + parecoxib sodium combinations before the surgical incision
• Cooperate with the follow-up staffs and complete some checkups or tests within 3 months after the operation.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Pain, Postoperative; Oxycodone
• Intervention / Treatment: Drug: oxycodone and parecoxib sodium combinations; Drug: Placebo and parecoxib sodium combinations

Detailed Description

Preventive analgesia encompasses a range of analgesic strategies designed to mitigate hyperalgesia and allodynia induced by noxious stimuli by preventing peripheral and intraoperative sensitization to pain. It constitutes a fundamental component of multimodal analgesia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are presently the most frequently employed agents for preventive analgesia, demonstrating efficacy in reducing the incidence of acute postoperative pain and chronic post-surgical pain. However, the management of acute postoperative pain and chronic post-surgical pain remains suboptimal. κ-opioid receptors are regarded as the primary receptors involved in the transmission of visceral pain, and κ-receptor agonists have been shown to effectively inhibit this transmission. Administering κ-receptor agonists via intravenous infusion either before the conclusion of surgery or postoperatively can substantially mitigate pain during the recovery period. This indicates that κ-receptor agonists possess potential as preventive analgesics. However, there is currently a paucity of high-quality clinical evidence supporting their use in preventive analgesia. Oxycodone functions as a dual agonist of μ-opioid and κ-opioid receptors and is extensively utilized in postoperative analgesia and anesthesia induction. Its safety and efficacy in pain management have been thoroughly validated. Theoretically, the concurrent administration of oxycodone and NSAIDs, which mitigate pain signal transmission through distinct mechanisms, could result in an additive preventive analgesic effect. However, there is currently a paucity of high-quality clinical evidence supporting this hypothesis. Consequently, this study seeks to investigate the effects of the combined administration of oxycodone and NSAIDs as preventive analgesia on the transition of acute postoperative pain to chronic pain in patients undergoing major abdominal surgery. The findings aim to contribute clinical evidence and theoretical insights to enhance perioperative pain management strategies.

• Study Type: Interventional
• Enrollment (Estimated): 1316
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luo Ailin; Phone Number: 86-027-83665480; Email: alluo@hust.edu.cn
• Study Contact Backup: Name: Li Shiyong

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ASA I~III；
• BMI ranging from 18 to 28 kg/m²；
• For elective laparoscopic-assisted major abdominal surgery under general anesthesia;
• Estimated surgical duration (from incision to the last suture of the skin) was at least 2 hours.

Exclusion Criteria:

• Pregnant or lactating patients;
• Patients diagnosed with septic shock or multiple organ failure within 14 days;
• Patients with preoperative severe electrolyte disorders;
• Patients with stroke, transient ischemic attack, or other similar events within the past 3 months
• Patients with unstable angina, myocardial infarction within the past 3 months; or presence of untreated arrhythmia or arrhythmia not well-controlled with treatment;
• Patients with diabetes, uncontrolled blood glucose levels, or diabetes complications such as diabetic ketoacidosis, hyperosmolar coma, diabetes-related infections, diabetic nephropathy, retinopathy, diabetic cardiomyopathy, diabetic peripheral neuropathy, diabetic foot, etc. before the surgery;
• Patients with severe liver dysfunction (Child-Pugh score > 6), renal dysfunction (GFR < 90 ml/(min•1.73m²));
• Exploratory surgeries, day surgeries, or surgeries that only involve opening and closing the abdomen;
• Blood pressure ≥180/110 mmHg at rest (≥Grade 3 hypertension according to the 2020 ISH Hypertension Guidelines); or systolic blood pressure <90 mmHg or mean blood pressure <65 mmHg;
• Patients participated in other drug trials within the past 3 months;
• Patients with communication difficulties, inability to understand pain scores or patient-controlled intravenous analgesia;
• Patients with consciousness disorders or other psychiatric illnesses;
• Patients with a confirmed or suspected history of substance abuse or long-term use of anesthetic sedatives and analgesics;
• Cancer patients have received neoadjuvant treatment or chemotherapy preoperatively;
• Allergic to the drugs used in this trial and their components.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OP group; Participants in this group will receive oxycodone and parecoxib sodium before surgical incision.	Drug: oxycodone and parecoxib sodium combinations; Participants will receive 0.1ml/kg oxycodone (1mg/ml) and 2 ml parecoxib sodium (20 mg/ml) combinations after the anesthesia induction but before the surgical incision. Oxycodone is administered 5 minutes after parecoxib sodium administration.
Placebo Comparator: PP group; Participants in this group will receive a placebo and parecoxib sodium before surgical incision.	Drug: Placebo and parecoxib sodium combinations; Participants will receive 0.1ml/kg placebo (0.9% saline) and 2 ml parecoxib sodium (20 mg/ml) combinations after the anesthesia induction but before the surgical incision. Placebo is administered 5 minutes after parecoxib sodium administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visceral pain scores in the surgical area at 90 days postoperatively.	The pain scores will be assessed by the Numeric Rating Scale (NRS) and Brief Pain Inventory Scale-Short form (BPI-9). The NRS evaluates pain intensity on a 0-10 scale and the scores are grouped as no (NRS 0), mild (NRS 1-4), moderate (NRS 5-7), or severe pain (NRS 8-10). The BPI-9 is a 9-item questionnaire and each item is scored from 0 = no pain to 10 = worst pain. The BPI-9 is used to assess various aspects of pain severity and pain interference.	90 days after the surgery
The incidence of moderate to severe visceral pain at 90 days postoperatively.	The incidence will be calculated as the ratio of the number of participants with moderate to severe visceral pain to the number of participants allocated to each group at 90 days after the surgery .	90 days after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Somatic pain scores in the surgical area at 48 hours postoperatively;	The pain scores will be assessed by the NRS and BPI-9 scales as described above.	48 hours after the surgery
Visceral pain scores in the surgical area at 48 hours postoperatively;	The pain scores will be assessed by the NRS and BPI-9 scales as described above.	48 hours after the surgery
Incidence of moderate to severe visceral pain at 48 hours postoperatively;	The incidence will be calculated as the ratio of the number of participants with moderate to severe visceral pain to the number of participants allocated to each group at 48 hours after the surgery.	48 hours after the surgery
Incidence of moderate to severe visceral pain in the surgical area at 30 days postoperatively;	The incidence will be calculated as the ratio of the number of participants with moderate to severe visceral pain to the number of participants allocated to each group at 30 days after the surgery.	30 days after the surgery
Incidence of moderate to severe somatic pain in the surgical area at 30 days postoperatively;	The incidence will be calculated as the ratio of the number of participants with moderate to severe somatic pain to the number of participants allocated to each group at 30 days after the surgery.	30 days after the surgery
Incidence of moderate to severe somatic pain in the surgical area at 90 days postoperatively.	The incidence will be calculated as the ratio of the number of participants with moderate to severe somatic pain to the number of participants allocated to each group at 90 days after the surgery.	90 days after the surgery

Collaborators and Investigators

• Sponsor: Ailin Luo
• Collaborators: Jinhua Central Hospital; Qujing first people's Hospital; Minda Hospital of Hubei Minzu University; Taihe Hospital of Traditional Chinese Medicine
• Investigators: Principal Investigator: Luo Ailin, Department of Anesthesiology of Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Estimated): December 9, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Oxycodone; Preventive analgesia; Chronification of acute postoperative pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative; Chronic Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Analgesics, Opioid; Narcotics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Oxycodone; Parecoxib
• Other Study ID Numbers: TJ-IRB202411042

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