Back to resultsIntravenous Lidocaine on Chronic Pain in Patients Undergoing Hepatectomy
Primary Purpose
Postoperative Chronic Pain
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Lidocaine Hydrochloride, Injectable
0.9% normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Postoperative Chronic Pain focused on measuring lidocaine
Eligibility Criteria
Inclusion Criteria:
Age: 18-80 years old American Society of Anesthesiologists(ASA) Ⅰ～III BMI≤30 Primary single hepatocellular carcinoma resection was proposed for patients undergoing laparotomy (median incision, right subcostal incision/inverted L-shaped incision)
Exclusion Criteria:
Primary liver cancer with malignant tumors of other organs (such as lung, kidney, intestine, etc.).
Primary hepatocellular carcinoma with portal vein or inferior vena cava and other large vascular thrombus.
Long-term opioid use, alcohol or drug abuse or any of the drugs (lidocaine, etc.) used in this study were contraindicated and allergic for patients.
Patients with severe hepatic and renal dysfunction (total bilirubin >1.46mg/dl, glomerular filtration rate <30ml/min /1.73㎡ or end-stage renal disease).
Severe heart disease (severe heart block (including sinoatrial, atrioventricular, and intraventricular block); Severe heart failure (ejection fraction <20%); Sinus bradycardia; Patients with Adams-Stokes syndrome, preexcitation syndrome, etc Patients with a history of uncontrolled seizures or acute porphyria. Long-term use of cimetidine and β-blockers (lidocaine metabolism is inhibited through the liver, resulting in increased blood concentration of the drug, which can lead to adverse cardiac and nervous system reactions).
Patients treated with drugs that are contraindicated with lidocaine (phenobarbital, thiopental, sodium nitroprusside, mannitol, amphotericin B, ampicillin, mesonotal, sulfadiazine sodium); Patients who are using enoxacin, lomefloxacin, norfloxacin, and prulifloxacin.
Patients with a history of gastrointestinal bleeding or perforation after nsaids;Patients with active gastrointestinal ulcers/bleeding or who have had recurrent ulcers/bleeding in the past.
Patients who had taken other experimental drugs or were participating or participating in other clinical trials within 3 months of enrollment.
Failure to cooperate with the study for any reason or the researcher considers it inappropriate to be included in the study.
Sites / Locations
- West China HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lidocaine group
Conventional analgesia group
Arm Description
General anesthesia is induced in the lidocaine group with intravenous lidocaine 1.5mg/kg for ten minutes, followed by continuous injection of lidocaine 1.5mg/kg.h. At the end of the operation, the patient controlled intravenous analgesia with lidocaine is used, and the dose of lidocaine is 30mg/kg(no more than 2000mg at most).
The lidocaine is replaced by identical volumes and rates of 0.9% saline. At the end of the operation, the patient controlled intravenous analgesia without lidocaine is used.
Outcomes
Primary Outcome Measures
The incidence of chronic pain at 3 months postoperatively
Chronic pain is defined as pain that lasts or recurs for longer than 3 months . For CPSP, it mainly refers to the pain that persists past normal healing time.Pain scoring is performed at 3 months using the Digital Evaluation Scale (NRS), with 11 digits ranging from 0 to 10 indicating the degree of pain, 0 indicating no pain, and 10 indicating severe pain. Subjects choose a number to indicate the degree of pain based on their personal pain experience.
Secondary Outcome Measures
The incidence of chronic pain at 6 months , 1 year, 3 year and 5year postoperatively
Chronic pain is defined as pain that lasts or recurs for longer than 3 months. For CPSP, it mainly refers to the pain that persists past normal healing time.Pain scoring is performed at 6 months postoperatively using the Digital Evaluation Scale (NRS), with 11 digits ranging from 0 to 10 indicating the degree of pain, 0 indicating no pain, and 10 indicating severe pain. Subjects choose a number to indicate the degree of pain based on their personal pain experience.
The levels of inflammatory factors at 24 hours after surgery
Peripheral blood NK cells, TNF-α, CXCL10, CX3CL1, cytokines IL-6, IL-8, C3a, C5a, P(CD62P)-selectin, NETosis-specific indicators (MPO and Histone H3), three tumor progressions and metastasis-related markers (VEGF-A, MMP-3, MMP-9,MMP-2) are measured 24 hours after operation.
