Study on Repeat Liposomal Bupivacaine for Post-Surgery Pain in Anal Fistula Patients.

Official title

Efficacy of Repeat Dosing of Liposomal Bupivacaine on Postoperative Pain in Patients With Anal Fistula: A Multicenter, Randomized, Open-Label, Controlled Study

Overview

Anal Fistula refers to an abnormal infectious fistula tract between the anorectum and the perianal skin. The prevalence of anal fistula is approximately 8.6 cases per 100,000 individuals. It can occur at any age but is relatively more common in individuals aged 20-40 years, with a higher incidence in males than females. Postoperative wound management is a critical component of the overall treatment for anal fistula patients. Regular postoperative wound care, such as dressing changes, can reduce recurrence rates, alleviate pain, and shorten hospitalization time. However, postoperative pain remains a major challenge in wound management following anal fistula surgery. This is largely attributed to inadequate current postoperative analgesic protocols. With ongoing advancements in local anesthetics, liposomal bupivacaine has been applied for postoperative analgesia. It offers higher bioavailability and a prolonged half-life, providing up to 72 hours of sustained analgesic effect. Given the limitations of existing analgesic strategies for post-anal fistula surgery, developing more effective pain management approaches to reduce postoperative pain holds significant clinical importance. Therefore, the investigators propose that a repeat-dosing strategy based on liposomal bupivacaine may provide superior postoperative pain control for anal fistula patients. To investigate this, the investigators designed a prospective, multicenter, randomized, open-label, controlled clinical trial. This study aims to evaluate the efficacy and safety of repeat-dose liposomal bupivacaine for postoperative analgesia following anal fistula surgery, thereby generating high-level evidence to support its clinical application in this context.

Interventions

• Drug A single dose of liposomal bupivacaine is administered at the conclusion of surgery without adjunctive analgesics, followed by a supplemental dose 72 hours postoperatively.
  At surgical closure, a single dose of undiluted liposomal bupivacaine (266 mg/20 mL) is administered without concurrent analgesics. The total 20 mL volume is divided into six equal aliquots (≈3.3 mL each) and infiltrated circumferentially around the incision using a 25-gauge or larger-bore needle. Injections target tissue layers above and below the fascia and within the subcutaneous plane, with frequent aspiration during administration to mitigate intravascular injection risk. Seventy-two hours

Primary outcome measures

• Area Under the Curve (AUC) of the Numerical Rating Scale (NRS) for pain within 7 Days postoperatively (NRS-AUC0-168h) [Time frame: 7 days postoperatively]

Secondary outcome measures (12)

• Numerical Rating Scale (NRS) for pain during wound dressing changes within 7 days postoperatively [Time frame: 7 days postoperatively]
• Area Under the Curve (AUC) of the Numerical Rating Scale (NRS) for pain from 96 to 168 hours postoperatively (NRS-AUC96h-168h) [Time frame: 96 to 168 hours postoperatively]
• Number of breakthrough pain episodes and corresponding Numerical Rating Scale (NRS) scores during episodes [Time frame: 7 days postoperatively]
• Postoperative 7-day cumulative consumption of all analgesic drugs (calculated as morphine equivalents) [Time frame: 7 days postoperatively]
• Postoperative 7-day cumulative consumption of rescue analgesic drugs (calculated as morphine equivalents) [Time frame: 7 days postoperatively]
• Safety (including incidence of postoperative adverse events and serious adverse events): Adverse events and serious adverse events occurring within 14 days after medication were assessed [Time frame: 14 days after medication were assessed]
• Postoperative heart rate monitoring: Heart rate at 24h, 48h, 72h, 96h, 120h, 144h, and 168h postoperatively. [Time frame: At 24, 48, 72, 96, 120, 144, and 168 hours postoperatively.]
• Postoperative blood pressure monitoring: systolic blood pressure, and diastolic blood pressure at 24h, 48h, 72h, 96h, 120h, 144h, and 168h postoperatively. [Time frame: At 24, 48, 72, 96, 120, 144, and 168 hours postoperatively.]
• SF-12 scores at preoperative, 1 week, 1 month, and 2 months postoperatively. [Time frame: 1 week, 1 month, and 2 months postoperatively.]
• Preoperative, 14-day postoperative, and 1-month postoperative Wexner Incontinence Scores [Time frame: Prior to surgery; 14 days after surgery; 1 month postoperatively.]
• Analgesia satisfaction: Postoperative analgesic satisfaction was assessed using a 5-point categorical scale at 24h, 96h, and 168h postoperatively. [Time frame: At 24, 96, and 168 hours postoperatively.]
• Wound healing rate within 8 weeks postoperatively. [Time frame: 8 weeks postoperatively]

Eligibility criteria

Inclusion criteria

• Diagnosed with anal fistula and scheduled to undergo anal fistula surgery;
• Aged between 18 and 60 years;
• ASA (American Society of Anesthesiologists) physical status class I-II;
• Patient provides written informed consent after understanding the study protocol.

Exclusion criteria

• Anal fistula caused by specific etiologies (e.g., tuberculosis);
• Concurrent acute perianal skin infection;
• Poorly controlled diabetes (HbA1c >9%);
• Chronic use of corticosteroids;
• History of radiotherapy or chemotherapy within the past 2 weeks;
• Pregnancy or lactation;
• Hypersensitivity to local anesthetics or any component of the investigational drug;
• History of substance abuse, illicit drug use, or alcohol abuse;
• Use or planned use of non-opioid/opioid analgesics within 12 hours before/during surgery;
• Concurrent treatment with anticonvulsants, MAO inhibitors, antidepressants, neuromuscular blockers, or anticholinergics within 2 weeks prior to surgery;
• Severe hepatic/renal impairment, cardiopulmonary dysfunction, coagulation disorders, or comorbidities contraindicating surgery;
• History of severe psychiatric disorders or cognitive impairment;
• Sensory disorders (e.g., hyperalgesia) or preexisting pain interfering with postoperative pain assessment;
• Contraindications to amide-type local anesthetics, opioids, or propofol;
• Participation in investigational drug trials within 90 days prior to enrollment;
• Other clinical/laboratory conditions deemed by investigators to preclude trial participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Sixth Affiliated Hospital of Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT07081373 · 2025ZSLYEC-365

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