Bupivacaine liposome injection for pain after single-port thoracoscopic lobectomy

Efficacy, Safety and Pharmacokinetics of Bupivacaine Liposome Injection for Paravertebral Nerve Block in the Treatment of Postoperative Pain After Thoracoscopic Surgery: a Multicenter, Randomized, Double-blind, Dose-finding, Positive Control, Phase Ⅱ Clinical Trial

This test will try a long-acting bupivacaine liposome injection given as a paravertebral nerve block to reduce pain after single-port thoracoscopic lobectomy in adults.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06529432 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study compares a liposomal bupivacaine injection with standard bupivacaine hydrochloride given as a paravertebral nerve block for adults undergoing elective single-aperture thoracoscopic lobectomy. Participants receive the nerve block at the time of surgery and are followed for postoperative pain control, safety, tolerability, and blood levels of the drug. Primary outcomes include measures of pain intensity and adverse events, and secondary assessments include human pharmacokinetics and opioid consumption. The trial is conducted at a single tertiary hospital site in Shanghai.

Who should consider this trial

Good fit: Adults aged 18 or older having elective single-port thoracoscopic lobectomy with BMI 18–30 kg/m2, ASA I–II, who can consent and follow study procedures and (if of childbearing potential) agree to required contraception and pregnancy testing are eligible.

Not a fit: Patients having other types of thoracic surgery, ASA class III or higher, BMI outside 18–30 kg/m2, pregnant or breastfeeding individuals, or those unable to attend the Shanghai study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the liposomal formulation could provide longer-lasting local pain relief after thoracoscopic lobectomy, reducing opioid needs and improving recovery.

How similar studies have performed: Liposomal bupivacaine has produced longer local analgesia and reduced opioid use in some surgical settings, but evidence is mixed and paravertebral use for thoracic lobectomy is less well established.

Eligibility criteria

Inclusion Criteria:

1. Subjects who are willing to strictly follow the clinical trial protocol to complete this study and voluntarily sign informed consent;
2. Elective surgical subjects undergoing lobectomy by single-aperture thoracoscope under general anesthesia;
3. age ≥18 years old , Male or female;
4. 18 kg/m2≤BMI≤30 kg/m2;
5. ASA Physical Status Classification I-II;
6. Female subjects of childbearing potential must agree to use contraception and refrain from egg donation from the signing of the informed consent form until 30 days after the last dose of the investigational drug. Serum or urine pregnancy tests must be negative before dosing and during the trial, and they must not be lactating. Male subjects with partners of childbearing potential must agree to use contraception and refrain from sperm donation from the signing of the informed consent form until 30 days after the last dose of the investigational drug.

Exclusion Criteria:

Participants with any of the following criteria were excluded from the study：

1. Pre-existing and combined diseases:

(1) Subjects with a history of myocardial infarction or unstable angina pectoris, or a history of severe arrhythmias such as atrioventricular block of degree II and above, or NYHA grade II and above in the 6 months before randomization; (2) Subjects with a history of ischemic stroke or transient ischemic attack (TIA); (3) Subjects with psychiatric disorders (such as schizophrenia, depression, etc.) and cognitive dysfunction; (4) Subjects with sensory disorders such as hyperalgesia; (5) Subjects with other physical pain witch may affect the evaluation of postoperative pain; (6) Subjects with airway or spinal anatomic factors caused by obstruction of ventilation, bronchiectasis, severe intraoperative thoracic adhesion, etc.

2\. Laboratory and other tests:

1. Abnormal laboratory results during screening.

   •Fasting blood glucose (FPG) ≥10.0mmol/L.

   •Abnormal liver function: aspartate aminotransferase (AST) or/and alanine aminotransferase (ALT) and/or total bilirubin (TBIL) ≥1.5×ULN.
   * Abnormal renal function: serum creatinine (Cr) ≥1.5×ULN, or dialysis subjects.
   * Abnormal coagulation function: PT\> upper normal value +3s and/or APTT \> upper normal value +10s.
   * Platelet (PLT) \<80×109/L.
   * Hemoglobin concentration (Hb) \< 70g/L.
2. Screening period heart rate \< 50 beats/min or heart rate \> 100 beats/min; 12-lead ECG QTc interval prolonged: male ≥450ms, female ≥470ms.
3. Subjects with refractory hypertension or a history of refractory hypertension before randomization.

3\. Combined drugs:

1. Subjects who allergic to or contraindicated with bupivacaine, other amide local anesthetics, and other drugs that may be used during the trial (e.g., propofol, remazolam, opioids, etc.).
2. Subjects who used any of the following drugs within 5 drug half-lives prior before randomization (drug half-lives are based on actual drug instructions, or at least 48 hours of elution if half-lives are unknown):

   * Class III antiarrhythmic drugs such as amiodarone.
   * Drugs that affect liver metabolism: strong CYP1A2 inhibitors such as ciprofloxacin, enoxacin, fluvoxamine; CYP1A2 substrates: such as theophylline, imipramine; Strong CYP3A4 inhibitors such as voriconazole, ketoconazole, Ritonavir; CYP3A4 substrates such as darunavir, Indinavir, saquinavir; Strong CYP3A4 inducers such as rifampin.
   * Intravenous or oral corticosteroids.
   * Sedative drugs: benzodiazepines (such as diazepam, flurazepam, oxazepam, cloazepine, triazolam, alprazolam, esazolam, midazolam, etc.), barbiturates, carbamazepine, phenytoin, magnesium sulfate, chloral hydrate, etc..
   * Pain relief and other drugs: Nonsteroidal anti-inflammatory drugs (aspirin is permitted for the prevention of cardiovascular events, provided it is used steadily for at least 30 days prior to randomization, Daily dose ≤100mg/ day), opioid agonists/antagonists, central alpha-adrenergic agonists (e.g. Clonidine, dexmedetomidine), anticonvulsants (e.g. Carbamazepine, pregabalin, gabapentin), antidepressants (e.g. Tricyclic, selective 5-HT reuptake inhibitors).

     4\. Others:

(1) Subjects had a history of substance abuse, drug use, and/or alcohol abuse within the 1 year prior to randomization, with alcohol abuse defined as drinking an average of more than 2 units of alcohol per day (1 unit =360mL beer or 45mL liquor with 40% alcohol or 150 ml wine); Or consume alcoholic food or drink within 24 hours before receiving the study drug.

(2) Subjects consumed excessive amounts of tea, coffee, grapefruit/grapefruit juice, grapefruit juice, caffeinated beverages (averaging more than 8 cups per day, 200 mL per cup) in the 14 days prior to randomization.

(3) Subjects who have participated in other clinical trials as subjects, and/or previously received investigational drug or device in this clinical trial within the 3 months prior to randomization.

(4) Subjects who have any other factors deemed unsuitable for participation in this trial by the investigator.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital Affiliated to Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Thea Yu

Conditions Local Analgesia Via Nerve Block