The incidence of moderate to severe pain at 24, 48 and 72 hours after surgery at rest and during movement;
The pain is evaluated using numerical rating scale（NRS). NRS scores range from 0 to 10 points, with 0 points representing no pain, 1-3 points representing mild pain, 4-6 points representing moderate pain, 7-9 points representing severe pain and 10 points
The cumulative morphine consumption at 24, 48 and 72 hours postoperatively
Intraoperative and postoperative opioid use is reported as morphine milligram equivalents, calculated using the Practical Pain Management calculator
The incidence of a composite of postoperative pulmonary complications during
defined as positive if any component developed before discharge after surgery; These complications included respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, or aspiration pneumonitis loading dose, immediately after the end of surgery, and at the first 24 hours after surgery
Length of hospital stay
determined by the number of days from admittance to discharge
Plasma lidocaine concentration immediately after loading，after surgery and 24-hours postoperatively
Plasma lidocaine concentration is an important indicator for evaluating the safety of the drug during use.
The incidence of lidocaine toxicity within 72 hours after operation
Lidocaine toxicity mainly includes neurological manifestations such as dizziness, tinnitus, convulsions, cardiac manifestations such as bradycardia, new severe atrioventricular block and so on.
Overall survival
Overall survival is defined as the time between the date od surgery and the date of death
Recurrence-free survival
Postoperative re-examination is based on the diagnosis of enhanced CT, MRI, ultrasound or blood examination to determine whether the patient has recurrence and metastasis. Recurrence-free time refers to the time from surgery to tumor recurrence based on the above CT, MRI, etc.
accessible survival
Patient self-assessment is carried out by using the World Health Organization(WHO) Disability Scale, with a minimum score of 12 points and a maximum score of 60 points. The lower the score, the higher the quality of life
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05492669
Brief Title
Intravenous Lidocaine on Chronic Pain in Patients Undergoing Hepatectomy
Official Title
Effect of Prolonging Intravenous Lidocaine on Chronic Pain and Long-term Quality of Life in Patients Undergoing Hepatectomy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 27, 2020 (Actual)
Primary Completion Date
July 27, 2024 (Anticipated)
Study Completion Date
July 27, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a further observation and follow-up of the patients enrolled in the registration number NCT04295330 to further evaluate the effect of long-term infusion of lidocaine on postoperative chronic pain, long-term quality of life and survival rate in patients undergoing liver cancer surgery.
Detailed Description
This study is a further observation and follow-up of the patients enrolled in the registration number NCT04295330 to further evaluate the effect of long-term infusion of lidocaine on postoperative chronic pain, long-term quality of life and survival rate in patients undergoing liver cancer surgery. 272 patients with primary liver cancer who meet the inclusion criteria are included. According to the random number, the patients are divided into lidocaine group and conventional analgesia group.In the lidocaine group, a bolus injection of lidocaine 1.5 mg/kg, given as an infusion over 10 minutes, followed by a continuous infusion of lidocaine at 1.5 mg/kg per hour for the whole surgical procedure and will be discontinued at the end of surgery. Postoperative pain management during the first 72 postoperative hours will involve the use of a PCIA device, which will contain lidocaine , sufentanil , granisetron diluted to 200 mL in 0.9 % normal saline. In the placebo group, the same volume of normal saline instead of lidocaine will be administered. Blood samples will be drawn immediately after the bolus infusion of lidocaine, at the end of surgery, and 24 hours after surgery to measure plasma lidocaine concentrations. Blood samples will also be collected at 24 hours after surgery for subsequent measurement of inflammatory factors. Numeric rating scale(NRS) is used to evaluate pain at rest and light activities at postoperative 24, 48, 72 hours. The recovery time of postoperative gastrointestinal function, length of hospital stay, and the incidence of lidocaine toxicity within postoperative 72 hours will be recorded. Follow-up after discharge includes chronic pain and accessible survival at postoperative 3 months, 6 months,1 year, 3 year and 5 year, relapse-free survival and overall survival at postoperative 6 months, 1 year, 3 years and 5 years after surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Chronic Pain
Keywords
lidocaine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The experimental group received lidocaine and the control group received the same amount of saline.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The participants, the anesthesiologist, data collectors, the physicians performing the follow-up, and data analysts will be blinded to the group allocation. Blinding will maintain until the completion of the final analyses.
