Pain After Abdominal Surgery
Conditions
Brief summary
A multicenter, randomized, double-blind, placebo-positive, parallel-controlled, phase Ⅲ clinical trial of the efficacy, safety and pharmacokinetics of TRD303 solution for postoperative analgesia in patients undergoing abdominal surgery was conducted. The primary objective was to evaluate the efficacy of TRD303 solution for postoperative analgesia after abdominal surgery. The secondary objective was to evaluate the safety and pharmacokinetic profile of TRD303 solution for postoperative analgesia after abdominal surgery.
Interventions
DRUGTRD303 solution
After the peritoneum was sutured, the final irrigation and suction were performed, and the wound was smeered with TRD303 solution after incision injection before the surgical incision was sutured. The injection volume of the main incision was 2.5mL (±0.5mL was allowed according to the actual situation of the incision). For surgery involving multiple incisions, the secondary incisions were administered according to the number of incisions per unit, and the drug administration volume of each incision was 0-0.5 mL (0mL≤ administration volume ≤0.5mL).
After the completion of peritoneal suture, final irrigation and aspiration, 0.5% ropivacaine hydrochloride was injected locally around the incision before the surgical incision was closed. If there was residual drug solution after the administration of the primary incision, the residual drug solution was used to the secondary incision infiltration, and a total of 30mL was given.
After the suture of the peritoneum, final irrigation and aspiration, 0.9% sodium chloride injection was injected locally around the incision before the suture of the surgical incision. If there was residual drug solution after the administration of the primary incision, the residual drug solution was used to the secondary incision infiltration, and a total of 30mL was given.
Sponsors
The Third Xiangya Hospital of Central South University
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. Fully understand the purpose and significance of this study, voluntarily participate in this study, voluntarily sign the informed consent, and voluntarily abide by the process of this study; 2. 18 years old ≤ age ≤80 years old, regardless of gender; 18.0kg/m2≤BMI≤30.0kg/m2, ≥50.0kg for men and ≥45.0kg for women; 4\. American Society of Anesthesiologists (ASA) grade I-II (Appendix 1); (5) Elective abdominal surgery under general anesthesia, including laparoscopic or open surgery, and the length of the main incision is expected to be between 7±2cm (including the boundary value at both ends); 6. Can understand the research process and the use of various scales involved in this study, and can effectively communicate with researchers.
Exclusion criteria
1. Those who are known to have allergies or contraindications to ropivacaine or other amide local anesthetics, inactive ingredients of the investigational drug, or other drugs that may be used during the trial, and who are judged by the investigator to be unsuitable for the trial; 2. Use of the following drugs for less than 5 half-lives before randomization (according to the actual drug instructions, the half-life is unknown, or eluted according to 48 hours), including but not limited to: Class III antiarrhythmic drugs, glucocorticoids (systemic), anticonvulsants, sedative-hypnotic drugs, anxiolytic drugs, antidepressant drugs, CYP1A2 enzyme inhibitor, sedative drugs (except those used according to the protocol), analgesic drugs (except those used according to the protocol), the specific types refer to the list of prohibited drugs; Use of Chinese herbal medicine with definite analgesic effect assessed by investigators within 7 days before randomization; 3. Participants who planned to use hyperthermic perfusion, intraperitoneal chemotherapy, physical therapy, or other concomitant therapies during the treatment period that the investigator judged might affect postoperative pain; 4. patients who underwent abdominal surgery within 1 year before signing ICF; 5. patients who planned to undergo surgery at other sites during the study period; 6. Combined with other pain conditions that may confound the evaluation of postoperative pain according to the investigator; 7. Participants with a history of congenital or idiopathic methemoglobinemia or glucose-6-phosphate dehydrogenase deficiency; 8. Previous and/or family history of malignant hyperthermia; 9. Participants with poorly controlled blood pressure during screening (systolic blood pressure ≥160mmHg or ≤90 mmHg while sitting during screening, and/or diastolic blood pressure ≥100 mmHg or ≤60mmHg during screening, excluding abnormal blood pressure during anesthesia), whose abnormalities were judged by the investigator to be clinically significant and increase perioperative risk; 10. Heart rate \< 50 beats/min or heart rate \> 100 beats/min during screening (excluding abnormal heart rate during anesthesia), and the abnormal heart rate was judged by the investigator to be clinically significant; QTcF \> 450ms in men and \> 470ms in women \[QTcF=QT/ (RR\^0.33)\]; Or a history of severe arrhythmias such as atrioventricular block of degree II or higher, or cardiac insufficiency; 11. Patients with severe liver, kidney, cardiovascular, cerebrovascular, or metabolic diseases judged by the investigator to be unsuitable for the trial; 12. Patients with advanced malignant tumors who were judged by the investigators to be not suitable for participating in the trial; 13. Patients with a history of mental diseases (such as schizophrenia, depression, etc.), dementia, migraine, or epilepsy, who were judged by the investigator to be unfit for the trial; 14. Patients with skin infection, ulceration or scar constitution around the incision, judged by the investigator to be not suitable for the trial; 15. Participants with a history of psychoactive and narcotic drug abuse, drug use, and heavy drinking (i.e., drinking an average of more than 2 units of alcohol per day (1 unit =360mL of beer or 45mL of 40% liquor or 150 ml of wine) in the year before randomization;
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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the pain intensity time curve at rest | From administration until 4 hours, 6 hours, 12 hours, 24 hours, 48 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 (AUC0-4h, AUC0-6h, AUC0-12h, 0-24h, AUC0-48h, AUC24-48h, AUC48-72h) in resting state during 0-4h, 0-6h, 0-12h, 0-24h, 0-48h, 24-48h, and 48-72h after the completion of administration. |
| Area under the pain intensity time curve during exercise | From the time of administration to 12 hours, 24 hours, 48 hours, 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 (AUC0-12h, AUC0-24h, AUC0-48h, AUC0-72h, AUC24-48h, AUC48-72h) during exercise during 0-12h, 0-24h, 0-48h, 0-72h, 24-48h, and 48-72h after the 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 |
| Cumulative use of rescue analgesics during each period | From the time of administration to 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours after administration | Cumulative amount of rescue analgesics used during 0-4h, 0-6h, 0-12h, 0-24h, 0-48h, and 0-72h after completion of administration |
| The number of rescue analgesia in each period | From the time of administration to 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours after administration | The cumulative number of rescue analgesics used during 0-4h, 0-6h, 0-12h, 0-24h, 0-48h, and 0-72h after the completion of administration |
| Proportion of rescue analgesia in each period | From the time of administration to 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours after administration | Proportion of participants who used rescue analgesics within 0-4h, 0-6h, 0-12h, 0-24h, 0-48h, and 0-72h after administration |
Countries
China
Contacts
CONTACTwang, PhD
CONTACTyang, PhD
Outcome results
None listed