Postoperative Analgesia
Conditions
Brief summary
Evaluation of safety and efficacy of Nalbuphine versus Morphine patient controlled intravenous analgesia (PCIA) for the treatment of postoperative analgesia
Interventions
PCIA，The lockout interval is set at 10 minutes, with no background infusion.
PCIA，The lockout interval is set at 10 minutes, with no background infusion.
Sponsors
Yangtze River Pharmaceutical Group Jiangsu Zilong Pharmaceutical Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-65 years (inclusive), regardless of gender. 2. Weight 45-100 kg (inclusive) and BMI 18.0-30.0 kg/m² (inclusive). 3. Preoperative ASA Physical Status Class I-III. 4. Scheduled for elective general anesthesia in abdominal surgery (single incision ≥5 cm) or orthopedic surgery (limb/joint procedures); completed anesthesia recovery within 4 hours postoperatively, with NRS score ≥4, and willingness to accept protocol-defined analgesia. 5. Ability to comprehend study objectives, operate PCIA devices, and communicate effectively with investigators. 6. Female subjects must be non-pregnant, non-lactating, and agree to use contraception (including partners) for 3 months post-study. 7. Voluntary participation with signed informed consent.
Exclusion criteria
1. Known or suspected allergy/hypersensitivity to any component of the investigational product, other opioids, or contraindicated drugs specified in the protocol . 2. Neurological/psychiatric disorders including: 1. Clinically significant neurological diseases (e.g., epilepsy, cognitive impairment) . 2. History of brain injury, increased intracranial pressure, or psychiatric disorders (e.g., schizophrenia, bipolar disorder, depression, anxiety) that may interfere with safety or study assessments as judged by the investigator . 3. Cardiovascular diseases/history: 1. Severe cardiovascular conditions (NYHA Class II or higher), myocardial infarction, angina, or severe arrhythmia within the past year . 2. Abnormal 12-lead ECG findings during screening (e.g., sinus bradycardia ≤55 bpm, ≥Grade II AV block) deemed unsuitable by the investigator . 3. Resting systolic blood pressure ≥160 mmHg or \<90 mmHg, diastolic ≥100 mmHg pre-surgery . 4. Intraoperative circulatory instability (e.g., hypotension, bradycardia) assessed as high-risk for trial continuation . 4. Respiratory disorders/history: 1. Bronchial asthma, high-risk respiratory depression conditions (e.g., severe COPD ≥GOLD 3, sleep apnea syndrome) . 2. Preoperative SpO2 \<93% (room air) or intraoperative respiratory depression/ventilatory dysfunction deemed unsafe . 5. Paralytic ileus, biliary/pancreatic diseases within 12 months before screening . 6. Major surgery within 3 months prior to screening. 7. Acute/chronic non-surgical pain interfering with postoperative pain assessment . 8. Preoperative anemia: Hemoglobin \<70 g/L or hematocrit \<25% . 9. High bleeding risk: 1. Congenital bleeding disorders (e.g., hemophilia) . 2. Platelet count \<0.75×LLN, PT \>ULN+3s, or APTT \>ULN+10s . 10. Organ dysfunction: 1. Albumin \<35 g/L (untreated) . 2. Liver/kidney function abnormalities: TBIL/ALT/AST/ALP ≥1.5×ULN ; Creatinine ≥1.5×ULN or clinically significant renal impairment; Recent dialysis (within 28 days) . 11. Random blood glucose ≥11.1 mmol/L during screening (preoperative) . 12. Participation in other clinical trials with active treatment within 3 months before surgery . 13. Other conditions deemed unsuitable by the investigator for safety or protocol compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference over 0-48 hours(SPID48) | 0-48 hours | SPID48=∑PID48×\[time in hours slapsed since the previous observation\], PID48 denotes the pain intensity difference at time 48 hours after the first administration relative to baseline. The pain intensity is rated using an 11-point numeric scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable." |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference over 0-12 hours(SPID12) | 0-12 hours | SPID12=∑PID12×\[time in hours slapsed since the previous observation\], PID12 denotes the pain intensity difference at time 12 hours after the first administration relative to baseline. The pain intensity is rated using an 11-point numeric scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable." |
| Sum of Pain Intensity Difference over 0-24 hours(SPID24) | 0-24 hours | SPID24=∑PID24×\[time in hours slapsed since the previous observation\], PID24 denotes the pain intensity difference at time 24 hours after the first administration relative to baseline. The pain intensity is rated using an 11-point numeric scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable." |
| Sum of Pain Intensity Difference over 0-32 hours(SPID32) | 0-32 hours | SPID32=∑PID32×\[time in hours slapsed since the previous observation\], PID32 denotes the pain intensity difference at time 32 hours after the first administration relative to baseline. The pain intensity is rated using an 11-point numeric scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable." |
| Total Number of PCIA Pump attempts during 0~48h | 0-48 hours | The PCIA protocol was implemented as follows: For subjects with baseline NRS scores ≥4, investigators administered the first PCIA bolus to initiate analgesia.The exact time of investigator's first PCIA activation was recorded as D0-0h. PCIA Pump Settings: Experimental Group: 2 mg per demand dose (2 mL/dose); Control Group: 1 mg per demand dose (2 mL/dose); Lockout Interval: 10 minutes. Background Infusion: None. Subsequent Analgesia Management: Following initial activation, subjects self-administered additional PCIA doses as needed based on pain levels. Subsequent PCIA Use: Subjects self-administer additional PCIA doses as needed based on pain levels. PCIA Discontinuation \& Data Collection: At 48 hours (±20 min) after the first study drug administration (or upon early withdrawal), study staff will: pause and disconnect the PCIA pump, Record: total number of PCIA presses, number of effective presses and total dosage of study drug delivered via PCIA |
| Number of Effective Deliveries during 0~48h | 0-48 hours | The PCIA protocol was implemented as follows: For subjects with baseline NRS scores ≥4, investigators administered the first PCIA bolus to initiate analgesia.The exact time of investigator's first PCIA activation was recorded as D0-0h. PCIA Pump Settings: Experimental Group: 2 mg per demand dose (2 mL/dose); Control Group: 1 mg per demand dose (2 mL/dose); Lockout Interval: 10 minutes. Background Infusion: None. Subsequent Analgesia Management: Following initial activation, subjects self-administered additional PCIA doses as needed based on pain levels. Subsequent PCIA Use: Subjects self-administer additional PCIA doses as needed based on pain levels. PCIA Discontinuation \& Data Collection: At 48 hours (±20 min) after the first study drug administration (or upon early withdrawal), study staff will: pause and disconnect the PCIA pump, Record: total number of PCIA presses, number of effective presses and total dosage of study drug delivered via PCIA |
| Total Delivered Dose during 0~48h | 0-48 hours | The PCIA protocol was implemented as follows: For subjects with baseline NRS scores ≥4, investigators administered the first PCIA bolus to initiate analgesia.The exact time of investigator's first PCIA activation was recorded as D0-0h. PCIA Pump Settings: Experimental Group: 2 mg per demand dose (2 mL/dose); Control Group: 1 mg per demand dose (2 mL/dose); Lockout Interval: 10 minutes. Background Infusion: None. Subsequent Analgesia Management: Following initial activation, subjects self-administered additional PCIA doses as needed based on pain levels. Subsequent PCIA Use: Subjects self-administer additional PCIA doses as needed based on pain levels. PCIA Discontinuation \& Data Collection: At 48 hours (±20 min) after the first study drug administration (or upon early withdrawal), study staff will: pause and disconnect the PCIA pump, Record: total number of PCIA presses, number of effective presses and total dosage of study drug delivered via PCIA |
| Time to First Use of Rescue Medication | 0-48 hours | Time to first use of rescue medication during 0\~48h.(For subjects with inadequate pain control (NRS score ≥4) who consent to rescue therapy, the following conditions must be met before administering rescue medication: 1) NRS score remains ≥4 within 5 minutes prior to rescue drug administration; 2) At least 5 minutes have elapsed since the last effective PCIA pump press, and the next PCIA bolus is not yet due) |
| Proportion of Subjects Requiring Rescue Medication | 0-48 hours | — |
| Number of Rescue Medication Administrations | 0-48 hours | — |
| Proportion of Subjects with Treatment Failure | 0-48 hours | — |
| Patient Global Impression of Change (PGIC) at 48 Hours Post-Dose | 0-48 hours | The PGIC scale (6-point) will be administered at 48h (±30min) post-dose to evaluate patients' perceived change in analgesia, ranging from 'Very much improved' (1) to 'Much worse' (6). |
Countries
China
Outcome results
None listed