Effect of Esketamine on Abdominal Pain During TACE-HAIC in Patients With Hepatocellular Carcinoma (TACE-HAIC)

Effect of Esketamine on Abdominal Pain During TACE-HAIC in Patients With Hepatocellular Carcinoma: a Prospective Study TACE-HAIC (Transcatheter Arterial Chemoembolization Combined With Hepatic Artery Infusion Chemotherapy )

Previous studies have confirmed that limb pain caused by oxaliplatin chemotherapy is related to spinal cord central sensitization - induced hyperalgesia through oxaliplatin activating spinal cord NMDA receptor(N-methyl-D-aspartic acid receptor). The investigators speculate that this may be the same as the mechanism of severe abdominal pain caused by HAIC(Hepatic Artery Infusion Chemotherapy) during oxaliplatin infusion. The analgesic effect of Esketamine is mainly related to its inhibition of NMDA receptor in spinal cord. Therefore, this study hypothesized that Esketamine can inhibit the sensitization of spinal cord center by inhibiting NMDA receptor, so as to alleviate severe abdominal pain during HAIC perfusion, and reduce abdominal pain caused by ischemia and inflammation by TACE(transcatheter arterial chemoembolization) by improving organ perfusion and anti-inflammatory effect, Therefore, it is expected that Esketamine can better alleviate acute severe abdominal pain caused by TACE-HAIC (transcatheter arterial chemoembolization combined with Hepatic Artery Infusion Chemotherapy )treatment than sufentanil, decrease the dosage of opioids, and reduce the incidence and degree of chronic abdominal pain after treatment.

Study Overview

• Status: Recruiting
• Conditions: Pain; Hepatocellular Carcinoma; Transarterial Chemoembolization; Hepatic Arterial Infusion Chemotherapy
• Intervention / Treatment: Drug: Esketamine; Drug: Sufentanil

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Recruiting
      • The Second Affiliated Hospital, Chongqing Medical University
      • Contact: Guangyou Duan, MD; Phone Number: (+86)18323376014; Email: duangy@hospital.cqmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participate in this study and sign informed consent
• Voluntarily receive postoperative intravenous controlled analgesia
• Patients receiving TACE-HAIC treatment
• HCC (hepatocellular carcinoma)patients with primary liver cancer BCLC(Barcelona Clinic Liver Cancer) stage B and C, liver function A
• Age 18 to 80

Exclusion Criteria:

• Patients who were unable to cooperate or refused to participate in the trial
• Pregnant women
• Patients with sensory abnormalities such as diabetes neuropathy
• Patients with or having a history of serious mental disorders
• Patients with poorly controlled or untreated hypertension (arterial hypertension, resting systolic / diastolic blood pressure more than 180/100mg)
• Patients with unstable angina pectoris or myocardial infarction within 6 months or congestive heart failure
• Patients with intracranial hypertension or glaucoma
• Patients with hyperthyroidism without treatment or insufficient treatment
• Patients with severe respiratory dysfunction
• Allergy or existing contraindication to chemotherapeutic drugs, opioids or ketamine drugs
• Can not follow with the study procedure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine-PCIA(patient controlled intravenous analgesia); PCIA formula：100ml analgesic solution was prepared by adding 2.5 mg/kg Esketamine and 8mg ondansetron into normal saline.	Drug: Esketamine; PCIA formula：100ml analgesic solution was prepared by adding 2.5 mg/kg Esketamine and 8mg ondansetron into normal saline. 30min before TACE treatment, the first dose of 2ml was slowly injected intravenously. No obvious adverse reactions were observed for 10min. After that, the intravenous analgesia pump was started. Parameter setting of intravenous analgesia pump: the total volume is 100ml; The duration is 2ml / h; The single dose is 2ml each time; The limit quantity is 10ml / h; The locking time was 10min and the analgesia lasted for 48h. The target value of analgesia in this study was NRS (Numerical Rating Scale)< 4; If NRS ≥ 4, when the effect is still poor after adding drugs by pressing the analgesic pump, the investigators will give the remedial drug(dolantin 50mg im st) according to the patient's condition.; Other Names: patient controlled intravenous analgesia
Active Comparator: Sufentanil-PCIA(patient controlled intravenous analgesia); PCIA formula：100ml analgesic solution was prepared by adding 2 μ g/kg sufentanil and 8mg ondansetron into normal saline.	Drug: Sufentanil; PCIA formula：100ml analgesic solution was prepared by adding 2 μ g/kg sufentanil and 8mg ondansetron into normal saline. 30min before TACE treatment, the first dose of 2ml was slowly injected intravenously. No obvious adverse reactions were observed for 10min. After that, the intravenous analgesia pump was started. Parameter setting of intravenous analgesia pump: the total volume is 100ml; The duration is 2ml / h; The single dose is 2ml each time; The limit quantity is 10ml / h; The locking time was 10min and the analgesia lasted for 48h. The target value of analgesia in this study was NRS (Numerical Rating Scale)< 4; If NRS ≥ 4, when the effect is still poor after adding drugs by pressing the analgesic pump, the investigators will give the remedial drug(dolantin 50mg im st) according to the patient's condition.; Other Names: patient controlled intravenous analgesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum pain intensity in the first 3 hours of HAIC treatment	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)	From the beginning of HAIC treatment to 3 hours after HAIC treatment
Pain intensity at 1 hour after HAIC treatment	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)	From the beginning of HAIC treatment to 1 hour after HAIC treatment
Pain intensity at 2 hours after HAIC treatment	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)	From 1 hour to 2 hours after HAIC treatment
Pain intensity at 3 hours after HAIC treatment	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)	From 2 hours to 3 hours after HAIC treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of analgesic pump compressions	When the patients felt pain, the patient controlled analgesia pump can be pressed once	From the beginning of HAIC treatment to 48 hours after HAIC treatment
Analgesic consumption	Analgesic consumption is assessed by the total amount of pain remedy with dolantin when the analgesic effect is poor after pressing analgesic pump for 3 times or more	From the beginning of HAIC treatment to 48 hours after HAIC treatment
Pain intensity at 8 hours after HAIC treatment	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)	From 7 hours to 8 hours after HAIC treatment
Pain intensity at 16 hours after HAIC treatment	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)	From 15 hours to 16 hours after HAIC treatment
Pain intensity at 24 hours after HAIC treatment	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)	From 23 hours to 24 hours after HAIC treatment
Pain intensity at 32 hours after HAIC treatment	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)	From 31 hours to 32 hours after HAIC treatment
Pain intensity at 40 hours after HAIC treatment	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)	From 39 hours to 40 hours after HAIC treatment
Pain intensity at 48 hours after HAIC treatment	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)	From 47 hours to 48 hours after HAIC treatment
Pain intensity on the seventh days after HAIC treatment	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)	From 7 days to 8 days after HAIC treatment
Pain intensity On the 14th day after HAIC treatment	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)	From 13 days to 14 days after HAIC treatment
Pain intensity on the 21st after HAIC treatment	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)	From 20 days to 21 days after HAIC treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ramsay Sedation score at 1 hour after HAIC treatment	Ramsay Sedation score is assessed by: Grade 1 (soberness- the patient is anxious, uneasy or irritable)、 Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)、 Grade 3 (soberness- the patient only responds to commands)、 Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)、 Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From the beginning of HAIC treatment to 1 hour after HAIC treatment
Ramsay Sedation score at 2 hours after HAIC treatment	Ramsay Sedation score is assessed by: Grade 1 (soberness- the patient is anxious, uneasy or irritable)、 Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)、 Grade 3 (soberness- the patient only responds to commands)、 Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)、 Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From 1 hour to 2 hours after HAIC treatment
Ramsay Sedation score at 3 hours after HAIC treatment	Ramsay Sedation score is assessed by: Grade 1 (soberness- the patient is anxious, uneasy or irritable)、 Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)、 Grade 3 (soberness- the patient only responds to commands)、 Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)、 Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From 2 hours to 3 hours after HAIC treatment
Ramsay Sedation score at 8 hours after HAIC treatment	Ramsay Sedation score is assessed by: Grade 1 (soberness- the patient is anxious, uneasy or irritable)、 Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)、 Grade 3 (soberness- the patient only responds to commands)、 Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)、 Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From 7 hours to 8 hours after HAIC treatment
The quality of sleep on the fist day after HAIC treatment	The Richards-Campbell Sleep Questionnaire (RCSQ) is assessed by the quality of patients' sleep quality.0~25 points indicate poor sleep quality;76~100 points indicate good sleep quality (0-100, 0 represents the worst sleep quality; 100 represents the best sleep quality ;higher scores mean a better outcome)	From the ending of HAIC treatment to 1 day after HAIC treatment
The quality of sleep on the second day after HAIC treatment	The Richards-Campbell Sleep Questionnaire (RCSQ) is assessed by the quality of patients' sleep quality.0~25 points indicate poor sleep quality;76~100 points indicate good sleep quality (0-100, 0 represents the worst sleep quality; 100 represents the best sleep quality ;higher scores mean a better outcome)	From 1 day to 2 days after HAIC treatment
The quality of sleep on the third day after HAIC treatment	The Richards-Campbell Sleep Questionnaire (RCSQ) is assessed by the quality of patients' sleep quality.0~25 points indicate poor sleep quality;76~100 points indicate good sleep quality (0-100, 0 represents the worst sleep quality; 100 represents the best sleep quality ;higher scores mean a better outcome)	From 2 days to 3 days after HAIC treatment
Adverse reaction	Adverse reaction is recorded according to follow-up visits after HAIC treatment	From the beginning of HAIC treatment to 72 hours after HAIC treatment
Degree of satisfaction	Degree of satisfaction is assessed by patient using numerical rating scale (0-10, 0 represents unsatisfactory; 10 represents complete satisfaction;higher scores mean a better outcome)	From the beginning of HAIC treatment to 24 hours after HAIC treatment

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University
• Investigators: Principal Investigator: Huang yan, MD, The Second Affiliated Hospital, Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): April 30, 2023

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: June 9, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Abdominal Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Psychotropic Drugs; Antidepressive Agents; Adjuvants, Anesthesia; Esketamine; Sufentanil
• Other Study ID Numbers: pain during TACE-HAIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual participant data for this study is available from the sponsor on reasonable request through email.
• IPD Sharing Time Frame: Within one year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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