Anrikefon-based Patient-controlled Intravenous Analgesia After Laparoscopic Surgery

Efficacy of Anrikefon-based Patient-controlled Intravenous Analgesia for Pain Management After Laparoscopic Surgery: a Randomized, Double-blind, Active-controlled Pilot Trial

Visceral pain following laparoscopic surgery is frequently underestimated, yet it is associated with a range of adverse outcomes. Effective visceral pain management should constitute an essential component of postoperative analgesic strategies following laparoscopic procedures. However, conventional analgesic agents, including μ-opioid receptor agonists, lack specificity for visceral pain. Anrikefon, a novel selective peripheral κ-opioid receptor agonist, demonstrates unique efficacy in alleviating visceral pain with a favorable safety profile. Preliminary studies showed that a single intravenous dose of anrikefon effectively alleviates postoperative pain after abdominal surgery with a low risk of adverse effects. The investigators hypothesize that an appropriate dosing regimen of anrikefon administered via patient-controlled intravenous analgesia (PCIA) pump, as part of a multimodal analgesic strategy, can specifically target and alleviate visceral pain after laparoscopic surgery, thereby achieving comprehensive postoperative analgesia.

Study Overview

• Status: Terminated
• Conditions: Laparoscopic Surgery; Visceral Pain, Postoperative; Anrikefon; Patient-controlled Intravenous Analgesia
• Intervention / Treatment: Drug: High-dose anrikefon; Drug: Medium-dose anrikefon; Drug: Low-dose anrikefon; Drug: Morphine

Detailed Description

Approximately 50% to 90% of patients undergoing abdominal surgery experience moderate or severe acute postoperative pain, which primarily comprises somatic, visceral, and inflammatory pain components, with peak intensity typically occurring within the first 24 to 72 hours after surgery. Inadequate management of acute postoperative pain not only increases patients' suffering and impairs their sleep quality, but also increases the risk of postoperative complications, delays postsurgical recovery, prolongs hospital stay, elevates healthcare costs, and even contributes to the development of chronic neuropathic pain.

With advances in minimally invasive techniques and the widespread application of laparoscopic surgery, surgical incisions on the body surface have been significantly reduced, leading to diminished somatic pain. However, the intra-abdominal visceral injury is not necessarily reduced and can even be more substantial in this context, leading to prominent postoperative visceral pain that perioperative clinicians often underestimate. Consequently, effective management of visceral pain should be an essential component of postoperative analgesic strategies following laparoscopic procedures.

Opioids, renowned for their potent analgesic efficacy, serve as the cornerstone of perioperative acute pain management and constitute a critical element of multimodal analgesic regimens. Nevertheless, due to the sparse expression of μ-opioid receptors in visceral pain pathways and their weak modulation of visceral pain afferent signaling, the conventional μ-opioid receptor agonists, such as morphine, exhibit limited effectiveness against visceral pain. Anrikefon is a novel selective peripheral κ-opioid receptor agonist. Due to the high expression levels of κ-opioid receptors within visceral pain pathways, anrikefon exerts an unique therapeutic effect in alleviating visceral pain with a relatively low risk of adverse effects.

Preliminary studies indicate that a single intravenous dose of Anrikefon effectively alleviates pain after abdominal surgery with a low incidence of adverse effects. Additional evidence suggests that patient-controlled intravenous administration of anrikefon provides effective analgesia after orthopedic surgery without respiratory depression or other severe adverse effects. However, the appropriate dosing regimen of anrikefon for patient-controlled intravenous analgesia (PCIA) following laparoscopic surgery remains to be established.

The investigators hypothesize that administering appropriate doses of anrikefon via PCIA pump, as part of a multimodal analgesic regimen that comprises regional nerve blocks targeting somatic pain and nonsteroidal anti-inflammatory drugs (NSAIDs) targeting inflammatory pain, will specifically and effectively alleviate visceral pain following laparoscopic surgery. This pilot trial aims to explore the preliminary efficacy and optimal dosing regimen of anrikefon administered via PCIA after laparoscopic surgery, assess the feasibility of conducting a larger-scale randomized controlled trial, and provide essential parameters for sample size estimation in subsequent investigations.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged ≥ 18 years but < 75 years;
2. Scheduled to undergo elective laparoscopic gastrointestinal surgery with an expected duration of ≥1 hour;
3. The incisional pain can be covered by the transversus abdominis plane block or rectus sheath block; yet patients still require postoperative patient-controlled intravenous analgesia.

Exclusion Criteria:

