Preventive Analgesia With Anrikefon in Laparoscopic Cholecystectomy (ANIPAP)

Effect of Preventive Analgesia With Anrikefon on Postoperative Acute Pain and Rehabilitation Process in Adult Patients Undergoing Laparoscopic Cholecystectomy

This study will determine the optimal timing for Anrikefon administration. It will also assess the quality of patient recovery. Laparoscopic cholecystectomy (LC) is a routine surgical procedure. However, the incidence of acute visceral and incision pain is high, reaching 50% to 70%. This pain significantly impairs patient recovery.

Anrikefon is novel peripherally restricted κ-opioid receptor agonist. It has very low brain penetration. This property reduces central nervous system side effects and respiratory depression. Preventive analgesia blocks the transmission of nociceptive stimuli to the central nervous system. It reduces postoperative pain sensitization and intensity. Currently, research on Anrikefon for preventive analgesia in LC patients is limited. It impacts on the recovery process is not yet fully understood. This study will compare drug administration before anesthesia induction with intra-operative administration.

Participants will be assigned to one of two groups with equal probability using computer-generated random numbers. Patients in the Preventive Analgesia group will receive Anrikefon injection 15 minutes before anesthesia induction. Bridging Analgesia group is the control group. Patients in this group will receive Anrikefon immediately after the gallbladder is detached from the liver. Both groups will receive the identical drug dosage of 1 μg/kg.

Both treatment groups will receive identical care beyond the time of Anrikefon administration. All patients will undergo standardized anesthesia management. Parecoxib sodium 40 mg will be injected for rescue analgesia if NRS score > 4. We will analyze the primary, secondary, and exploratory outcome measures after surgery, aiming to explore the optimal timing of Anrikefon and its impact on the patient's recovery process.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Anrikefon for Preventive Analgesia; Drug: Anrikefon for bridging analgesia

Detailed Description

This study is a prospective, double-blinded, randomized controlled study. Adult patients (18-65 years old) who are planning to receive Laparoscopic Cholecystectomy will be enrolled into this study, and will be randomly divided according to 1:1. They will be named the preventive analgesia group and the bridging analgesia group. Primary end point is the time-weighted sum of pain intensity differences over 0-24 hours postoperatively (SPID₀-₂₄h) , which will be calculated according to the NRS scores at every time point(after surgery immediately ,15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, and 24 hours).

• Study Type: Interventional
• Enrollment (Estimated): 274
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wei Xiao, PhD; Phone Number: +8613810971299; Email: kitten15@126.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100053
      • Recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Wei Xiao; Phone Number: 8613810971299; Email: kitten15@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ASA physical status classification I-III;
2. Age 18-65 years;
3. Scheduled for elective laparoscopic cholecystectomy;
4. Voluntary signed informed consent;
5. BMI between 18-28 kg/m²;
6. No history of general anesthesia surgery within the past 3 months.

Exclusion Criteria:

1. Severe cardiovascular disease, respiratory disease, or psychiatric disorders;
2. Severe renal insufficiency;
3. Recent use of diuretics or compound medications containing diuretics;
4. Continuous use of opioid analgesics for more than 10 days within the past 3 months;
5. Use of medications with unknown half-life affecting analgesic efficacy within 14 days prior to randomization;
6. Pregnant women, lactating women, or those planning pregnancy in the near future;
7. History of hypersensitivity to study medications.

