The Effects of Oxycodone Versus Sufentanil on Pain and Inflammatory Response After TACE

• ClinicalTrials.gov Identifier: NCT06041425
• Recruitment Status: Completed
• First Posted: September 18, 2023
• Last Update Posted: February 28, 2024
• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Information provided by (Responsible Party): The First Affiliated Hospital with Nanjing Medical University

Study Description

Brief Summary:

The purpose of this randomized, double-blind trial was to compare the effects of preemptive Oxycodone and sufentanil at the same dose on pain and inflammatory response after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma. To study the effect of single dose intravenous injection of Oxycodone and sufentanil before TACE on inflammatory reaction after TACE; And (ii) evaluate the effects of different opioid drugs on pain and nausea/vomiting after TACE.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma; Transcatheter Arterial Chemoembolization; Pain; Inflammation	Drug: Oxycodone; Drug: Sufentanil	Phase 4

Detailed Description:

Transcatheter arterial chemoembolization (TACE) is currently considered as the treatment for unresectable hepatocellular carcinoma (HCC). Due to sudden blockage of the main blood vessels supplying the tumor, local liver tissue swells and the tumor rapidly necroses. A large number of inflammatory mediators, including white blood cell (WBC) count, C-reactive protein (CRP) and Interleukin 6 (IL-6), will inevitably appear in TACE induced ischemic and/or necrotic tissue reactions, which contribute to the development of pain. Pain can worsen the patient's quality of life, prolong hospital stay, and increase costs. 93% of patients require opioid therapy during and after TACE.

Opioids are the most common drugs for treating pain. There are three types of opioid receptors, μ Receptors κ Receptors and δ Receptors. Sufentanil is a highly selective drug μ Receptor agonists have fast onset and strong analgesic effects. However, sufentanil is not as effective as Oxycodone in relieving visceral pain. Oxycodone not only activates μ receptors, also occupying κ receptors, alleviate visceral ischemic pain and inflammatory reactions.

In addition to the type of medication, the administration time can also affect perioperative pain. Preemptive analgesia refers to the intervention of pain relief before nociceptive stimuli to suppress the progression of stress states and central sensitization.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effects of Single Dose Oxycodone Versus Sufentanil on Pain and Inflammatory Response After Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: a Randomized Controlled Study
• Actual Study Start Date: August 7, 2023
• Actual Primary Completion Date: December 17, 2023
• Actual Study Completion Date: December 25, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oxycodone; The patients were given 0.1mg/kg oxycodone 15 minutes before transcatheter arterial chemoembolization (TACE).	Drug: Oxycodone; The patients were given 0.1mg/kg oxycodone 15 minutes before transcatheter arterial chemoembolization (TACE). WBC count, neutrophil percentage, CRP, and IL-6 were used as inflammatory markers and measured before TACE (1 day before TACE) and 24 hours after TACE. Assess pain and side effects during TACE and within 24 hours after TACE. Pain was evaluated using the 11 point Numeric Rating Scale (NRS).; Other Name: preemptive analgesia
Active Comparator: Sufentanil; The patients were given 0.1μg/kg sufentanil 15 minutes before transcatheter arterial chemoembolization (TACE).	Drug: Sufentanil; The patients were given 0.1μg/kg sufentanil 15 minutes before transcatheter arterial chemoembolization (TACE). WBC count, neutrophil percentage, CRP, and IL-6 were used as inflammatory markers and measured before TACE (1 day before TACE) and 24 hours after TACE. Assess pain and side effects during TACE and within 24 hours after TACE. Pain was evaluated using the 11 point Numeric Rating Scale (NRS).; Other Name: preemptive analgesia

Outcome Measures

Primary Outcome Measures :

1. Intraoperative pain intensity during TACE. [ Time Frame: Intraoperative (From the beginning of TACE to the end of TACE.) ]
   Pain intensity is assessed by numerical rating scale pain scores (0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome).
2. Pain intensity at 1hour after the end of TACE. [ Time Frame: From 0 to 1 hour after the end of TACE. ]
   Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome).
3. Pain intensity at 6hours after the end of TACE. [ Time Frame: From 1hour to 6 hours after the end of TACE. ]
   Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome).
4. Pain intensity at 12hours after the end of TACE. [ Time Frame: From 6hours to 12 hours after the end of TACE. ]
   Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome).
5. Pain intensity at 24hours after the end of TACE. [ Time Frame: From 12 hours to 24 hours after the end of TACE. ]
   Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome).

Secondary Outcome Measures :

1. The WBC count [ Time Frame: 24 hours ]
   The WBC count in 10^9/L. Inflammatory reactions
2. Neutrophil percentage [ Time Frame: 24 hours ]

   neutrophil percentage in %.

   Inflammatory reactions

3. Level of CRP [ Time Frame: 24 hours ]

   CRP in mg/L.

   Inflammatory reaction

4. Level of IL-6 [ Time Frame: 24 hours ]

   IL-6 in pg/mL.

   Inflammatory reaction

5. Nausea and vomiting scale [ Time Frame: 24 hours ]
   Nausea and vomiting were graded on a four-point scale, 0,no nausea.1,mild nausea. 2,severe nausea requiring antiemetics. and 3, retching and/or vomiting.)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥18 years;
• Presence of histologically confirmed or clinically diagnosed hepatocellular carcinoma (fulfilling the criteria for lesions with typical imaging);
• Presence of Child-Pugh class A or B disease;
• Absence of benefit from a treatment of established efficacy such as resection and local ablation;
• ECOG:0-2.

Exclusion Criteria:

• Extrahepatic metastasis and/or microvascular invasion;
• Severe liver and kidney dysfunction;
• Uncontrolled or significant cardiovascular disease; Autoimmune hepatitis; Long term use of opioids, steroid hormones, and non steroidal anti-inflammatory drugs; Abnormal elevation of C-reactive protein (CRP); Increased white blood cells (>11000/mm3); Study Drugs allergy; Patients who were treated within 4 weeks after COVID-19 infection was diagnosed.

Contacts and Locations

Locations

China, Jiangsu

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China, 210029

Sponsors and Collaborators

The First Affiliated Hospital with Nanjing Medical University

Investigators

• Study Chair: Yu CHEN, MD; The First Affiliated Hospital with Nanjing Medical University

More Information

• Responsible Party: The First Affiliated Hospital with Nanjing Medical University
• ClinicalTrials.gov Identifier: NCT06041425
• Other Study ID Numbers: 2023-SR-093
• First Posted: September 18, 2023
• Last Update Posted: February 28, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The individual participant data for this study is available from the sponsor on reasonable request through email.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: August 2023 to August 2024
• Access Criteria: Within one year

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Inflammation; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pathologic Processes; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Sufentanil; Oxycodone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adjuvants, Anesthesia; Anesthetics, Intravenous; Anesthetics, General; Anesthetics