Allocation
Randomized
Enrollment
272 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lidocaine group
Arm Type
Experimental
Arm Description
General anesthesia is induced in the lidocaine group with intravenous lidocaine 1.5mg/kg for ten minutes, followed by continuous injection of lidocaine 1.5mg/kg.h. At the end of the operation, the patient controlled intravenous analgesia with lidocaine is used, and the dose of lidocaine is 30mg/kg(no more than 2000mg at most).
Arm Title
Conventional analgesia group
Arm Type
Placebo Comparator
Arm Description
The lidocaine is replaced by identical volumes and rates of 0.9% saline. At the end of the operation, the patient controlled intravenous analgesia without lidocaine is used.
Intervention Type
Drug
Intervention Name(s)
Lidocaine Hydrochloride, Injectable
Other Intervention Name(s)
lidocaine group
Intervention Description
In the lidocaine group, at the end of the induction of general anesthesia, a bolus injection of lidocaine 1.5 mg/kg, calculated using the patient's ideal body weight and given as an infusion over 10 minutes, followed by a continuous infusion of lidocaine at 1.5 mg/kg per hour for the whole surgical procedure and will be discontinued at the end of surgery. Postoperative pain management during the first 72 postoperative hours will involve the use of a PCIA device, which will contain lidocaine 30mg/kg, sufentanil 2 μg/kg, granisetron 12 mg diluted to 200 mL in 0.9 % normal saline.
Intervention Type
Drug
Intervention Name(s)
0.9% normal saline
Other Intervention Name(s)
placebo group
Intervention Description
In the placebo group, the same volume of normal saline will be administered during anesthesia. The postoperative PCIA device will contain sufentanil 2 μg/kg, granisetron 12 mg diluted to 200 mL in 0.9% normal saline solution with a total volume of 200 ml.
Primary Outcome Measure Information:
Title
The incidence of chronic pain at 3 months postoperatively
Description
Chronic pain is defined as pain that lasts or recurs for longer than 3 months . For CPSP, it mainly refers to the pain that persists past normal healing time.Pain scoring is performed at 3 months using the Digital Evaluation Scale (NRS), with 11 digits ranging from 0 to 10 indicating the degree of pain, 0 indicating no pain, and 10 indicating severe pain. Subjects choose a number to indicate the degree of pain based on their personal pain experience.
Time Frame
3 months postoperatively
Secondary Outcome Measure Information:
Title
The incidence of chronic pain at 6 months , 1 year, 3 year and 5year postoperatively
Description
Chronic pain is defined as pain that lasts or recurs for longer than 3 months. For CPSP, it mainly refers to the pain that persists past normal healing time.Pain scoring is performed at 6 months postoperatively using the Digital Evaluation Scale (NRS), with 11 digits ranging from 0 to 10 indicating the degree of pain, 0 indicating no pain, and 10 indicating severe pain. Subjects choose a number to indicate the degree of pain based on their personal pain experience.
Time Frame
6 months, 1 year and 3 year postoperatively
Title
The levels of inflammatory factors at 24 hours after surgery
Description
Peripheral blood NK cells, TNF-α, CXCL10, CX3CL1, cytokines IL-6, IL-8, C3a, C5a, P(CD62P)-selectin, NETosis-specific indicators (MPO and Histone H3), three tumor progressions and metastasis-related markers (VEGF-A, MMP-3, MMP-9,MMP-2) are measured 24 hours after operation.
Time Frame
24 hours postoperatively
Title
The incidence of moderate to severe pain at 24, 48 and 72 hours after surgery at rest and during movement;
Description
The pain is evaluated using numerical rating scale（NRS). NRS scores range from 0 to 10 points, with 0 points representing no pain, 1-3 points representing mild pain, 4-6 points representing moderate pain, 7-9 points representing severe pain and 10 points
Time Frame
At 3 days after surgery
Title
The cumulative morphine consumption at 24, 48 and 72 hours postoperatively
Description
Intraoperative and postoperative opioid use is reported as morphine milligram equivalents, calculated using the Practical Pain Management calculator
Time Frame
At the end of the surgery，24，48 and 72 hours after surgery
Title
The incidence of a composite of postoperative pulmonary complications during
Description
defined as positive if any component developed before discharge after surgery; These complications included respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, or aspiration pneumonitis loading dose, immediately after the end of surgery, and at the first 24 hours after surgery
Time Frame
during the period from the end of surgery to discharge
Title
Length of hospital stay
Description
determined by the number of days from admittance to discharge
Time Frame
during the period from the end of surgery to discharge
Title
Plasma lidocaine concentration immediately after loading，after surgery and 24-hours postoperatively
Description
Plasma lidocaine concentration is an important indicator for evaluating the safety of the drug during use.
Time Frame
Immediately after bolus, after surgery and 24-hour postoperatively
Title
The incidence of lidocaine toxicity within 72 hours after operation
Description
Lidocaine toxicity mainly includes neurological manifestations such as dizziness, tinnitus, convulsions, cardiac manifestations such as bradycardia, new severe atrioventricular block and so on.
Time Frame
within 72 hours after operation
Title
Overall survival
Description
Overall survival is defined as the time between the date od surgery and the date of death
Time Frame
6 months, 1 year, 3 years, 5 years postoperatively
Title
Recurrence-free survival
Description
Postoperative re-examination is based on the diagnosis of enhanced CT, MRI, ultrasound or blood examination to determine whether the patient has recurrence and metastasis. Recurrence-free time refers to the time from surgery to tumor recurrence based on the above CT, MRI, etc.
Time Frame
6 months, 1 year, 3 years, 5 years postoperatively
Title
accessible survival
Description
Patient self-assessment is carried out by using the World Health Organization(WHO) Disability Scale, with a minimum score of 12 points and a maximum score of 60 points. The lower the score, the higher the quality of life
Time Frame
3 months, 6 months, 1 year, 3 years, 5 years postoperatively
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 18-80 years old American Society of Anesthesiologists(ASA) Ⅰ～III BMI≤30 Primary single hepatocellular carcinoma resection was proposed for patients undergoing laparotomy (median incision, right subcostal incision/inverted L-shaped incision)
Exclusion Criteria:
Primary liver cancer with malignant tumors of other organs (such as lung, kidney, intestine, etc.).
Primary hepatocellular carcinoma with portal vein or inferior vena cava and other large vascular thrombus.
Long-term opioid use, alcohol or drug abuse or any of the drugs (lidocaine, etc.) used in this study were contraindicated and allergic for patients.
Patients with severe hepatic and renal dysfunction (total bilirubin >1.46mg/dl, glomerular filtration rate <30ml/min /1.73㎡ or end-stage renal disease).
Severe heart disease (severe heart block (including sinoatrial, atrioventricular, and intraventricular block); Severe heart failure (ejection fraction <20%); Sinus bradycardia; Patients with Adams-Stokes syndrome, preexcitation syndrome, etc Patients with a history of uncontrolled seizures or acute porphyria. Long-term use of cimetidine and β-blockers (lidocaine metabolism is inhibited through the liver, resulting in increased blood concentration of the drug, which can lead to adverse cardiac and nervous system reactions).
Patients treated with drugs that are contraindicated with lidocaine (phenobarbital, thiopental, sodium nitroprusside, mannitol, amphotericin B, ampicillin, mesonotal, sulfadiazine sodium); Patients who are using enoxacin, lomefloxacin, norfloxacin, and prulifloxacin.
Patients with a history of gastrointestinal bleeding or perforation after nsaids;Patients with active gastrointestinal ulcers/bleeding or who have had recurrent ulcers/bleeding in the past.
Patients who had taken other experimental drugs or were participating or participating in other clinical trials within 3 months of enrollment.
Failure to cooperate with the study for any reason or the researcher considers it inappropriate to be included in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chunling Jiang, PhD
Phone
18980601096
Email
jiang_chunling@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunling Jiang, PhD
Organizational Affiliation
West China Hospital
Official's Role
Study Director
Facility Information:
Facility Name
West China Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunling Jiang, PhD
Phone
18980601096
Email
jiang_chunling@yahoo.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intravenous Lidocaine on Chronic Pain in Patients Undergoing Hepatectomy
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