1. Presence of preoperative cognitive impairment (Mini-Mental State Examination [MMSE] score < 27), or inability to communicate due to language barrier;
2. Body mass index (BMI) > 30 kg/m² or < 18 kg/m²;
3. Presence of poorly controlled or untreated comorbidities, including but not limited to the following: hypertension characterized by a resting systolic blood pressure (SBP) > 180 mmHg and/or diastolic blood pressure (DBP) > 110 mmHg, coronary artery disease with unstable angina or myocardial infarction within 6 months, heart failure rated as New York Heart Association classification ≥ III, severe chronic obstructive pulmonary disease (or in a state of acute exacerbation), severe hepatic insufficiency (Child-Pugh grade C), severe renal insufficiency (estimated glomerular filtration rate < 30 ml/min/1.73m²), or American Society of Anesthesiologists (ASA) physical status classification ≥ IV;
4. Continuous use of opioid analgesics for more than 10 days for any reason, or alcohol abuse (average daily intake of pure alcohol > 36 g) within 3 months before screening;
5. Preoperative use of opioid or non-opioid analgesics with the interval between the last administration and randomization shorter than five half-lives of the drug or the duration of drug action (whichever is longer);
6. Known allergies or contraindications to opiates or other medications that may be used in this study, such as anesthetics, antiemetics, and nonsteroidal anti-inflammatory drugs (NSAIDs);
7. Anticipated need for postoperative mechanical ventilation；
8. Other conditions that are considered unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose anrikefon group; Postoperative patient-controlled intravenous analgesia is established with anrikefon 1000 μg, diluted with normal saline to 100 ml, and programmed to administer an initial loading dose of 8 ml, followed by 4-ml boluses with a lockout interval of 10 minutes and no continuous background infusion.	Drug: High-dose anrikefon; Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises anrikefon (10 μg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.; Other Names: High-dose anrikefon-based patient-controlled analgesia
Experimental: Medium-dose anrikefon group; Postoperative patient-controlled intravenous analgesia is established with anrikefon 750 μg, diluted with normal saline to 100 ml, and programmed to administer an initial loading dose of 8 ml, followed by 4-ml boluses with a lockout interval of 10 minutes and no continuous background infusion.	Drug: Medium-dose anrikefon; Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises anrikefon (7.5 μg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.; Other Names: Medium-dose anrikefon-based patient-controlled analgesia
Experimental: Low-dose anrikefon group; Postoperative patient-controlled intravenous analgesia is established with anrikefon 500 μg, diluted with normal saline to 100 ml, and programmed to administer an initial loading dose of 8 ml, followed by 4-ml boluses with a lockout interval of 10 minutes and no continuous background infusion.	Drug: Low-dose anrikefon; Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises anrikefon (5 μg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.; Other Names: Low-dose anrikefon-based patient-controlled analgesia
Active Comparator: Morphine group; Postoperative patient-controlled intravenous analgesia is established with morphine 50 mg, diluted with normal saline to 100 ml, and programmed to administer an initial loading dose of 8 ml, followed by 4-ml boluses with a lockout interval of 10 minutes and no continuous background infusion.	Drug: Morphine; Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises morphine (0.5 mg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.; Other Names: Morphine-based patient-controlled analgesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted sum of pain intensity difference (SPID) of movement-evoked visceral pain within 48 hours	Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). Movement-evoked visceral pain intensity will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain).	Within 48 hours after intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted SPID of visceral pain at rest within 48 hours	Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). The intensity of visceral pain at rest will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain).	Within 48 hours after intervention.
Time-weighted SPID of movement-evoked somatic pain within 48 hours	Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). Movement-evoked somatic pain intensity will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain).	Within 48 hours after intervention.
Time-weighted SPID of somatic pain at rest within 48 hours	Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). The intensity of somatic pain at rest will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain).	Within 48 hours after intervention.
Time-weighted SPID of movement-evoked overall pain within 48 hours	Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). Movement-evoked overall pain intensity will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain).	Within 48 hours after intervention.
Time-weighted SPID of overall pain at rest within 48 hours	Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). The intensity of overall pain at rest will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain).	Within 48 hours after intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in hospital after surgery	Length of stay in hospital after surgery.	Up to 30 days after surgery.
Quality of recovery at 24 hours after surgery	Quality of postoperative recovery is assessed using the 15-item Quality of Recovery (QoR-15) scale, a patient-reported questionnaire that evaluates recovery after anesthesia and surgery across five domains: physical comfort, emotional state, psychological support, pain, and activities of daily living. The total score ranges from 0 to 150, with higher scores indicating better quality of postoperative recovery.	At the 24th hour after surgery.
Number of patient-controlled analgesia (PCA) attempts within 48 hours after intervention	The total count of times a patient presses the PCA button to self-administer analgesics.	Within 48 hours after intervention.
Rate of rescue analgesia within 48 hours after intervention	The proportion of patients who require supplemental analgesics.	Within 48 hours after intervention.
Patient satisfaction with postoperative analgesia at 48 hours after intervention	Patient satisfaction with postoperative analgesia will be evaluated at the 48th hour after intervention, using an 11-point Numeric Rating Scale (0 = the lowest level of satisfaction, 10 = the highest level of satisfaction).	At the 48th hour after intervention.
Subjective sleep quality on the night of surgery and the first postoperative night	Subjective sleep quality during the previous night will be assessed the next morning (between 8:00 and 10:00 am) using an 11-point Numeric Rating Scale (0 = the best sleep, 10 = the worst sleep).	From the night of surgery until the first night after surgery.
Time to first flatus and time to first defecation	Time to first flatus and time to first defecation.	Up to 30 days after surgery.
Time to first ambulation	Time to first walking on the ground after surgery.	Up to 30 days after surgery.
Incidence of postoperative complications (including all-cause mortality) within 30 days after surgery	Postoperative complications are defined as new-onset medical events that are harmful to patients' recovery and require therapeutic interventions, that is grade II or higher based on the Clavien-Dindo classification.	Up to 30 days after surgery.

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2025
• Primary Completion (Actual): February 11, 2026
• Study Completion (Actual): March 11, 2026

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Laparoscopic surgery; Patient-controlled intravenous analgesia; Visceral pain, Postoperative; Anrikefon
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nociceptive Pain; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Visceral Pain; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Morphine
• Other Study ID Numbers: 2025R0444

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