Anrikefon-based Patient-controlled Intravenous Analgesia Following Laparoscopic Surgery

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Area under curve (AUC) of visceral pain intensity with movement within 48 hours [Срок оценки: Within 48 hours after intervention.]

Вторичные конечные точки (3)

• AUC of visceral pain intensity at rest within 48 hours [Срок оценки: Within 48 hours after intervention.]
• AUC of overall pain intensity with movement within 48 hours [Срок оценки: Within 48 hours after intervention.]
• AUC of overall pain intensity at rest within 48 hours [Срок оценки: Within 48 hours after intervention.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Peking University First Hospital — Пекин

Публикации

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Идентификаторы

NCT: NCT07525986 · 2025R0444-0003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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