Laparoscopic SurgeryPhase 4NCT07525986
Anrikefon-based Patient-controlled Intravenous Analgesia Following Laparoscopic Surgery
A Phase 4 study testing High-dose anrikefon, Medium-dose anrikefon and Low-dose anrikefon in people with Laparoscopic Surgery and Visceral Pain, Postoperative, run by Peking University First Hospital at 4 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Laparoscopic Surgery, Visceral Pain, Postoperative, Anrikefon
- What is being tested?
- High-dose anrikefon, Medium-dose anrikefon and Low-dose anrikefon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 4 sitesChina
- Study dates
- 14 Apr 2026to Apr 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged >= 18 years but < 75 years;
- Scheduled to undergo elective laparoscopic colorectal surgery with an expected duration of >=1 hour;
- 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.
Who cannot join
- Presence of preoperative cognitive impairment (Mini-Mental State Examination [MMSE] score < 27), or inability to communicate due to language barrier;
- Body mass index (BMI) > 30 kg/m² or < 18 kg/m²;
- 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;
- 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;
- 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);
- 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);
- Anticipated need for postoperative mechanical ventilation；
- Other conditions that are considered unsuitable for study participation.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China4 sites, 4 recruiting
- Recruiting
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Chun-Qing Li, MD, 8610 83575138, lichuntsing@163.com
- Not yet recruiting
Beijing Friendship Hospital, Capital Medical Universit
Beijing, Beijing Municipality, 100050
Zhaoting Meng, 86 10 63138780, 526589053@qq.com
- Not yet recruiting
Hunan Provincial People's Hospital
Changsha, Hunan, 410005
Yixun Tang, 86 0731 83928286, tangyixun1024@163.com
- Not yet recruiting
The Eighth Affiliated Hospital, Sun Yat-sen University
Shenzhen, Guangdong, 518033
Yue Peng, 86 0755 83982222, 3662624240@qq.com
About this study
Official title: Efficacy of Anrikefon-based Patient-controlled Intravenous Analgesia for Pain Management After Laparoscopic Surgery: a Randomized, Double-blind, Active-controlled Pilot Tria
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.
Read the 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.
- Conditions
- Laparoscopic Surgery, Visceral Pain, Postoperative, Anrikefon, Patient-controlled Intravenous Analgesia
- Being tested
- High-dose anrikefon, Medium-dose anrikefon, Low-dose anrikefon, Morphine
- Keywords
- Laparoscopic surgery, Visceral pain, Postoperative, Anrikefon, Patient-controlled intravenous analgesia
- Medical subject headings
- Visceral Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose anrikefonDrug
Also called High-dose anrikefon-based patient-controlled analgesia
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.
Medium-dose anrikefonDrug
Also called Medium-dose anrikefon-based patient-controlled analgesia
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.
Low-dose anrikefonDrug
Also called Low-dose anrikefon-based patient-controlled analgesia
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.
MorphineDrug
Also called Morphine-based patient-controlled analgesia
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.
| Study group | Role | What they receive |
|---|---|---|
| High-dose anrikefon group | Experimental | 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. Receives: Drug: High-dose anrikefon |
| Medium-dose anrikefon group | Experimental | 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. Receives: Drug: Medium-dose anrikefon |
| Low-dose anrikefon group | Experimental | 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. Receives: Drug: Low-dose anrikefon |
| Morphine group | Active comparator | 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 Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under curve (AUC) of visceral pain intensity with movement within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Visceral pain intensity with movement will be assessed at 0, 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).
Measured: Within 48 hours after intervention.
Secondary outcomes (3)
AUC of visceral pain intensity at rest within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Visceral pain intensity at rest will be assessed at 0, 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).
Measured: Within 48 hours after intervention.
AUC of overall pain intensity with movement within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Overall pain intensity with movement will be assessed at 0, 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).
Measured: Within 48 hours after intervention.
AUC of overall pain intensity at rest within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Overall pain intensity at rest will be assessed at 0, 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).
Measured: Within 48 hours after intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2026
- Study start14 Apr 2026
- Primary completionMar 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Laparoscopic SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dong-Xin Wang, Peking University First Hospital
- Investigators
- Dong-Xin Wang, MD, PhD, Principal investigator, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07525986
- Sponsor's protocol ID
- 2025R0444-0003
- Status last verified
- Oct 2026
- First submitted
- 6 Apr 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shao R, Wang HY, Ruan ZR, Jiang B, Yang DD, Hu Y, Xu YC, Yang JT, Gao W, Zhao WY, Yan M, Lou H. Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers. Basic Clin Pharmacol Toxicol. 2024 Dec;135(6):743-754. doi: 10.1111/bcpt.14094. Epub 2024 Oct 13.
