Clinical trial NCT06530563: the Efficacy and Safety of Oliceridine Fumarate Injection for Acute Pain After Abdominal Surgery
Official title: the Efficacy and Safety of Oliceridine Fumarate Injection for Acute Pain After Abdominal Surgery: a Randomized, Double-blind, Positive-drug Parallel-controlled, Multi-center Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Acute Pain
Opioid Analgesic Adverse Reaction
Keywords: Oliceridine
acute pain after surgery
abdominal surgery
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Wu Jieping Medical Foundation
First posted: 2024-07-31
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if Oliceridine fumarate injection works to treat acute pain after abdominal surgery. It will also learn about the safety of Oliceridine fumarate injection. The main questions it aims to answer are:

1. Does Oliceridine fumarate injection works to treat acute pain after abdominal surgery?
2. Does Oliceridine fumarate injection lead to less adverse effect?

Researchers will compare Oliceridine fumarate injection to a positive-drug (Sufentanil Citrate) to see if Oliceridine fumarate injection not inferior to sufentanil in the efficacy and safety for acute pain after abdominal surgery.

Participants will:

1. Receive patient controlled analgesia treat using Oliceridine or sufentanil after surgery
2. Be followed up every 6 hours until 48 hours after surgery or before discharge

Detailed description: Traditional opioid, such as morphine, sufentanil , is an important drug treatment of postoperative period of acute pain, but their use is often limited because of significant side effects, such as respiratory depression, postoperative nausea and vomiting and sedation. If a drug is effective treatment of postoperative pain and avoid these adverse reactions, it will shorten the postoperative recovery time of patients, increase patients' satisfaction, and reduce hospitalization costs. Basic research shows that traditional opioids mainly bind to μ-opioid receptors and activate G protein signal transduction to exert analgesic effect. In addition, they stimulate the recruitment of β-arrestin, leading to respiratory depression, nausea and vomiting and other side effects. Oliceridine is a newly μ-opioid receptor agonist, which mainly activates the G protein signaling pathway to exert analgesic effect, but has a weak recruitment effect on β-arrestin and thus reduces the incidence of adverse reactions. However, due to its recent introduction to the market, there is still a lack of large-scale clinical studies on the application of Oliceridine in the population. So this topic to discuss the analgesic efficacy and adverse reactions of Oliceridine in patients with acute pain after abdominal surgery. Our study hypothesized that Oliceridine would have comparable analgesic efficacy and a lower incidence of associated side effects than sufentanil.

Eligibility criteria: Inclusion Criteria:

1. Preoperative inclusion criteria 1) aged ≥18 years and ≤75 years at screening; 2) Plan to undergo open or laparoscopic surgery, and the types of surgery mainly include: Giant hysteromyoma resection, gynecologic surgery: laparotomy, laparoscopic uterine and double adnexectomy, laparoscopic removal of pelvic abscess Gastrointestinal surgery: radical resection for gastric cancer, right-sided colon cancer , transverse colon cancer or ileostomy closure surgery Renal surgery: Open or endoscopic nephrectomy or partial nephrectomy Other open or bulky abdominal lumpectomy of unknown origin; 3) able to understand and comply with research procedures and requirements, and can provide a written informed consent before any research program.
2. postoperative inclusion criteria: 1) patients who required open or laparoscopic surgery; 2) According to the investigator's judgment, the patient had recovered sufficiently from the intraoperative anesthesia protocol to accurately complete the protocol-specified questionnaire;

Exclusion Criteria:

1.preoperative exclusion criteria:

1. undergo any clinical trial within 28 days before surgery;
2. ASA grade III or above;
3. patients with advanced tumors with ascites or extensive metastasis, receiving systemic chemotherapy or radiotherapy, or requiring postoperative hyperthermic perfusion;
4. existing other acute or chronic pain conditions;
5. body mass index (BMI) \< 18 or \> 30 kg/m2;
6. during pregnancy and lactation women, or screening or surgery on the day of blood or urine pregnancy test positive; Patients or planning a pregnancy, including men;
7. opioid allergy;
8. Allergy to or contraindication to anesthesia, adjunctive analgesia, rescue analgesics, emergency antiemetics, and antibiotics used in the study;
9. with sleep apnea syndrome;
10. long-term opioid treatment was defined as receiving more than 15mg sufentanil equivalent units per day on more than 3 days per week for a period of more than 1 month in the 12 months prior to surgery;
11. preoperatively five half-life (if half-life is unknown, the 48 hours) use any painkillers; Or long-term nonsteroidal anti-inflammatory drug (NSAID) treatment, defined as more than 2 consecutive weeks of daily NSAID use in the 6 months before surgery;
12. affect drug metabolism;
13. with mental or nervous system diseases (such as epilepsy, depression, schizophrenia, etc.), gastrointestinal obstruction, chronic obstructive pulmonary disease or pulmonary heart disease, cardiovascular diseases (heart rate less than 50 beats/min, blood pressure less than 90/60 mmHg or atrioventricular block Ⅱ or above Ⅱ degree), etc.;
14. use of oral, inhaled, or parenteral corticosteroids within 3 months before surgery (nasal corticosteroids and limited topical corticosteroids were allowed at the discretion of the investigator);
15. or alcohol breath test positive urine drug screening;
16. screening of abnormal liver function (total bilirubin \> 2 x normal ceiling ULN, aspartate aminotransferase (AST) acuity 1.5 x ULN and alanine aminotransferase (ALT) or 1.5 x ULN);
17. abnormal renal function (creatinine \> 1×ULN) at screening;
18. positive for human immunodeficiency virus antibody, hepatitis B virus surface antigen or hepatitis C virus antibody or treponema pallidum antibody at screening;
19. screening between QTcF exception: men \> 450 ms, women \> 470 ms;
20. researchers think doesn't fit into the group of other conditions.

Postoperative exclusion criteria:

1. intraoperative, postoperative or anesthetic deviations that may affect the efficacy and safety evaluation in the study;
2. evidence of hemodynamic instability or respiratory insufficiency.

Primary outcomes:
measure: Area under the pain intensity time curve (AUC0-48, time in hours) in resting and moving states as assessed by numerical rating scale(NRS) at 48 hours
timeFrame: 48 hours
Secondary outcomes:
measure: Area under the pain intensity time curve (AUC) in resting and moving states as assessed by NRS at 12 and 24 hours
timeFrame: 12 or 24 hours
measure: total dose of rescue analgesics within 48 hours
timeFrame: 48 hours or the liquid of pump has run out before 48 hours.
measure: proportion of patients used rescue analgesics
timeFrame: 48 hours or when the liquid of pump has run out before 48 hours.
measure: Incidence of respiratory depression
timeFrame: 48 hours
measure: The occurrence of nausea and vomiting
timeFrame: 48 hours
measure: Condition of sedation
timeFrame: 48 hours
measure: the occurrence of adverse events
timeFrame: 1 month
measure: Satisfaction scores within 48 h of the participants and researchers
timeFrame: 48hours
Other outcomes:
measure: the analgesic effect and adverse reactions of Oliceridine in preoperative and postoperative hypertensive patients taking angiotensin-converting enzyme inhibitor/angiotensin receptor blocker(ACEI/ARB) drugs
timeFrame: 1 month
Locations:
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Xiangya Hospital of Central South University
name: e wang, doctor
role: PRINCIPAL_INVESTIGATOR
References: