Pain After Abdominal Surgery
Conditions
Brief summary
A multicenter, randomized, double-blind, placebo-positive, parallel-controlled, phase Ⅲ clinical trial was conducted to investigate the efficacy and safety of RF16001 local infiltration for analgesia after total hip arthroplasty. The primary objective was to evaluate the effectiveness of local infiltration of RF16001 for injection for postoperative analgesia after total hip arthroplasty. The secondary objective was to evaluate the safety of local infiltration of RF16001 for injection for analgesia after total hip arthroplasty.
Interventions
DRUGRF16001 for injection
Before the surgical incision was closed, 30ml of 1.43% RF16001 for injection was administered by local infiltration around the incision by an unblinded physician
Before the surgical incision was closed, an unblinded physician administered 30ml 0.5% ropivacaine hydrochloride injection by local infiltration around the incision
DRUG0.9% sodium chloride injection
Before the surgical incision was closed, an unblinded physician administered 30ml 0.9% sodium chloride injection by local infiltration around the incision
Sponsors
The Third Xiangya Hospital of Central South University
National Natural Science Foundation of China
Natural Science Foundation of Hunan Province
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 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age of 18-80 years old (including boundary value), regardless of gender; 2. Unilateral total hip arthroplasty was planned under general anesthesia; 3. American Society of Anesthesiologists (ASA) grade I-III; 4. Male weight \>=50.0kg, female weight \>=45.0kg, and 18.0 kg/m2 \<= body mass index (BMI) \<= 32.0 kg/m2; 5. Understand the nature, significance, possible benefits, possible inconvenience and potential risks of the trial in detail before the trial, understand the research procedures, and sign the informed consent form in person; 6. The participants could understand the research process and the use of various scales involved in this study, communicate well with the researchers, and complete the study in accordance with the research regulations.
Exclusion criteria
1. Had undergone ipsilateral hip surgery within 1 year before randomization, had undergone contralateral hip surgery within 3 months before randomization, and planned unilateral hip revision surgery; 2. Skin infection, ulceration, or scar constitution around the planned surgical incision, and the investigator decided that it was not suitable to participate in the trial; 3. A history of severe or refractory postoperative nausea or vomiting; 4. History of myocardial infarction, unstable angina pectoris, severe arrhythmia such as atrioventricular block degree II or above, and cardiac insufficiency within the past year or currently; And not suitable to participate in the trial according to the investigator's judgment; 5. A history of ischemic stroke (except lacunar infarction with no additional safety risk) or transient ischemic attack within the previous year or currently, a history of psychiatric disorders (such as schizophrenia, depression, etc.), cognitive impairment, or epilepsy as judged by the investigator to be ineligible to participate in the trial; Or any other central nervous system or cerebrovascular disease or medical history that was deemed by the investigator to be ineligible for participation in the trial; 6. Patients who underwent total hip arthroplasty due to developmental dysplasia of the hip ⅲ-IV (Crowe classification in the Appendix), femoral neck fracture and/or intertrochanteric fracture, proximal femur or acetabular tumor and were judged by the investigator to be ineligible for the study; 7. Combined with other pain conditions that may confuse the evaluation of postoperative pain by the investigator, and was not suitable for participating in the study by the investigator; Patients who planned to undergo surgery at other sites during the study period; 8. Patients with known history of anesthesia accident or any component of the investigational drug, protocol-defined intraoperative medication, allergy or contraindication to rescue drugs and similar drugs, past history and/or family history of malignant high fever; 9. Use of any of the following drugs before randomization, except those permitted under the protocol: 1) within the 5 half-lives before randomization (subject to the actual drug instructions, if the half-life is unknown, it will be eluted according to 48h), including but not limited to: Class III antiarrhythmic drugs, glucocorticoids (intravenous or intra-joint), sedative-hypnotic agents, anxiolytic agents, antidepressant agents, strong CYP1A2 enzyme inhibitors (e.g., ciprofloxacin, enoxacin, eparylestradiol, fluvoxamine), strong CYP3A4 enzyme inhibitors (e.g., voriconazole, ketoconazole, ritonavir, clarithromycin), and sedative agents as specified in the protocol Except for prescribed use), analgesics (any opioids, non-opioids, local anesthetics (except for examination and intraoperative puncture and intubation), etc. Except if used in accordance with programme provisions); 2) successful use of Chinese herbal medicine with clear analgesic effects assessed by investigators from 7 days before signing ICF to randomization; 3) use of central alpha-adrenergic agonists (e.g., clonidine), anticonvulsants (e.g., pregabalin, gabapentin) within 14 days before randomization; 10. QTc \> 450ms in men and QTc \> 470ms in women during the screening period; Or patients with pulse \< 50 beats/min or pulse \> 100 beats/min (excluding abnormal pulse before admission to the operating room), or patients with refractory hypertension (systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg after treatment with 3 different types of antihypertensive drugs during screening, excluding abnormal blood pressure before admission to the operating room), According to the investigator's judgment, the abnormality has clinical significance. 11. The following laboratory abnormalities during screening: 1) alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 3 times upper limit of normal (ULN) and/or total bilirubin (TBIL) \> 1.5 times ULN; 2) blood urea nitrogen (BUN) and/or serum creatinine (Cre) \> 1.5 times upper limit of normal (ULN); 3) random blood glucose \> 11.1mmol/L or glycated hemoglobin A1c \> 8% in diabetic patients; 4) Prothrombin time (PT) \> upper limit of normal +3s and/or activated partial thromboplastin time (APTT) \> upper limit of normal +10s; 5) hemoglobin (Hb) \< 80g/L; Or platelet count \< 80% lower limit of normal; 12. Pregnant or lactating women; Trial participants of childbearing potential and their partners were unwilling to use contraception throughout the study; Or planned pregnancy within 3 months after the end of the study (including male trial participants); 13. A history of drug abuse and alcohol abuse within 1 year before using the investigational drug; Heavy drinking is defined as consuming more than 14 standard units of alcohol per week (1 standard unit containing 14 g of alcohol, such as 360 mL of beer or 45 mL of 40% spirits or 150 mL of wine); History of psychotropic drugs and narcotic drugs abuse; 14. Participants who participated in any clinical trial as a trial participant within 3 months before randomization (received investigational drug), except those who failed screening and did not receive any treatment; 15. Any other factors considered by the investigator to preclude participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under curve (AUC) of the pain intensity-time during 0-72h at rest | From administration until 72 hours after administration | Area under the resting pain intensity time curve (AUC0-72h) during 0-72 hours after administration. The pain intensity was evaluated using the 11-point numerical rating scale (NRS; where 0 no pain and 10 worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the pain intensity time curve at rest | From administration until 24 hours after administration, from 24 hours to 48 hours after administration, from 48 hours to 72 hours after administration | The area under the pain intensity time curve ( AUC0-24h, AUC24-48h, AUC48-72h) in resting state during 0-24h, 24-48h, and 48-72h after the completion of administration. The pain intensity was evaluated using the 11-point numerical rating scale (NRS; where 0 no pain and 10 worst possible pain). |
| Area under the pain intensity time curve during exercise | From the time of administration to 24 hours and 72 hours after administration, from 24 hours to 48 hours after administration, from 48 hours to 72 hours after administration | Area under the pain intensity time curve (AUC0-24h, AUC24-48h, AUC48-72h, AUC0-72h,) during exercise during 0-24h, 24-48h, 48-72h and 0-72h after the completion of administration. The pain intensity was evaluated using the 11-point numerical rating scale (NRS; where 0 no pain and 10 worst possible pain). |
| Cumulative use of rescue analgesics during each period | From the time of administration to 24 hours, 48 hours, 72 hours after administration, from 24 hours to 48 hours after administration, from 48 hours to 72 hours after administration | Cumulative amount of rescue analgesics used during 0-24h, 24-48h, 48-72h, and 0-72h after completion of administration. |
| The number of rescue analgesia in each period | From the time of administration to 24 hours, 48 hours, 72 hours after administration, from 24 hours to 48 hours after administration, from 48 hours to 72 hours after administration | The cumulative number of rescue analgesics used during 0-24h, 24-48h, 48-72h, and 0-72h after completion of administration |
| Time of first morphine rescue analgesia | From administration until 72 hours after administration | The time from the completion of administration to the first morphine rescue analgesic treatment |
| Proportion of rescue analgesia in each period | From the time of administration to 24 hours, 48 hours, 72 hours after administration, from 24 hours to 48 hours after administration, from 48 hours to 72 hours after administration | Proportion of participants who used rescue analgesics within 0-24h, 24-48h, 48-72h, and 0-72h after completion of administration. |
| Trial participant satisfaction and investigator satisfaction | From administration until 72 hours after administration | Satisfaction was assessed using a Likert scale (comprising five dimensions: dissatisfied, neutral, satisfied, very satisfied, and extremely satisfied). |
| Incidence of adverse events | From the time of administration to day 7 after administration | — |
Countries
China
Outcome results
None listed