PubMed 39397291Zhong Y, Xu Y, Lei Q, Yang M, Wang S, Hu X, Xie H, Li Y, Qin Z, Gu Z, Zhang J, Wang Y, Wu J, Wang H, Ming Y, Xia Z, Zhai H, Jiang K, Zhang P, Wang Z, Wang L, Li L, Cheng Z, Jiang H, Wang G, Chen J, Zhao Z, Chen X, Yan M. HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials. Nat Commun. 2025 May 24;16(1):4830. doi: 10.1038/s41467-025-60013-y.
PubMed 40413233Wang X, Gou X, Yu X, Bai D, Tan B, Cao P, Qian M, Zheng X, Wang H, Tang P, Zhang C, Ye F, Ni J. Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch. Front Pharmacol. 2021 Nov 16;12:773204. doi: 10.3389/fphar.2021.773204. eCollection 2021.
PubMed 34867403Beck TC, Hapstack MA, Beck KR, Dix TA. Therapeutic Potential of Kappa Opioid Agonists. Pharmaceuticals (Basel). 2019 Jun 20;12(2):95. doi: 10.3390/ph12020095.
PubMed 31226764Waldhoer M, Bartlett SE, Whistler JL. Opioid receptors. Annu Rev Biochem. 2004;73:953-90. doi: 10.1146/annurev.biochem.73.011303.073940.
PubMed 15189164Ehrlich AT, Kieffer BL, Darcq E. Current strategies toward safer mu opioid receptor drugs for pain management. Expert Opin Ther Targets. 2019 Apr;23(4):315-326. doi: 10.1080/14728222.2019.1586882. Epub 2019 Mar 15.
PubMed 30802415Jiang Z, Zhou G, Song Q, Bao C, Wang H, Chen Z. Effect of Intravenous Oxycodone in Combination With Different Doses of Dexmedetomdine on Sleep Quality and Visceral Pain in Patients After Abdominal Surgery: A Randomized Study. Clin J Pain. 2018 Dec;34(12):1126-1132. doi: 10.1097/AJP.0000000000000645.
PubMed 30134283Koh JC, Kong HJ, Kim MH, Hong JH, Seong H, Kim NY, Bai SJ. Comparison of Analgesic and Adverse Effects of Oxycodone- and Fentanyl-Based Patient-Controlled Analgesia in Patients Undergoing Robot-Assisted Laparoscopic Gastrectomy Using a 55:1 Potency Ratio of Oxycodone to Fentanyl: A Retrospective Study. J Pain Res. 2020 Sep 4;13:2197-2204. doi: 10.2147/JPR.S264764. eCollection 2020.
PubMed 32943912Ruiz-Tovar J, Garcia A, Ferrigni C, Duran M. Application of Vitamin E Acetate on Staple Lines and Anastomoses of Roux-en-Y Gastric Bypass: Impact on Postoperative Pain and Acute Phase Reactants. Obes Surg. 2020 Aug;30(8):2988-2993. doi: 10.1007/s11695-020-04635-9.
PubMed 32342266Blichfeldt-Eckhardt MR, Ording H, Andersen C, Licht PB, Toft P. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy. Pain. 2014 Nov;155(11):2400-7. doi: 10.1016/j.pain.2014.09.019. Epub 2014 Sep 22.
PubMed 25250720Choi JB, Kang K, Song MK, Seok S, Kim YH, Kim JE. Pain Characteristics after Total Laparoscopic Hysterectomy. Int J Med Sci. 2016 Jul 5;13(8):562-8. doi: 10.7150/ijms.15875. eCollection 2016.
PubMed 27499688Golzari SE, Nader ND, Mahmoodpoor A. Underlying Mechanisms of Postoperative Pain After Laparoscopic Surgery. JAMA Surg. 2016 Mar;151(3):295-6. doi: 10.1001/jamasurg.2015.3934. No abstract available.
PubMed 26535957Kendall GP. Visceral pain. Br J Surg. 1985 Sep;72 Suppl:S4-5. doi: 10.1002/bjs.1800721304. No abstract available.
PubMed 3899257Sikandar S, Dickenson AH. Visceral pain: the ins and outs, the ups and downs. Curr Opin Support Palliat Care. 2012 Mar;6(1):17-26. doi: 10.1097/SPC.0b013e32834f6ec9.
PubMed 22246042Cheong JY, Keshava A, Witting P, Young CJ. Effects of Intraoperative Insufflation With Warmed, Humidified CO2 during Abdominal Surgery: A Review. Ann Coloproctol. 2018 Jun;34(3):125-137. doi: 10.3393/ac.2017.09.26. Epub 2018 Jun 30.
PubMed 29991201