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: Preventive Analgesia Group; Patients in Preventive Analgesia Group will receive intravenous Anrikefon (1 μg/kg) at 15 minutes before anesthesia induction. Each bolus administration should be completed within 2 minutes ± 5 seconds.	Drug: Anrikefon for Preventive Analgesia; The Preventive Analgesia Group will receive intravenous Anrikefon (1 μg/kg) 15 minutes before anesthesia induction. Each bolus administration should be completed within 2 minutes ± 5 seconds.
Active Comparator: Bridging Analgesia Group; Patients in Bridging Analgesia Group will receive intravenous Anrikefon (1 μg/kg) immediately after the gallbladder is dissected from the liver bed. Each bolus administration should be completed within 2 minutes ± 5 seconds.	Drug: Anrikefon for bridging analgesia; The Bridging Analgesia Group will receive intravenous Anrikefon (1 μg/kg) immediately after the gallbladder is removed from the liver bed. Each bolus administration should be completed within 2 minutes ± 5 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time-weighted sum of pain intensity differences over 0-24 hours postoperatively of visceral pain	The time-weighted sum of pain intensity differences over 0-24 hours postoperatively (SPID₀-₂₄h) will be calculated through Numerical Rating Scale (NRS) scores. NRS scores ranges from 0 to 10 of visceral pain. It will be assessed immediately after surgery, and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, and 24 hours postoperatively. SPID₀-₂₄h will be calculated based on the NRS scores at each time point. Higher SPID₀-₂₄h will indicate better analgesic efficacy. The formula is: SPID₀-₂₄h = Σ[(Baseline NRS - NRS at time point) × Δt]. Δt represents the time interval between two consecutive assessments.	From the end of surgery to 24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time-weighted sum of pain intensity differences over 0-24 hours postoperatively of Incisional pain	The time-weighted sum of pain intensity differences over 0-24 hours postoperatively (SPID₀-₂₄h) will be calculated through Numerical Rating Scale (NRS) scores. NRS scores ranges from 0 to 10 of incisional pain. It will be assessed immediately after surgery, and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, and 24 hours postoperatively. SPID₀-₂₄h will be calculated based on the NRS scores at each time point. Higher SPID₀-₂₄h will indicate better analgesic efficacy. The formula is: SPID₀-₂₄h = Σ[(Baseline NRS - NRS at time point) × Δt]. Δt represents the time interval between two consecutive assessments.	From the end of surgery to 24 hours postoperatively
The Numerical Rating Scale scores for visceral pain and incisional pain	The Numerical Rating Scale (NRS) scores ranges from 0 to 10. NRS scores of visceral pain and incisional pain will be recorded immediately after surgery, and 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, and 24 hours postoperatively. Higher scores will indicate more severe pain.	From the end of surgery to 24 hours postoperatively
Duration of postoperative incisional pain and visceral pain	The duration from surgery completion to the timepointing when NRS score is< 3 .	From the end of surgery to 72 hours postoperatively
Total Oxycodone consumption of the postoperative analgesia pump	The consumption of Oxycodone in the patient-controlled analgesia (PCA) pump will be recorded.	From the end of surgery to 48 hours postoperatively
Total Parecoxib sodium for rescue analgesia after surgery	If patients' NRS score was greater than 4, they will receive Parecoxib for rescue analgesia. The total dose of parecoxib will be recorded.	From the end of surgery to 72 hours postoperatively
15-item Quality of Recovery scale	15-item Quality of Recovery scale (QOR-15) is used to assess postoperative recovery quality. The total score ranging from 0 to 150. Higher scores will indicate better postoperative recovery and lower scores will indicate poorer recovery.	at Day 1 and Day 3 after surgery
Recovery of gastrointestinal function	The duration from end of surgery to first flatus and first oral intake .	From the end of surgery to Day 3 after surgery
Intake, Feeling nauseated, Emesis, Exam, and Duration of symptoms scoring system score	Intake, Feeling nauseated, Emesis, Exam, and Duration of symptoms scoring system (I-FEED) . The I-FEED score will assess postoperative gastrointestinal function based on Intake, Feeling nauseated, Emesis, physical Exam, and Duration of symptoms. Total score ranges from 0 to 12. Higher scores will indicate worse postoperative nausea and vomiting (PONV) status.	24 hours, 48 hours, and 72 hours after surgery
Length of hospital stay	The duration of hospitalization will be calculated from the day of hospital admission to the day of discharge. The total number of hospital days will be recorded.	From the day of hospital admission to the day of discharge, on anverage of 3-5 days.
Rate of adverse reactions and complications	Adverse reactions will include postoperative nausea and vomitting, Constipation, Sedation, Somnolence, Respiratory Depression, Psychiatric Symptoms, Urinary Retention, Allergic Reactions, Intraoperative Awareness, Intraoperative Hypotension, Intraoperative Hypertension, Intraoperative Bradycardia, Intraoperative Tachycardia, Laryngospasm, Anaphylaxis, Postoperative Hypotension, Postoperative Hypertension, Postoperative Bradycardia, and Postoperative Tachycardia. Complications will include Arrhythmia, Cardiac Arrest, Myocardial Infarction, Myocardial Injury, Pneumonia, Cardiogenic Pulmonary Edema, Pulmonary Embolism, Delirium, Stroke, Acute Kidney Injury, Gastrointestinal Bleeding, Paralytic Ileus, Deep Vein Thrombosis and Infection.	From anesthesia induction to 72 hours after surgery
30 days mortality	any death of patients occur in 30 days after surgery	from the end of surgery to 30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the levels of IL-6, CRP, and PGE2	Blood plasma will be collected from patients at 1 day before surgery and 24 h after surgery to measure the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and prostaglandin E2 (PGE2) by ELISA	1 day before surgery and 24 hours after surgery

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Haisco Pharmaceutical Group Co., Ltd.
• Investigators: Principal Investigator: Wei Xiao, Xuanwu Hospital, Beijing; Principal Investigator: Tianlong Wang, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Laparoscopic Cholecystectomy; Visceral Pain; Postoperative Acute Pain; Anrikefon; Preventive Analgesia
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Nociceptive Pain; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Visceral Pain
• Other Study ID Numbers: Linyanshen[2026]008-002

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